Solvent-free condensation of phenylacetonitrile and nonanenitrile with 4-methoxybenzaldehyde: Optimization and mechanistic studies

Article abstract of DOI:10.1039/b418156e

The condensation of phenylacctonitrile with 4-methoxybenzaldehyde can he carried out by two solvent-free methods: i) using neat powdered KOH at room temperature with equivalent amounts of aldehyde, nitrile and base for 3 min, and ii) using K₂CO₃ in the presence of a phase transfer agent for 3 min under microwave activation or conventional heating. By extending the reaction time up to 10 min, four different products were obtained from phenyl or nitrile group migration. With nonanenitrile, only the second method could be applied to give two kinds of condensed compounds with or without phenyl (or nitrile) group migration. The intervention of non-thermal MW-specific effects was proved in some cases and interpreted. The Royal Society of Chemistry 2005.

Full text of DOI:10.1039/b418156e

View Article Online / Journal Homepage / Table of Contents for this issue
A R T I C L E
Solvent-free condensation of phenylacetonitrile and nonanenitrile
with 4-methoxybenzaldehyde: optimization and mechanistic studies
Andre´ Loupy,*a Miche`le Pellet,b Alain Petita and Giang Vo-Thanha
a Laboratoire des Re´actions Se´lectives sur Supports, ICMMO, CNRS UMR 8615,
Baˆtiment 410, Universite´ Paris-Sud, 91405, Orsay cedex, France
b Laboratoire des Carbocycles, ICMMO, CNRS UMR 8615, Baˆtiment 420, Universite´
Paris-Sud, 91405, Orsay cedex, France
Received 2nd December 2004, Accepted 9th February 2005
First published as an Advance Article on the web 17th March 2005
The condensation of phenylacetonitrile with 4-methoxybenzaldehyde can be carried out by two solvent-free methods:
i) using neat powdered KOH at room temperature with equivalent amounts of aldehyde, nitrile and base for 3 min,
and ii) using K2CO3 in the presence of a phase transfer agent for 3 min under microwave activation or conventional
heating. By extending the reaction time up to 10 min, four different products were obtained from phenyl or nitrile
group migration. With nonanenitrile, only the second method could be applied to give two kinds of condensed
compounds with or without phenyl (or nitrile) group migration. The intervention of non-thermal MW-specific effects
was proved in some cases and interpreted.
methoxybenzaldehyde 1, phenylacetonitrile 2 and finely ground
base. The main product was the a,b-unsaturated nitrile 3, occa-
sionally accompanied by compound 4 resulting from Michael
addition of 2 to 3 (eqn. (1)).
Introduction
Unsaturated nitriles play a key role in many of the pathways
proposed for the prebiotic synthesis of biological molecules.1
Arylacrylonitriles are important synthons for the synthesis
of several biologically active molecules in the preparation of
perfumes,2 flavonoid pigments,3 sexual pheromones4 and vita-
min A.5 They are directly involved in increasing soybean yield
as plant growth regulators,6 and as inhibitors of prostaglandin
synthetase.7 Recently, they have been used within the area of
organic materials for the obtention of high electron affinity
polymers which can be used to manufacture light-emitting
diodes (LEDs) with air-stable electrodes.8,9
The traditional preparation of arylacrylonitriles involves the
reaction of aromatic aldehydes with arylacetonitriles (Meyer
and Frost reaction).10 Thus, they can be obtained under basic
(1)
conditions in a polar solvent (NaOH, KOH, NaOEt or K2CO3
The influence of the nature of the base was first checked at
in MeOH, EtOH or THF)11–15 or under liquid–liquid phase-
room temperature (Table 1) and then under MW irradiation us-
transfer catalysis conditions.3,16
ing a monomode reactor21 with accurate control of temperature
The replacement of organic solvents, which inevitably lead
and MW power (Table 2).
to solvent emission and/or waste, is nowadays one the most
It is noticeable that the simplest reaction using KOH for
important goals in green chemistry.17,18 The environmentally
3 min at r.t. led to a very high yield (Table 1, entry 7). These
friendly goal of making organic compounds without using sol-
condensation reactions proceed very efficiently in the absence
vents has come several steps closer in recent years and, as stated
of solvent, as shown in some aldolization–condensations.20,22
by D. C. Dittmer:17 “The day may be coming when more drastic
Using weaker bases (Table 1, entries 1–6), yields were very low
restrictions on solvent pollution will require the adoption of no-
and reactions appeared to stop (similar results obtained in 10 or
solvent reaction conditions”. Two solvent-free syntheses have
60 min with K2CO3, Table 1, entries 1 and 2). Some amounts of
been reported in the literature: i) by J. G. Verkade et al.15 using
the Michael reaction by-product 4 were characterized (Table 1,
a tricyclic non-ionic strong Lewis base, and ii) by D. Villemin
entries 5 and 8).
et al.19 working with supported bases on inorganic solids (e.g.
Under MW irradiation, with KOH as the base, the yield (3E +
KF–Al2O3) in “dry media” under microwave (MW) irradiation.
3Z) rose to 99% with a higher purity: yield and conversion values
Encouraged by the results obtained by Toda et al.20 for
are rather similar and no traces of 4 were detected (Table 2, entry
solvent-free aldolizations, we have studied here various solvent-
6). Other available bases such as Cs2CO3 and KF/Al2O3 afforded
free conditions according to the nature of the base, the presence
excellent yields (Table 2, entries 4 and 5). In the case of K2CO3
of a phase transfer agent and, if necessary, MW activation. To
and K3PO4 (Table 2, entries 2 and 3), yields could presumably
this end, we have chosen to optimize conditions for the rep-
be optimized by extending the reaction time.
resentative condensation of 4-methoxybenzaldehyde (because
of its lower reactivity) with phenylacetonitrile (an aromatic
compound) and nonanenitrile (an aliphatic one).
Phase-transfer catalysis23,24
. When the reactions were per-
formed using K2CO3, KOH or Cs2CO3 as the base, TBAB
(n-Bu4N+ Br−), TDA-1 (tris[2-(2-methoxyethoxy)ethyl]amine)25,
Aliquat 336 (mainly MeNOct3+ Cl−) or 18-crown-6 (18-C-6) as
the phase-transfer agent (PTA), five different products were
Results and discussion
Reaction with phenylacetonitrile
1
Non-catalyzed solvent-free conditions. Reactions were car-
ried out as a slurry of equivalent amounts (10 mmol) of 4-
obtained (eqn. (2)). Their structures were assigned by H and
13C NMR spectroscopy. The main results are given in Table 3.
1 5 3 4
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 5 3 4 – 1 5 4 0
T h i s j o u r n a l i s
T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 5
©

View Article Online
Table 1 Effect of the base nature on the reaction depicted in eqn. (1) at room temperature
Yields (%)b
Entry
Base (1 equiv.)
K2CO3
Reaction time/min
Conversionab (%)
3Z
3E
4
1
2
3
4
5
6
7
8
10
60
10
10
10
3
4
5
3
14
39
60
95
90
trc
5
tr
10
23
28
86
73
0
0
0
0
0
0
K3PO4·3H2O
Cs2CO3
KF/Al2O3
tr
tr
tr
1
tr
6
13
2
d
NaOH
KOH
KOCH3
3
3
tr
4
a Conversion based on phenylacetonitrile consumption. b Conversions and yields were evaluated by GC using an internal standard (diethyl phthalate).
c Traces were detected by GC. d KF/Al2O3 = 2 : 3 w/w.
Table 2 Effect of the base nature on the reaction depicted in eqn. (1) under MW irradiation
Yields (%)c
Entry
Base (1 equiv.)
K2CO3
Reaction time/min
Finala temperature /◦C
Conversionbc (%)
3Z
3E
1
2
3
4
5
6
5
30
3
3
3
2
110
131
161
145
142
117
4
44
31
93
95
99
4
43
30
90
0
1
1
3
5
3
K3PO4·3H2O
Cs2CO3
KF/Al2O3
KOH
90
96 (95)d
a Final temperature at the end of MW irradiation was measured with an optical fibre. b Conversion was based on consumption of 2. c Conversions
and yields were evaluated by GC using an internal standard (diethyl phthalate). d Isolated yield is given in brackets.
Table 3 Effects of the base and nature of the PTA on the reaction depicted in eqn. (2) in dry media under MW irradiation (10 mmol scale)
Yields (%)c
Base
PTA
Reaction time/min
Finala temperature/◦C
Conversionbc (%)
3Z
3E
5
6
7
K2CO3
TBAB
TBAB
TBAB
Aliquat
TDA-1
18-C-6
TBAB
TBAB
3
10
30
10
10
10
3
133
151
173
137
137
139
156
148
93
98
98
98
84
100
100
100
89 (78)d
40
39
34
73
30
27
33
1
1
2
1
3
1
1
1
4
0
0
22
20
20
1
22
20
23
16
19
15
0
18
18
20
21
20
18
0
18
17
20
KOH
Cs2CO3
3
a Final temperature at the end of MW irradiation measured with an optical fibre. b Conversion was based on consumption of 2. c Conversions and
yields were evaluated by GC using an internal standard (diethyl phthalate). d Isolated yield was given in brackets.
exposure) was added. After◦10 min under MW we obtained, at
a final temperature of 105 C, mainly product 3Z (88 : 0 : 2 :
3 : 0 for products 3Z : 3E : 5 : 6 : 7). It is consequently clear
that, for short reaction times and relatively low temperatures, 3Z
was the predominant product, whereas mixtures were obtained
under harsher conditions.
Comparison of microwave irradiation vs. conventional heating.
In order to check the possible intervention of specific non-
thermal MW effects,26,27 the same reactions were performed
inside a thermostatted oil bath under identical conditions
(vessel, medium, temperature, reaction time, etc.). The main
(2)
results are given in Table 4.
Specific non-thermal MW effects only appeared in two cases,
which correspond to the less reactive systems, either using a
weak base (K2CO3) in the absence of PTA (Table 4, entry 1,
conversion 31% for MW, 16% for D) or under PTC conditions
in the presence of n-heptane (Table 4, entry 6, conversion 93%
for MW, 42% for D).
In all other cases, employing a stronger base (Table 4, entries
2 and 3) or with a weak one in the presence of PTA–K2CO3
(Table 4, entry 4), excellent yields were obtained (≥94%). They
are similar whatever the mode of activation (Table 4, entries 2–5,
Using potassium carbonate/TBAB, after a very short irradi-
ation time (3 min) and at a final temperature of 133 ◦C, mainly
3Z was formed. By extension of the reaction time up to 10
or 30 min, we obtained a mixture of 3Z + 3E + 5 + 6 + 7.
Whatever the conditions of base or catalyst (except with TDA-1),
rather similar mixtures of products were obtained with constant
composition.
In order to keep the reaction temperature at around 100 ◦C,
1 mL of n-heptane, a non-polar solvent (i.e. transparent to MW
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 5 3 4 – 1 5 4 0
1 5 3 5

View Article Online
Table 4 Comparison of MW vs. conventional heating (D) under similar sets of conditions for the reaction depicted in eqn. (2) (10 mmol scale)
Yields (%)b
Activation mode Reaction time/min Temperature/◦C Conversiona (%) 3Z 3E
Entry
Base
5
6
7
1
2
3
4
5
6
K2CO3
MW
D
MW
D
MW
D
MW
D
15
15
2
2
3
3
3
3
129
131
117
115
142
141
133
128
151
145
104
98
31
16
99
95
95
95
93
86
98
98
93
42
27
16
96
89
90
90
89
81
40
40
88
37
1
0
3
3
5
0
1
4
1
2
0
0
0
0
0
0
0
0
4
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
KOH
KF/Al2O3
K2CO3 + TBAB
K2CO3 + TBAB
MW
D
10
10
7
22 16 21
20 18 20
2
0
K2CO3 + TBAB/n-heptane MW
3
0
0
0
D
7
a Conversions and yields were evaluated by GC using an internal standard (diethyl phthalate). b Conversions and yields were evaluated by GC using
an internal standard (diethyl phthalate).
for which yields and conversions are roughly the same) within
very short reaction periods (2–3 min).
1) the base-promoted b-elimination of HCN leading to alkyne
9,32,33
The importance of the specific MW effect observed here is
consistent with the previous assessment that the effect is greater
when the difficulty of the reaction is increased26–28 (i.e. higher
values of activation energy). When the transition states lie
further along the reaction coordinate they are more prone to
develop extended polarity, and consequently MW effects are
more pronounced. Here, it is the case with the less reactive
system involving K2CO3 for 15 min at 130 ◦C (conversion 31%
for MW, 16% for D) or dilution of K2CO3/TBAB in heptane (a
non-polar, i.e. MW-transparent solvent) inducing extension of
reaction time and decrease in temperature (no solvent: 3 min,
128–133 ◦C, MW, conversion 93% for MW, 86% for D; heptane:
7 min, 98–104 ◦C, conversion 93% for MW, 42% for D).
Presumably, the intervention of specific MW effects is masked
at elevated temperature29–31 which yet induces very good yields
under conventional heating. These effects could be observed
when the reaction was performed at lower temperature, as shown
for instance when n-heptane was added to the K2CO3–TBAB
system (Table 4, entries 5 and 6).
2) the [2 + 2] cycloaddition of 3 to alkyne 9, presumably with
formation of cyclobutadiene 10 after elimination of HCN,
3) the opening of 10 by two pathways (a and b), giving access
to alkynes 9, 11 and 12,
4) the nucleophilic addition of CN− to these alkynes,34 leading
to 3, 7, 5 and 6 respectively.
Unfortunately, attempts to isolate intermediates or to trap
them by more reactive alkynes failed. On the other hand, the
intermediate 9 could be synthesized by Sonogashira coupling
as reported in the literature.35 However, no formation of 3
or 7 was observed by addition of CN−, derived from KCN
or Bu4NCN, into the reaction medium under phase-transfer
catalysis conditions. Moreover, attempts to perform the [2 + 2]
cycloaddition between 9 and 3 failed.
Reaction with nonanenitrile
We subsequently studied the behaviour of a long chain aliphatic
nitrile (nonanenitrile 13), to the best of our knowledge never
studied in the literature. Only two isolated cases of aliphatic
nitriles were described: i) the base-catalyzed condensation of ace-
tonitrile with carbonyl compounds using KOH in CH3CN (act-
ing both as reagent and solvent), giving access to aliphatic a,b-
unsaturated nitriles,36–38, and ii) the condensation of RCH2CN
(R = H, C2H5) with several aldehydes and ketones using lithium
alkylamides in HMPA39 which led to b-hydroxynitriles.
We therefore extended the previous methods to the case of 13.
In the absence of any PTA, we only obtained products from the
Cannizzaro reaction (14) and hydrolysis of the nitrile (15) when
using KOH for 3 min at 133 ◦C under MW irradiation (eqn. (4)).
Mechanistic considerations
The obtention of the compounds 5–7 in the transformation of
3 at temperatures higher than 120 ◦C in the presence of a base
and a PTA is shown in Table 5.
This reaction is specific to the nitrile moiety as no reaction
occurred when using the corresponding ethyl ester 8 (eqn. (3)).
(3)
Radical mechanisms can be excluded as similar products
and yields were obtained in the presence of a radical inhibitor
(benzoquinone) and a promoter (benzoyl peroxide), or even by
carrying out the reaction in the dark.
Finally, in order to justify the formation of products 5–7
from 3, one could propose a multi-step mechanism (Scheme 1)
involving:
(4)
Table 5 Conversion of 3Z under different conditions in 10 min at 130 ◦C under MW irradiation
Reagents
3Z (%)
3E (%)
5 (%)
6 (%)
7 (%)
3Z + K2CO3
97
91
38
3
7
1
0
0
18
0
0
15
0
0
20
3Z + TBAB
3Z + K2CO3 + TBAB (0.1 equiv.)
1 5 3 6
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 5 3 4 – 1 5 4 0

View Article Online
Scheme 1 Proposed multi-step mechanism for the reaction depicted in eqn. (2).
On the other hand, when a PTA was added, two condensation
products 16 and 17 were obtained, each as E and Z isomers
(eqn. (5)).
the one proposed for phenylacetonitrile (eqn. (6)). The main
results are given in Table 6.
(6)
(5)
The effects of the amounts of nonanenitrile (OctCN) and
KOCH3 were next studied for the TBAS-catalyzed reaction
(Table 7).
Different bases were also studied. We obtained two isomers 16
and 17 (Z + E) which differ in the relative positions of the R and
CN groups, indicative of possible migration of these two groups.
Consequently, the mechanism could be more or less similar to
We got finally satisfactory yields of condensation products
when using TBAS as PTA for 3 min under solvent-free PTC
conditions either conventional heating (D) or MW irradiation.
Table 6 Effects of the base and PTA on the reaction depicted in eqn. (4) in dry media under MW irradiation for 3 min
Yields (%)a
Base
PTA
Temperature/◦C
Conversionsa nitrile/aldehyde (%)
16 (Z + E)
17 (Z + E)
13
14
KOH
TBAB
Aliquat
TBASb
TDA-1
TBAB
TBASb
135
164
153
156
135
123
48/67
80/99
64/88
95/100
48/64
51/63
37 + 2
24 + 2
34 + 2
5 + 0
6 + 5
6 + 4
8 + 7
4 + 1
6 + 5
7 + 6
7
16
10
27
7
0
2
0
38
0
0
KOCH3
27 + 2
31 + 2
5
a Conversions and yields were evaluated by GC using an internal standard (diethyl phthalate). b Bu4N+ HSO4
.
−
Table 7 Effects of the amounts of reagents on the reaction depicted in eqn. (4) in dry media for 3 min with TBAS as the catalyst (10 mol% versus
the base) and KOCH3 as the base
Yields (%)a
OctCN (equiv.) KOCH3 (equiv.) Activation mode Temperature/◦C Conversiona nitrile/aldehyde (%)
16 (Z + E) 17 (Z + E) 14
1
1
1
1.5
2
3
MW
MW
MW
MW
MW
D
123
133
138
138
142
124
51/63
55/62
64/77
70/83
76/92
96/94
31 + 2
34 + 2
39 + 2
44 + 3
49 + 3
55 + 3
7 + 6
8 + 6
5
1
3
2
3
0
1.5
1.5
2
3
3
9 + 7
10 + 7
12 + 8
12 + 8
3
a Conversions and yields were evaluated by GC using an internal standard (diethyl phthalate).
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 5 3 4 – 1 5 4 0
1 5 3 7

View Article Online
Table 8 GC conditions and retention times (Rt) for reactants and products
Products or
reactants
Internal standard
Rt/min
GC column
GC conditions
Rt/min
1
2
DB1, 30 m, ID = 0.25 mm
100→280 ◦C (10 min), 10 ◦C min−1, PHe = 70 kPa
5.58
4.58
9.38
3Z
3E
4
16.40
15.12
22.43 + 23.24
13.34
19.04
16.26
15.50
2.87
2.32
3.15
4.99
12.84
12.35
12.47
11.74
5
6
7
8
1
12QC2/BP1, 12 m ID = 0.22 mm 100→250 ◦C (7 min), 10 ◦C min−1, PHe = 50 kPa
6.19
13
14
15
16Z
16E
17Z
17E
Yields were substantially enhanced when larger amounts of
nitrile and base were used.
by Perkin–Elmer Co. GC conditions and retention times for
reactants and products are given in Table 8.
Typical experiments
Conclusions
Phenylacetonitrile, nonanenitrile (n-octyl cyanide), phase trans-
fer agents (TBAB, Aliquat 336, 18-crown-6, TDA-1) and bases
(K2CO3, NaOH, KOH, KOCH3, K3PO4·3H2O, Cs2CO3) were
purchased from commercial sources (Acros, Aldrich or Fluka
Chemical Co.) and were used without further purification. 4-
Methoxybenzaldehyde (Acros) was distilled before use.
With phenylacetonitrile, two solvent-free methods can be used
efficiently: i) neat powdered KOH or KOCH3 at room temper-
ature with aldehyde : nitrile : base = 1 : 1 : 1 with very short
reaction times (3–10 min), and ii) with K2CO3, addition of a
phase-transfer agent and reaction for 3 min at 133 ◦C under MW
irradiation or conventional heating. By extending the reaction
time up to 10 min, five different products were obtained resulting
from phenyl or nitrile group migration. With nonanenitrile, only
the second method could be used to give access to two kinds of
condensed compounds with or without phenyl (or nitrile) group
migration.
Solvent-free uncatalyzed reaction (Tables 1, 2 and 4). Pheny-
lacetonitrile 2 (10 mmol; 1.17 g), finely ground solid KOH con-
taining 15% H2O (10 mmol; 0.65 g) and 4-methoxybenzaldehyde
1 (10 mmol; 0.68 g) were introduced successively into a Pyrex
vessel adapted to the microwave equipment and fitted with a
mechanical stirrer. MW irradiation was carried out according
to the conditions indicated in Table 2. At the end of the
reaction, organic products were extracted with ethyl acetate
and the mixture was filtered next through sintered-glass. The
products were identified (GC-MS, NMR, retention time by
comparison with authentic samples), and analyzed by GC with
an internal standard. At room temperature (Table 1), the same
Pyrex vessel was used and the mixture was mechanically stirred.
Under conventional heating conditions (Table 4), the Pyrex
vessel was introduced into a thermostatted oil bath, at the same
temperature as the final temperature under MW irradiation,
with a mechanical stirrer. The same treatment was performed in
both cases.
Generalization of these conditions to a series of aliphatic
carbonyl compounds is under progress.40
Experimental
Microwave equipment
Reactions were performed in a monomode reactor Synthewave
402 microwave device from Prolabo.21 The temperature was mea-
sured during the reaction by infrared detection, which indicates
the surface temperature after previous calibration of emissivity
in each case with an optical fibre thermometer (FTI-10 device
from Fiso). All reactions were conducted in a cylindrical Pyrex
tube under mechanical stirring to establish homogeneity in
temperature. The emitted MW power was monitored during
irradiation to maintain a constant temperature.
PTC solvent-free reaction (Tables 3–7). Phenylacetonitrile
2 (10 mmol; 1.17 g), finely ground solid KOH (10 mmol;
0.65 g), TBAB (1 mmol; 0.32 g) and 4-methoxybenzaldehyde
1 (10 mmol; 0.68 g) were introduced successively into a Pyrex
vessel adapted to the microwave equipment, fitted with a
mechanical stirrer. Treatment was exactly the same whether
the reactions were catalyzed or non-catalyzed, conducted under
MW irradiation or with conventional heating.
Characterization of products
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 chromatograph fitted with a capillary column DB5, 30 m,
1
ID = 25 lm). H and 13C NMR spectra were recorded 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.
Z-2-Phenyl-3-(4-methoxyphenyl)acrylonitrile 3Z
(RN:5432-07-5)
GC Analyses
All yields were determined by GC with diethyl phthalate as
internal standard. The GC devices (GC 9000 series, Fisons,
and GC 5160 Vega series 2, Carlo Erba) were fitted with a
non-polar capillary column, film thickness = 0.1 lm, carrier
gas = helium. GC equipment was fitted with hardware (NCI 900
series interface) and software (Turbochrom) systems developed
Purified by flash chromatography on silica gel (pentane–ether
◦
60 : 40 v/v) as white crystals. Mp 95 C (lit.41 93.5–94.5 ◦C).
1 5 3 8
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 5 3 4 – 1 5 4 0

View Article Online
MS: m/z 235 (M+, 100%), 191 (13.6), 190 (23.2), 165 (36.8), 88
(10.4). H NMR: 3.82 (s, 3H, OCH3), 6.93–6.99 (m, 2H, Hb),
E,Z-2-(4-Methoxyphenyl)-3-heptylacrylonitrile 17E + 17Z
1
7.35–7.48 (m, 3H, Hi and Hj), 7.45 (s, 1H, He), 7.63–7.69 (m,
2H, Hh), 7.86–7.91 (m, 2H, Hc). 13C NMR: 55.29 (CH3O), 108.46
(Cf), 114.26 (Cb), 118.45 (CN), 125.63 (Ch), 126.38 (Cd), 128.64
(Ci), 128.89 (Cj), 131.09 (Cc), 134.70 (Cg), 141.75 (Ce), 161.30
(Ca).
Z-2,3-Diphenylacrylonitrile 5 (RN:2510-95-4)
Purified by flash chromatography on silica gel (pentane then
pentane–ether 99 : 1 to 98 : 2 v/v) as pale yellow oil. MS (E
isomer): m/z 257 (M+, 49.6%), 172 (100), 121 (88.4), 108 (19.1),
41 (18.3). MS (Z isomer): m/z 257 (M+, 27.3%), 172 (9.7), 121
Commercial product (Lancaster Chemical Co.).
Z-2-(4-methoxyphenyl)-3-(4-methoxyphenyl)acrylonitrile 6
(RN:6443-74-9)
1
(100), 108 (33.8), 41 (13.7). H NMR (Emajor + Zminor): 0.9 (t,
3H, Hm), 1.25–1.42 (m, 8H, Hi + Hj + Hk + Hl), 1.42–1.51 (m,
2H, Hh), 2.46–2.51 (m, 2H, Hg), 3.45 (s, 3H, OCH3) (E), 3.81 (s,
3H, OCH3) (Z), 6.16–6.21 (m, 1H, Hf), 6.87–6.91 (m, 2H, Hb),
7.12–7.16 (m, 2H, Hc) (Z), 7.27–7.31 (m, 2H, Hc) (E). 13C NMR
(Emajor + Zminor): 14.09 (Cm) (E + Z), 22.54 (Cl) (E + Z), 28.21 +
28.56 + 28.75 + 29.07 + 29.43 (Ci + Cj + Ck) (E + Z), 31.52 +
31.71 (Ch) (E + Z), 36.21 + 39.54 (Cg) (E + Z), 55.23 (CH3O),
113.56 + 114.18 (Ce) (E + Z), 114.15 (Cc) (E + Z), 117.68 +
120.96 (CN) (E + Z), 126.84 + 128.73 (Cd) (E + Z), 129.79 (Cb)
(E + Z), 143.58 + 148.35 (Cf) (E + Z), 158.72 + 160.33 (Ca)
(E + Z).
Purified by flash chromatography on silica gel (pentane) as white
◦
◦
crystals. Mp 113 C (lit.38 107–107.5 C). MS: m/z 265 (M+,
100%), 250 (37.4), 191 (12.5), 190 (24.6), 178 (18.3), 152 (11.2).
1H NMR: 3.82 (s, 3H, Hl), 3.84 (s, 3H, Hk), 6.87–7.00 (2 m, 2 ×
2H, Hi + Hb), 7.33 (s, 1H, He), 7.52–7.62 (m, 2H, Hh), 7.78–7.88
(m, 2H, Hc). 13C NMR: 55.33 (Ck + Cl), 108.20 (Cf), 114.23 (Ci),
114.29 (Cb), 118.62 (CN), 126.65 + 127.24 (Cd + Cg), 126.97
(Ch), 130.81 (Cc), 139.81 (Ce), 160.01 (Cj), 161.00 (Ca).
References
1 J. C. Guillemin, C. M. Breneman, J. C. Joseph and J. P. Ferris, Chem.
Eur. J., 1998, 4, 1074–1082.
2 M. J. Fraysse, Perfum. Flavor., 1980, 4, 11–12, (Chem. Abstr., 1980,
92, 185698).
3 F. Fringuelli, G. Pani, O. Piermatti and F. Pizzo, Tetrahedron, 1994,
50, 11499–11508.
4 R. S. H. Liu, H. Matsumoto, A. E. Asato, M. Denny, Y. Shichida,
T. Yoshizawa and F. W. Dahlquist, J. Am. Chem. Soc., 1981, 103,
7195–7201.
Z-2-(4-Methoxyphenyl)-3-phenylacrylonitrile 7 (RN:5840-59-5)
5 K. Mori, “Synthetic chemistry of insect pheromones and juvenile
hormones” in: Recent Developments in the chemistry of natural carbon
compounds, Akademiai Budapest, 1979, vol. 9, p. 11.
6 J. R. Peat and B. Jeffcoat, Proc. Easter Sch. Agric. Sci. (Univ.
Nottingham), 1982, 33, 237–249, (Chem. Abstr., 1982, 98, 1617).
7 F. Michel, L. Mercklein, A. Crastes de Paulet, J. C. Dore, J. Gilbert
and J. F. Miquel, Prostaglandins, 1984, 27, 69–84.
8 S. Muruyama, X.-T. Tao, H. Hokari, T. Noh, Y. Zhang, T. Wada, H.
Sasabe, H. Suzuki, T. Watanabe and S. Miyata, Chem. Lett., 1998,
749–750.
Purified by recryst◦allization (MeOH) as yellow crystals. Mp 92–
93 ◦C (lit.19 90–91 C). MS: m/z 235 (M+, 100%), 219 (12.9), 204
(21.5), 190 (21.8), 177 (21.7), 165 (48.8). 1H NMR:19 3.81 (s, 3H,
Hk), 6.87–7.01 (m, 2H, Hi), 7.33–7.51 (m, 4H, Ha + Hb + He),
7.52–7.68 (m, 2H, Hh), 7.84–7.93 (m, 2H, Hc). 13C NMR: 55.29
(Ck), 111.09 (Cf), 114.32 (Ci), 118.05 (CN), 127.01(Cg), 127.18
(Ch), 128.76 + 128.93 (Cb + Cc), 130.01 (Ca), 133.84 (Cd), 139.96
(Ce), 160.33 (Cj).
9 (a) J. L. Segura, N. Martin and M. Hanack, Eur. J. Org. Chem., 1999,
643–651; (b) R. Gomez, J. L. Segura and N. Martin, Chem. Commun.,
1999, 619–620.
10 Meyer and Frost, Annalen, 1888, 250, 157.
11 N. P. Buu-Hoi and N. D. Xuong, Bull. Soc. Chim. Fr., 1957, 650–655.
12 F. Ladhar and R. El Gharbi, Synth. Commun., 1991, 21, 413–417.
13 C. M. L. Van de Velde, F. Blockhuys, C. Van Alsenoy, A. T. H. Lenstra
and H. J. Geise, J. Chem. Soc., Perkin Trans. 2, 2002, 1345–1351.
14 S. Wawzonek, E. M. Smolin, Org. Synth., coll. vol. III, Wiley, New
York, 1955.
Z-2-Heptyl-3-(4-methoxyphenyl)acrylonitrile 16Z
15 B. A. D’sa, P. Kisanga and J. G. Verkade, J. Org. Chem., 1988, 63,
3961–3967.
16 B. Zupancic and M. Kokalj, Synthesis, 1981, 913–915.
17 D. C. Dittmer, Chem. Ind., 1997, 779–784.
18 J. O. Metzger, Angew. Chem., Int. Ed., 1998, 37, 2975–2978.
19 D. Villemin, A. Jullien and N. Bar, Green Chem., 2003, 5, 467–469.
20 F. Toda, K. Tanaka and K. Hamai, J. Chem. Soc., Perkin Trans. 1,
1990, 3207–3209.
21 A. Loupy, A. Petit, J. Hamelin, F. Texier-Boullet, P. Jacquault and
D. Mathe´, Synthesis, 1998, 1213–1234.
22 K. Tanaka and F. Toda F., Chem. Rev., 2000, 100, 1025–1074.
23 S. Deshayes, M. Liagre, A. Loupy, J. L. Luche and A. Petit,
Tetrahedron, 1999, 55, 10851–10870.
24 A. Loupy, A. Petit and D. Bogdal, in: Microwaves in Organic
Synthesis, Wiley-VCH, Weinheim, 2002, ch. 5, 147–180.
25 G. Soula, J. Org. Chem., 1985, 50, 3717–3721.
Purified by flash chromatography on silica gel (pentane then
pentane–ether 99 : 1 to 98 : 2 v/v) as pale yellow oil. MS: m/z
257 (M+, 52.5%), 172 (100), 121 (71.2), 115 (18.0), 41 (13.7). 1H
NMR: 0.83 (t, 3H, Hm), 1.26–1.44 (m, 8H, Hi + Hj + Hk +
Hl), 1.61–1.72 (m, 2H, Hh), 2.35–2.44 (m, 2H, Hg), 3.87 (s, 3H,
OCH3), 6.78 (s, 1H, He), 6.91–6.98 (m, 2H, Hb), 7.71–7.77 (m,
2H, Hc). 13C NMR: 14.02 (Cm), 22.56 + 28.35 + 28.62 + 28.91 +
31.66 (Cg + Ch + Ci + Cj + Ck + Cl), 55.28 (CH3O), 108.52 (Cf),
114.06 (Cb), 119.34 (CN), 126.55 (Cd), 130.15 (Cc), 142.73 (Ce),
160.67 (Ca).
26 L. Perreux and A. Loupy, Tetrahedron, 2001, 57, 9199–9223.
27 L. Perreux, A. Loupy, in: Microwaves in Organic Synthesis, Wiley-
VCH, Weinheim, 2002, ch. 3, 61–114.
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 5 3 4 – 1 5 4 0
1 5 3 9

View Article Online
28 D. A. Lewis, in Microwave Processing of Materials III, R. L. Beatty,
W. H. Sutton and M. F. Iskander, eds., Mater. Res. Soc. Symp. Proc.
series, vol. 269, Materials Research Society, Warrendale, PA, 1992,
pp. 21–31.
34 J. J. Eisch, A. A. Aradi, M. A. Lucarelli and Y. Qian, Tetrahedron,
1998, 54, 1169–1184.
35 S. Thorand and N. Krause, J. Org. Chem, 1998, 63, 8551–8553.
36 G. W. Gockel, S. A. Dibiase and B. A. Lipisko, Tetrahedron Lett.,
1976, 39, 3495–3496.
37 S. A. Dibiase, B. A. Lipisko, A. Haag, R. A. Wolak and G. W. Gokel,
J. Org. Chem., 1979, 44, 4640–4648.
38 S. A. Dibiase and G. W. Gokel, Synthesis, 1977, 629–632.
39 T. Cuvigny, P. Hullot and M. Larcheveˆque, J. Organomet. Chem.,
1973, 57, C36–C38.
29 S. Chatti, M. Bortolussi and A. Loupy, Tetrahedron, 2000, 56, 5877–
5883.
30 L. Perreux and A. Loupy, Org. Prep. Proced. Int., 2003, 35, 361–368.
31 J. Cvengros, S. Toma, S. Marque and A. Loupy, Can. J. Chem., 2004,
82, 1365–1371.
32 M. Cariou and M. Lamant, C. R. Acad. Sci. Paris, Ser. IIc, 1965,
260, 4542–4544.
33 M. Cariou, Bull. Soc. Chim. Fr., 1969, 210–217.
40 A. Loupy, M. Pellet, A. Petit, R. Guillot (to be published).
41 S. S. Kulp and C. B. Caldwell, J. Org. Chem., 1980, 45, 171–173.
1 5 4 0
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 5 3 4 – 1 5 4 0