Push-pull structures with a pyrazine core and hexatriene chain: synthesis and light-emitting properties

Article abstract of DOI:10.1016/j.tet.2009.03.042

In this paper, we describe the synthesis of various push-pull molecules with a central pyrazine unit connected to a hexatriene chain terminated by various p-substituted phenyl groups. The key steps involve metallation and subsequent transmetallation of 2-

Full text of DOI:10.1016/j.tet.2009.03.042

Tetrahedron 65 (2009) 4190–4200
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Push–pull structures with a pyrazine core and hexatriene chain: synthesis
and light-emitting properties
*
´
´
´
Nordine Hebbar, Yvan Ramondenc, Gerard Ple, Georges Dupas, Nelly Ple
Laboratoire de Chimie Organique Fine et He´te´rocyclique, UMR 6014 IRCOF-INSA, Universite´ de Rouen, 76131 Mont-Saint-Aignan, Cedex, France
a r t i c l e i n f o
a b s t r a c t
Article history:
In this paper, we describe the synthesis of various push–pull molecules with a central pyrazine unit
connected to a hexatriene chain terminated by various p-substituted phenyl groups. The key steps in-
volve metallation and subsequent transmetallation of 2-chloro and 2,6-dichloropyrazine followed by
a Negishi cross-coupling reaction of the intermediate organozinc derivative with (2E,4E)-5-bromo-
pentadienal. The aldehydes are then submitted to a Wittig reaction with the appropriate phosphonium
salts readily obtained from various substituted benzyl alcohols. The light-emitting properties of the so
obtained molecules are then investigated in terms of absorption and emission spectra and non-linear
optics experiments have been carried out in two cases.
Received 22 December 2008
Received in revised form 3 March 2009
Accepted 14 March 2009
Available online 26 March 2009
Keywords:
Pyrazines
Metallation
Cross-coupling reactions
Fluorescence
Conjugation
Ó 2009 Elsevier Ltd. All rights reserved.
Non-linear optics
1. Introduction
linear optics (NLOs), harmonics generation, optical limitation,
two-photon absorption (TPA) and optical imaging of biological
In the past two decades,
p
-conjugated organic compounds have
materials. Moreover, such compounds can be used as convenient
precursors for electron-transport materials (or emitter materials) in
organic electroluminescent devices.
attracted much attention due to their potential applications in
various fields such as liquid crystals,1 components of organic light-
emitting devices (OLEDs) for display and lighting,2 field effect
transistors (FETs),3 single molecular electronics4 and non-linear
optical materials.5 The fluorescent chromophores, generally known
The introduction of a heteroaryl moiety into extended
p-sys-
tems is of interest to bring considerable effect onto optical prop-
erties such as molar extinction, band position absorption and
to have planar and rigid
p-conjugated systems, are also of interest
fluorescence spectra. The
p-deficient character of the pyrazine ring
as functional materials in the molecular probes.6 The advantages of
molecular fluorescence for sensing and switching are very impor-
tant:7 indeed they enable a high sensitivity of detection, an ‘on-off’
switchability, a subnanometer spatial resolution and a submilli-
second temporal resolution.
allows us to use it as a -electron acceptor.
p
Previously, a theoretical investigation and molecular design
of chromophores containing ethylene–pyrazine bridge and do-
nor or acceptor groups has been performed and has established
that such compounds are good candidates for NLO properties
Among them, push–pull polyenes are of particular interest,
with large molecular first hyperpolarizabilities (
liminary study urged us to synthesize new donor/acceptor
substituted pyrazines with a large -extended conjugation,
b). This pre-
generally, these compounds have a symmetrical structure (D–
p–D
or A– –A) or an asymmetrical one (D– –A), where A and D are
p
p
p
electron acceptor or donor groups. The A and D substituents are
connected with a polymethine chain (PC) containing alternating
single and double bonds playing the role of electron transmitters
for the internal charge transfer (ICT).
which could have potential interesting applications in NLO and
fluorescence.
Herein, we report the synthesis of various linear compounds
(type I) with a pyrazine moiety connected to a donor or an acceptor
group though an oligoene chain as a bridge (Scheme 1).
Asymmetrical push–pull polyenes with electron donor–accep-
tor p-conjugated system have received much attention due to their
high polarizability and thus are promising compounds for non-
D or A
Type I
Scheme 1.
N
N
Cl
* Corresponding author. Tel.: þ33 235522902; fax: þ33 235522962.
´
E-mail address: nelly.ple@insa-rouen.fr (N. Ple).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.03.042

N. Hebbar et al. / Tetrahedron 65 (2009) 4190–4200
4191
2. Results and discussion
2.1. Synthesis
group allowing a better conjugation. The stereomers (1E,3E,5Z) and
(1E,3E,5E) were purified using flash column chromatography but
not separated even by recrystallization.
This result allowed us then to carry out the Wittig reaction of
compound 2 with phosphonium salts 3a, 3e and 3f using n-butyl-
lithium as a base. The chromophores of type I were obtained in
moderate to good yields as a mixture of isomers 5Z and 5E, which
were inseparable (Scheme 5).
The synthesis of compounds of type I was initiated from com-
mercially available 2-chloropyrazine 1 using metallation and cross-
coupling reactions, according to the following general synthetic
way (Scheme 2).
N
D or A
N
ZnCl
Cl
N
N
N
N
Br
O
O
N
Cl
N
Cl
Cl
Type I
1
1a
2
Scheme 2.
N
N
ZnCl
Cl
N
3 eq.
Br
1) 1.3 eq. LTMP/THF/-78°C/30 min
2) 3 eq. ZnCl2/-78°C to r.t.
Cl
O
O
5% Pd(PPh3)4/THF/r.t./2h
72%
N
N
N
Cl
1
2
1a
Scheme 3.
The key compound of this synthesis is the aldehyde 2, readily
obtained via a Negishi coupling reaction between the (2E,4E)-5-
bromopentadienal8 and the organozinc pyrazine 1a.9a This last
intermediate results from an ortho-lithiation of the chloropyr-
azine9a followed by reaction with zinc chloride. The choice of an
organozinc intermediate, which is at once more stable and less
reactive towards electrophiles than analogous lithio derivatives,
allowed us to carry out the Negishi coupling reaction without
protection of the aldehyde group. The last step using both Wittig
and Wadsworth–Emmons reactions afforded the expected target
polyenes.
Chromophores of type I with all trans configuration and a better
extended conjugation would have higher absorption wavelengths
and extinction coefficients in UV spectra as well as better hyper-
polarizability making them more attractive. A method to transform
cis-stilbenes into trans-stilbenes has previously been described
using iodine catalyzed isomerization.11 Under these conditions, the
isomer mixtures 5a,e,f led to the corresponding (1E,3E,5E) config-
uration in quantitative yields (Scheme 6).
+
Ar
N
N
N
Ar
PPh3, Br
O
The all trans aldehyde 2 was obtained in good yield (72%) from 1
according to the experimental conditions for Negishi coupling9
(Scheme 3).
n-BuLi/THF/ 0°C to r.t. /4h
N
Cl
isomers
Cl
2
Ar
5Z : 5E
The various polyene derivatives are obtained via Wittig-type
olefination known as a powerful tool for creating carbon–carbon
bonds. Implementation of the Wittig reaction beforehand requires
the preparation of phosphonium salts 3, which were obtained in
moderate to good yields from corresponding benzyl alcohols by
reaction with commercial triphenylphosphonium bromide.10 To
evaluate the potential of a polyenal in a Wittig reaction, the phos-
phonium salts 3 were reacted with 5-bromopentadienal with
n-butyllithium or potassium tert-butoxide as bases, leading to
corresponding 6-arylbromohexatrienes 4 as a mixture of isomers
(1E,3E,5Z) and (1E,3E,5E) where the 5Z isomer was the major
product (Scheme 4). It must be noticed that compound 4b was
obtained as a sole isomer E. We have no real explanation for this
difference of stereoselectivity in the case of 4b, but it could be
noticed that this compound contains the best electron donating
5a p-OC8H17Ph 89%
65 : 35
59 : 41
66 : 34
5e p-NO2Ph
63%
5f p-NMe2Ph 70%
Scheme 5.
Ar
N
N
10% (mole) I2
CH2Cl2
Ar
N
Cl
N
Cl
Ar
isomers 5Z : 5E
5a p-OC8H17Ph 89%
65 : 35
59 : 41
66 : 34
(1E, 3E, 5E)
5a, 5e, 5f
5e p-NO2Ph
63%
5f p-NMe2Ph 70%
Scheme 6.
_
+
OH
PPh3 , Br
Br
1 eq. PPh3, HBr
O
Ar
Ar
Ar
Ar
H
H
Br
H
H
Base/THF/0°C - r.t.
Ar
isomers: 5Z : 5E
3a
3b
3c
3d
3e
3f
p OC8H17Ph
Julolidinyl
2-Thienyl
pCF3Ph
92%
93%
80%
67%
95%
100%
4a
4b
p OC8H17Ph 93%
55 : 45
Julolidinyl
92%
99%
54%
0 : 100
58 : 42
68 : 32
4c 2-Thienyl
4d
pCF3Ph
pNO2Ph
pNO2Ph
4e
67%
56 : 44
pNMe2Ph
Scheme 4.

4192
N. Hebbar et al. / Tetrahedron 65 (2009) 4190–4200
N
N
1 eq. 4b / 5% Pd(PPh3)4
N
N
ZnCl
Cl
1)1.3 eq. LTMP/THF/-78°C
N
N
THF/r.t./ 3h
2) 3 eq.ZnCl2/-78°C
50%
N
Cl
Cl
5b
1
N
CN
N
O
CH2(CN)2 /1% β-alanine
EtOH/ Δ / 5h
CN
N
Cl
2
N
Cl
5g
71%
Scheme 7.
Table 1
Selected correlations from HMBC 1H–13C spectrum of compound 7
Two other chromophores 5b and 5g were synthesized in all
trans configuration using another way. So compound 5b was
obtained in one step by a Negishi coupling reaction of the bromo
derivative 4b with chloropyrazine via the organozinc pyrazine.
Alternatively compound 5g was obtained via Knoevenagel con-
densation of malononitrile with aldehyde 2 under base catalysis
0
0
0
0
C6 ,
C2
,
C3
,
C5
,
d
¼148.1 ppm
d
¼148.8 ppm
d
¼143.3 ppm
d
¼142.9 ppm
H4,
H5,
d
d
¼7.67 ppm
¼7.36 ppm
3J
2J
d
3J
d
d
2J
d
4J
Hpyr
,
d
¼8.45 ppm 3J
d
d
involving b-alanine (Scheme 7).
To extend the conjugation along the chromophores, in order to
increase their optical properties, a second arm, constituted by aryl-
or heteroaryl group and/or polyenic chain, could be connected at
On the other hand, to confirm this result, a structure elucidation
of the deuterated compound 7 has been carried out by applying
various NMR experiments (1H, 13C, COSY, HMQC, HMBC).
the 50 position of the pyrazine ring, to afford D–
p–A–p–D struc-
The 1H and COSY H–H spectra allow determination of chemical
shifts and J-coupling constants of every hydrogen atom. The J-mod
tures. Introduction of such substituents requires the presence of
a halogen atom or a stannyl group at this position to perform cross-
coupling reactions.
Regioselective functionalization at the C5 or C6 position of
2-halogenopyrazines has been previously described using metal-
lation and subsequent reaction with electrophiles.12
13C spectrum highlights six CH (
d: 193.8, 149.8, 142.9, 135.6, 135.0,
133.7 ppm) and three quaternary carbons 148.8, 148.1,
(d:
143.3 ppm); the triplet at 143.3 ppm indicates that this carbon is
linked with the deuterium atom. The correlations observed with an
experiment HMQC 1H–13C allow the assignment of every ethylenic
The metallation was carried out with the acetal derivative 6
resulting from protection of the aldehyde group of compound 2
with triethyl orthoformate and catalytic amounts of NBS in ethanol.
Lithiation of compound 6 was achieved with 1.3 equiv of LTMP
at ꢀ78 ꢁC in THF for 15 min followed by reaction with various
electrophiles for a time t leading, after deprotection of the aldehyde
group, to the trisubstituted pyrazines 7–12 (Scheme 8, Table 1).
To determine unambiguously the position of substituents E on
the pyrazine ring, compound 11 was compared with 11b obtained
via a Negishi coupling reaction between the (2E,4E)-5-bromo-
pentadienal and the organozinc pyrazine 1b resulting from
metallation and transmetallation of the 2,6-dichloropyrazine
(Scheme 9).
0
carbon and the pyrazine carbon C5 with a chemical shift at
142.9 ppm.
0
To determine the chemical shifts of the quaternary carbons C2
and C3 an experiment HMBC 1H–13C with an evolution delay of
0
7 Hz (corresponding to two or three bond coupling) has been per-
formed. The signal at 148.1 ppm has two correlations with H4
(
d
¼7.67 ppm) and H5
(
d
¼7.36 ppm) corresponding to the coupling
3
2
0
0
0
constants: JC2 ,H4 and JC2 ,H5 can be assigned to C2 , whereas only
one correlation was determined between the signal at 148.8 ppm
and H5 (3JC3 ,H5) allowing an assignment to the carbon C3 . More-
over, on the 2D HMBC 1H–13C map three other correlation peaks
must be taken in consideration: first a weak correlation peak be-
0
0
The melting points and NMR spectra (1H, 13C) of compounds 11
and 11b are identical, allowing to assign the same structure for both
compounds, with insertion of the second chlorine atom at the C5
position.
0
tween the ethylenic H5 and the C6 of the pyrazine ring according to
4
0
0
a
JH5,C6 and two correlations between the pyrazine H5
(d
¼8.45)
0
0
and the quaternary carbons C2
¼143.3 ppm) linked to the deuterium atom (Table 1, Fig. 1).
(d
¼148.1 ppm) and C5
(d
OEt
OEt
N
N
N
O
HC(OEt)3 / 1% NBS
2
N
Cl
Cl
EtOH/ r.t. / 2h
100%
Cl
6
OEt
OEt
N
N
N
N
1) 1.3 eq. LTMP/THF/ -78 °C/ 15 min
O
2) n eq. Electrophile / THF/ -78 °C/ t
3) HCl
6
E
Cl
7
E = D
54%
8
E = p-MeOPhCH(OH) 73%
9
E = CH3CH(OH)
69%
63%
57%
60%
10 E = SnBu3
11 E = Cl
12 E = Br
Scheme 8.

N. Hebbar et al. / Tetrahedron 65 (2009) 4190–4200
4193
N
N
N
ZnCl
Cl
N
N
1.3 eq.
1) 1.3 eq. LTMP/THF/-78 °C/30 min
3 eq. ZnCl2/-78 °C to r..t
Cl
Br
O
O
Cl
5% Pd(PPh3)4/THF/r.t./2h
46%
Cl
N
Cl
Cl
11b
1b
Scheme 9.
reacted with iodine to give the 5-iodo derivative. This compound
underwenta furtherisomerizationinvolvingintermediateformation
of thediiododerivative leadingto compound13. Such isomerizations
resulting from a halogen migration have been previously reported in
pyridine, pyrimidine and pyrazine12,13 series, it is known as a ‘halo-
gen-dance’ mechanism, which implies a halogen–lithium exchange.
Two other chromophores with a bromine atom or a chloropyr-
4J (H5/C6')
3J (H6/C2')
H
H
H
O
1'
3
5
N
1
2'
4
2
6'
H
2J (H6'/C5')
H
H
5'
3'
D
N
Cl
4'
0
azine as substituent at the C5 position have been synthesized using
Figure 1.
compound 12 as starting material (Scheme 11).
This synthetic way involved first a Wittig condensation performed
with aldehyde 12 and phosphonium 3b leading to compound 14 in
good yield (89%). In a second step a Stille cross-coupling reaction of
14 with 2-chloro-6-tributylstannylpyrazine12c afforded compound
15 with a more efficient electro-attractive bispyrazine as the sub-
stituent. This enhancement of the electron-withdrawing character
would cause an important red-shift for the absorption and emis-
sion maxima.
These results allowed us to determine unambiguously the
structure of compound 7 as the (2E,4E)-5-(30-chloro-50-deutero-
pyrazin-20-yl)penta-2,4-dienal (Fig. 1).
When the metallation of 6 was carried out under previous
conditions (1.3 equiv; LTMP/ꢀ78 ꢁC/THF/15 min) followed by
reaction with iodine (1 equiv) as the electrophile, a mixture of
inseparable mono and diiodo derivatives was obtained in a 1:1
ratio determined by 1H NMR spectroscopy. Such results have
been previously reported with the 2-fluoro-3-phenylpyrazine
and it was highlighted that the ratio between monoiodo and
diiodo derivatives depended on the amounts of base and io-
dine. Use of an excess of LTMP (3.1 equiv) and 1.1 equiv of
2.2. Geometrical, electronic, spectral and NLO properties
2.2.1. Geometry
iodine led to
(Scheme 10).
a
single monoiodopyrazine 13 in 58% yield
Since a twisted structure could be induced by the steric hin-
0
drance of a chlorine atom at the C3 position, we performed quan-
OEt
N
N
OEt
O
1) 3.1 eq. LTMP/THF/-78 °C/15 min
I
2) 1.1 eq. I2/THF/-78 °C/90 min.
N
Cl
N
Cl
6
13
3) HCl
58%
Scheme 10.
As previously, various NMR experiments (1H, 13C, COSY, HMQC,
HMBC) were performed to determine unambiguously the position
of the iodine atom on the pyrazine ring. The 1H, 13C, COSY H–H
experiments afforded assignment of every hydrogen of the ali-
tum mechanical calculations of the geometry and electronic
structure using the ab-initio DFT method at the B3LYP level of
theory14 with 6-31G basis set15 for various compounds of type I
*
bearing an hydrogen or a chlorine atom at C2 position.
phatic chain and H5 or H6
(d
¼8.44 ppm) of pyrazine. The NMR 13
C
0
0
Ar
N
spin echo spectrum allowed the differentiation of the six CH and
the three quaternary carbons (
d
¼149.7, 148.1, 114.8 ppm), this latter
Type I
X = H, Cl
N
X
with the upfield chemical shift being connected to the iodine atom.
A further HMQC 1H–13C experiment allowed the assignment of the
In all cases, the geometry reveals a null dihedral angle between
the pyrazine ring and the polyenic chain. As a consequence, the
planarity of the structures could allow a high charge transfer be-
tween the electron-withdrawing pyrazine ring and the methoxy,
julolidinyl or dimethylamino donating groups involved in A–p–D
structures. This ICT could be more intensive with compound 15 and
aliphatic carbons and the pyrazine carbon (
d
¼151.3 ppm). A HMBC
1H–13C experiment was achieved with a long range delay optimized
for a coupling constant of 7 Hz to identify the two quaternary car-
0
0
bons C2 and C3 and the position of the carbon bearing the iodine
atom (Table 2 and Fig. 2).
ThecorrelatedpeaksobservedintheHMBC1H–13C spectrum of 13
0
led unequivocally to place the iodine atom at the C6 position (Fig. 2).
0
This unexpected iodination occurring at C6 whereas the other
J2 (H5 /C2')
J4 (H5/C6')
0
electrophiles take place at C5 requires some comments. It could be
assumed that lithiation led first to the 50-lithioderivative, which
J4 (H5' /C2')
H
H
O
1'
3
5
I
N
1
H
2'
4
2
J2 (H5' /C6')
Table 2
6'
Selected correlations from HMBC 1H–13C experiment spectrum of 13
H
H
3'
Cl
J3 (H5' /C3')
5'
H
N
4'
0
0
0
J3 (H5 /C3')
C2
,
d
¼149.7
C3
,
d
¼148.1
C6
4J
2J
,
d
¼114.8
H5,
d¼7.19
2J
4J
3J
3J
Hpyr
,
d
¼8.44
Figure 2.

4194
N. Hebbar et al. / Tetrahedron 65 (2009) 4190–4200
N
N
N
O
N
N
2
1) 2 eq. 3b / 2.4 eq. tBuOK/ THF/0 °C/30 min
3
Br
Cl
2) 5h/ r.t.
Br
Cl
14
91%
12
5% Pd(PPh3)4/ Toluene/Δ/ 48h
N
89%
Cl
N
SnBu3
N
N
N
3
Cl
N
N
Cl
15
Scheme 11.
All the compounds of Table 3 absorb in UV–vis (376–428 nm)
Table 3
and display visible emission (457–780 nm) with low to moderate
quantum yields.
HOMO/LUMO energy levels in pyrazine and chloropyrazine series from DFT
calculations
Comparison of spectroscopic data of compounds 5a–g high-
lights that compound 5g possessing two electron-attractor groups
(cyano groups) directly connected to the polyenic chain has the
weakest spectroscopic data. For compounds 5a, 5b and 5f with an
electron-donor group linked though a phenyl ring to the polyenic
chain, the absorption maxima are in agreement with the calculated
HOMO–LUMO gaps (Table 3 and Table 4). The julolidinyl group
known to be a better electron-donor group than dimethylamino
group or than alkoxy group gives to compound 5b the better ab-
sorption, emission maxima and quantum yield (FF¼0.20). Com-
parison of compounds 5b, 14 and 15 shows that introduction of
Ar
X¼H
X¼Cl
HOMO
(eV)
LUMO
(eV)
D
EHOMOꢀ
HOMO
(eV)
LUMO
(eV)
DEHOMOꢀ
LUMO (eV)
(eV)
LUMO
p-OMePh
p-NMe2Ph
Julolidinyl
p-NO2Ph
ꢀ5.390
ꢀ5.027
ꢀ4.796
ꢀ6.111
ꢀ2.373
ꢀ2.210
ꢀ2.112
ꢀ3.256
3.017
2.817
2.684
2.856
ꢀ5.430
ꢀ5.059
ꢀ4.830
ꢀ6.156
ꢀ2.485
ꢀ2.325
ꢀ2.231
ꢀ3.229
2.945
2.734
2.559
2.857
it would be also interesting to observe the properties of compound
5e with an A– –A structure.
p
0
a substituent at C5 position such as a bromine atom or a pyrazine
ring increases significantly the absorption and emission wave-
lengths. These results could be due to the electron-withdrawing
character of the two substituents, the pyrazine ring being more
efficient than the bromine leading to the most important modifi-
2.2.2. Electronic properties
The HOMO and LUMO levels have been calculated in pyrazine
and chloropyrazine series to appreciate the influence of the chlo-
rine atom (Table 3). While the values obtained for the analogous
compounds in each series, are similar, the presence of the chorine
atom induces a slight decrease of the HOMO–LUMO gap values
0
cations. However it could be emphasized that substitution at C5
leads also to a decrease of the quantum yield.
(D
EHOMOꢀLUMO).
2.2.3. NLO properties
Absorption and fluorescence properties. The UV–vis and fluores-
Compounds of type I, which are asymmetrical push–pull poly-
cence spectroscopic data of various oligomers performed in chloro-
form at 25 ꢁC are summarized in Table 4.
enes with electron donor–acceptor
p-conjugated system could
have a high polarizability and potential applications in quadratic
non-linear optics. The NLO measurements of the mb values of
compounds 5a and 5b were determined by using the EFISH (Elec-
tric field Induced Second Harmonic) method16 and assessed by
comparison of the DANS (dimethylaminonitrostilbene) as refer-
Table 4
Optical absorption and emission spectroscopic data for compounds 5a,b, 5e,f,g, 14
and 15 in chloroform solution (10ꢀ4 to 10ꢀ7 M) at 25 ꢁ
C
(Mꢀ1 cmꢀ1
)
lemmax (nm) FF
Stokes shift (cmꢀ1
0.17b 6280
0.20c 5783
)
a
Compound labsmax (nm)
3
ence17 (Table 5). In the scalar mb product,
dipole moment and
tensor of the molecule.
m
is the ground-state
5a
5b
5e
5f
5g
14
15
401
474
399
445
376
489
528
28,770
34,787
53,630
11,447
18,478
20,884
29,556
536
653
534
629
457
713
780
b
the vector part of the hyperpolarizability
0.43d 6336
0.07e 6574
0.03d 4720
0.09c 6425
0.02e 6120
These preliminary results indicate that compounds of type I
have appreciable non-linear properties, comparable with those of
the DANS. It can be noticed that replacement of the electron-donor
a
ꢂ10%. Quantum yields are determined by comparison with references selected
according to the excitation wavelength of the studied compound.
Table 5
b
Quantum yield of fluorescence determined using harmane in 0.1 M H2SO4 as
Longest wavelength absorption maxima lmax in CHCl3 and mb (EFISH measurement
at 1907 nm in CHCl3)
a standard (FF¼0.83), excitation at 381 nm.
c
Quantum yield of fluorescence determined using cyanine 5 in PBS as a standard
mbꢃ10ꢀ48 esu
m
(D)
(
FF¼0.20), excitation at 560 nm.
Compound
lmax (nm)
d
Quantum yield of fluorescence determined using fluorescein in 0.1 M NaOH as
DANS
5a
5b
427
401
474
350
220
1040
6.6
4.0
8.0
a standard (FF¼0.90), excitation at 422 nm.
e
Quantum yield of fluorescence determined using Rodamin 6G in water as
a standard (FF¼0.76), excitation at 500 nm.

N. Hebbar et al. / Tetrahedron 65 (2009) 4190–4200
4195
alkoxy group by julolidyl group improves significantly the qua-
dratic hyperpolarizability, which is multiplied by a factor five.
stirred for t1 min at q1. After introduction of the appropriate elec-
trophile, the mixture was stirred for t2 min at q2. Hydrolysis was
then carried out at this temperature. When the electrophile was
iodine, a solution of sodium thiosulphate was used to remove the
excess of iodine. The resulting mixture was allowed to warm to 0 ꢁC
and a saturated aqueous solution of sodium hydrogencarbonate
was added in order to obtain a slightly basic medium. THF was
partially removed and the residue extracted with dichloromethane
(4ꢃ20 mL). The collected organic layers were dried on MgSO4 and
evaporated under reduced pressure. The crude product was puri-
fied by chromatography on silica gel.
3. Conclusion
Metallation and transmetallation of the commercial chloropyr-
azine, followed by Negishi coupling reaction or Wittig condensa-
tion allowed synthesis of a series of push–pull compounds. These
compounds have a pyrazine moiety as electron-drawing group, an
all trans hexatriene chain as conjugated link substituted by an ar-
omatic bearing electron donating or withdrawing group. A com-
pound with a bispyrazine group as also been synthesized.
A study of functionalization of the aldehyde 2 via metallation
has been performed highlighting a regioselectivity at the C5 posi-
tion with various electrophiles and at C6 position with the iodine as
the electrophile. The push–pull compounds have interesting light-
emitting properties and high Stokes shifts, two of them have been
tested for their NLO properties and promising results have been
observed.
4.3.1. (2E,4E)-5-(30-chloropyrazin-20-yl)penta-2,4-dienal (2)
This compound was obtained according to the general pro-
cedure A.
LTMP was prepared from anhydrous THF (50 mL), 2,2,6,6-tet-
ramethylpiperidine (0.63 mL, 3.67 mmol, 1.4 equiv) and n-BuLi
(2.13 mL, 3.41 mmol, 1.3 equiv, 1.6 M in hexanes) cooled at
q1¼ꢀ78 ꢁC and reacted with 2-chloropyrazine (0.23 mL, 2.62 mmol,
1 equiv) in THF (10 mL) for t1¼30 min, ZnCl2 (1.070 g, 7.86 mmol,
3 equiv) in anhydrous THF (20 mL), (2E,4E)-5-bromopenta-2,4-
dienal (0.422 g, 2.62 mmol, 1 equiv) and Pd(PPh3)4 (0.151 g,
0.13 mmol, 5 mol %) in V2¼THF (20 mL) for t2¼2 h. Eluent: pentane/
ethyl acetate (70/30). Yield: 367 mg (72%) of a yellow solid. Mp
4. Experimental section
4.1. General
Melting points were determined on a Reichert-Jung microscope
apparatus. The 1H and 13C NMR spectra were recorded on a Bruker
AC 300 (300 MHz 1H, 75 MHz 13C) instrument. CDCl3 was used as
a solvent. Microanalyses were performed on a Carlo Erba CHNOS
1160 apparatus. The IR spectra were obtained as potassium bro-
mide pellets with a Perkin Elmer Paragon 500 spectrometer. Ab-
sorption bands are given in cmꢀ1. Mass spectra were recorded with
a Jeol JMS-AX500 spectrometer or an ATI Unicam Automass, under
electron impact conditions (EI) at 70 eV ionizing potential, fitted (or
not) with a GC-mass coupling.
172 ꢁC. 1H NMR (CDCl3):
d
9.63 (d, 1H, J1–2¼7.9 Hz, H1), 8.44 (d, 1H,
60
50
0
0
0
0
J6 –5 ¼2.3 Hz, H ), 8.22 (d, 1H, J5 –6 ¼2.3 Hz, H ), 7.66 (dd, 1H, J4–3
¼
11.3 Hz and J4–5¼15.1 Hz, H4), 7.34 (d,1H, J5–4¼15.1 Hz, H5), 7.30 (dd,
1H, J3–4¼11.3 Hz and J3–2¼15.4 Hz, H3), 6.35 (dd, 1H, J2–1¼7.9 Hz and
J2–3¼15.4 Hz, H2). 13C NMR (CDCl3):
d
193.7 (C1), 149.8 (C3), 148.7
0
0
0
0
(C3 ), 148.0 (C2 ), 143.6 (C5 ), 143.2 (C6 ), 135.5 (C2), 134.9 (C4), 133.7
(C5). IR: 2831, 1675, 1589, 1446, 1376, 1170, 991, 862 cmꢀ1. MS (EI)
ꢄ
ꢄ
m/z: 194–196 (Mþ , 38%, 12%), 165–167 (Mþ ꢀCHO, 100%, 40%), 81
(55%), 65 (34%). Anal. Calcd for C9H7ClN2O (194.45): C, 55.54; H,
3.60; N, 14.40. Found: C, 55.77; H, 3.68; N, 14.53.
4.2. General procedure for the metallation reaction followed
by a Negishi coupling. Procedure A
4.4. General procedure for the synthesis of 6-arylbromo-
hexatriene 4 by Wittig reaction. Procedure C
ToTHF (V mL) under an argon atmosphere and previously cooled
at ꢀ20 ꢁC were successively added a solution of n-butyllithium
(1.6 M or 2.5 M, in hexanes, concentration determined with a so-
lution of diphenylacetic acid) and 2,2,6,6-tetramethylpiperidine
(TMPH). The reaction mixture was allowed to warm at 0 ꢁC and
stirred for 30 min.
To a solution of phosphonium salt 3 (2.14 mmol, 1.2 equiv) in
THF (80 mL) at 0 ꢁC under an argon atmosphere was slowly added
n-BuLi (2.5 M in hexane, 2.14 mmol, 1.2 equiv) for 3a and 3f or
t-BuOK (3.12 mmol, 1.8 equiv) for 3b–3e in THF (30 mL). After
30 min stirring at ꢀ78 ꢁC, (2E,4E)-5-bromopentadienal (1.71 mmol,
1.0 equiv) in THF (15 mL) was slowly added. The mixture was stir-
red for 10 min at ꢀ78 ꢁC and then for 3 h at room temperature. The
reaction mixture was quenched with a 10% aqueous solution of
NaHCO3 (20 mL). The resulting solution was then extracted with
dichloromethane (3ꢃ15 mL). The combined organic extracts were
washed with saturated brine (10 mL) and dried over MgSO4. After
evaporation the crude product was further purified by silica gel
column chromatography to give a mixture of two isomers 4 (5Z,5E).
To this previously prepared solution of LTMP in THF cooled at q1
,
the appropriate pyrazine derivative dissolved in anhydrous THF
was added and the resulting mixture was allowed to react at q1 for
t1 min. A solution of zinc dichloride (previously dried under vac-
uum with a drying gun) in THF (V1 mL) was then added. The mix-
ture was allowed to warm to room temperature and a solution of
the appropriate halogeno derivative and tetrakis (triphenylphos-
phine)palladium[0] (5 mol %) in THF (V2 mL) was then added. The
reaction mixture was stirred at room temperature for t2 min. Hy-
drolysis was carried out with a 20% aqueous solution of EDTA. The
reaction mixture was then neutralized with a saturated aqueous
solution of sodium hydrogencarbonate and extracted with
dichloromethane (3ꢃ20 mL). The collected organic layers were
dried on magnesium sulfate and evaporated under reduced pres-
sure. The crude product was purified by chromatography on silica
gel.
4.4.1. 1-Bromo-6-(p-n-octyloxyphenyl)hexa-1,3,5-triene (4a)
Yield: 1.04 g (93%) as a yellow solid. Mp >230 ꢁC. IR: 3067, 3005,
2922, 2851, 1598, 1472, 1340, 1178, 995, 847 cmꢀ1. MS (CI, iso-
ꢄ
butane) m/z: 363–365 (Mþ1, 78%), 362–364 (Mþ , 93%), 283
ꢄ
(Mþ ꢀBr, 100%), 279 (23%), 219 (19%), 167 (22%), 113 (45%), 97 (14%).
Anal. Calcd for C20H27BrO (362.9): C, 66.13; H, 7.44. Found: C, 66.17;
H, 7.52.
4.4.2. (1E,3E,5E)-1-Bromo-6-(p-n-octyloxyphenyl)hexa-1,3,5-
triene
4.3. General procedure for the metallation reaction followed
by quenching with an electrophile. Procedure B
1H NMR (CDCl3):
d
7.32 (d, 2H, J¼9.0 Hz, Harom), 6.84 (d, 2H,
J¼9.0 Hz, Harom), 6.78 (dd, 1H, J2–3¼10.9 Hz and J2–1¼13.6 Hz, H2),
The solution of LTMP was prepared as above and cooled at q1
The reagent was then added in THF. The reaction mixture was
.
6.64 (dd, 1H, J5–4¼9.4 Hz and J5–6¼15.1 Hz, H5), 6.56 (d, 1H, J6–5
¼
15.1 Hz, H6), 6.38 (dd, 1H, J4–5¼9.4 Hz and J4–3¼14.7 Hz, H4), 6.31 (d,

4196
N. Hebbar et al. / Tetrahedron 65 (2009) 4190–4200
1H, J1–2¼13.6 Hz, H1), 6.18 (dd, 1H, J3–2¼10.9 Hz and J3–4¼14.7 Hz,
H3), 3.95 (t, 2H, J¼6.4 Hz), 1.77 (m, 2H), 1.47–1.28 (m, 10H), 0.88 (t,
4.4.9. (1E,3E,5E)-1-Bromo-6-(p-trifluoromethylphenyl)hexa-1,3,5-
triene
3H, J¼6.4 Hz). 13C NMR (CDCl3):
d
159.7 (Carom), 138.2 (C2), 134.7
1H NMR (CDCl3):
d
7.56 (d, 2H, J¼8.3 Hz, Harom), 7.48 (d, 2H,
(C4), 134.2 (C6), 130.0 (Carom), 129.1 (C3), 128.1 (Carom), 126.5 (C5),
115.1 (Carom), 108.4 (C1), 68.5, 32.3, 29.8, 29.7, 26.5, 23.1, 14.6.
J¼8.3 Hz, Harom), 6.72 (dd, 1H, J2–3¼10.9 Hz and J2–1¼13.6 Hz, H2),
6.66 (dd, 1H, J5–4¼9.4 Hz and J5–6¼15.1 Hz, H5), 6.61–6.49 (m, 2H,
H6, H4), 6.32 (d, 1H, J1–2¼13.6 Hz, H1), 6.20 (dd,1H, J3–2¼10.9 Hz and
4.4.3. (1E,3E,5Z)-1-Bromo-6-(p-n-octyloxyphenyl)hexa-1,3,5-
triene
J3–4¼14.7 Hz, H3). 13C NMR (CDCl3):
d
140.8 (Carom), 136.1 (C2), 133.1
(C4), 132.8 (C6), 131.3 (C3), 130.3 (C5), 129.9 (Carom), 126.8 (Carom),
1H NMR (CDCl3):
d
7.23 (d, 2H, J¼8.7 Hz, Harom), 6.82 (d, 2H,
126.0 (Carom), 122.67 (CCF3), 110.4 (C1). 19F NMR (CDCl3):
d
ꢀ62.9.
J¼8.7 Hz, Harom), 6.83 (dd,1H, J4–5¼9.4 Hz and J4–3¼15.4 Hz, H4), 6.31
(dd, 1H, J2–3¼10.9 Hz and J2–1¼13.6 Hz, H2), 6.21 (d, 1H, J6–5
¼
4.4.10. (1E,3E,5Z)-1-Bromo-6-(p-trifluoromethylphenyl)hexa-1,3,5-
triene
6.8 Hz, H6), 6.18 (d, 1H, J1–2¼13.6 Hz, H1), 6.13 (dd, 1H, J3–2¼10.9 Hz
and J3–4¼15.1 Hz, H3), 3.95 (t, 2H, J¼6.4 Hz), 1.77 (m, 2H), 1.47–1.28
1H NMR (CDCl3):
d
7.56 (d, 2H, J¼8.3 Hz, Harom), 7.48 (d, 2H,
(m,10H), 0.88 (t, 3H, J¼6.4 Hz).13C NMR (CDCl3):
d
158.8 (Carom),138.1
J¼8.3 Hz, Harom), 6.98 (dd, 1H, J4–5¼10.2 Hz and J4–3¼15.4 Hz, H4),
(C2), 131.7 (C4), 131.4 (C6), 130.6 (C5), 130.1 (Carom), 129.0 (C3), 128.1
(Carom),114.7 (Carom),109.1 (C1), 68.5, 32.2, 29.7, 29.6, 26.4, 23.0,14.5.
6.75 (dd, 1H, J5–4¼10.6 Hz and J5–6¼7.2 Hz, H5), 6.75 (dd, 1H, J2–3
¼
10.6 Hz and J2–1¼13.6 Hz, H2), 6.43 (d, 1H, J6–5¼7.2 Hz, H6), 6.34 (d,
1H, J1–2¼13.6 Hz, H1), 6.33 (dd, 1H, J3–2¼10.6 Hz and J3–4¼15.1 Hz,
4.4.4. (1E,3E,5E)-1-Bromo-6-(90-julolidinyl)hexa-1,3,5-triene (4b)
Yield: 0.52 g (92%) as a brown solid. Mp >260 ꢁC. 1H NMR
H3). 13C NMR (CDCl3): 140.8 (Carom), 137.7 (C2), 133.5 (C4), 132.6
d
(C6), 131.8 (C5), 131.3 (C3), 126.7 (Carom), 125.9 (Carom), 122.67 (CCF3),
110.4 (C1). 19F NMR (CDCl3):
ꢀ62.9.
(CDCl3):
d
6.86 (s, 2H, Harom), 6.77 (dd, 1H, J2–1¼13.6 Hz and J2–3
¼
d
11.3 Hz, H2), 6.54 (dd, 1H, J5–4¼9.8 Hz and J5–6¼15.1 Hz, H5), 6.45 (d,
1H, J6–5¼15.1 Hz, H6), 6.36 (dd, 1H, J4–3¼14.7 Hz and J4–5¼9.8 Hz,
4.4.11. 1-Bromo-6-(p-nitrophenyl)hexa-1,3,5-triene (4e)
H4), 6.23 (d, 1H, J1–2¼15.1 Hz, H1), 6.10 (dd,1H, J3–4¼14.7 Hz and J3–2
¼
Yield: 0.23 g (67%) as a yellow solid. IR: 3054, 2030, 2858, 1728,
ꢄ
11.3 Hz, H3), 3.17 (t, 4H, J¼5.7 Hz), 2.74 (t, 4H, J¼6.4 Hz), 1.96 (m,
1588, 1511, 1342, 1175, 861, 747 cmꢀ1. MS (EI) m/z: 281–279 (Mþ
,
4H). 13C NMR (CDCl3):
d
143.2 (Carom), 138.4 (C2), 135.5 (C4 or C6),
26%), 223 (26%), 207 (29%), 170 (21%), 154 (26%), 149 (81%), 125
(24%), 109 (18%), 97 (25%), 84 (100%), 66 (49%), 57 (60%). Anal. Calcd
for C12H10BrNO2 (280.12): C, 51.45; H, 3.57; N, 5.00. Found: C, 51.54;
H, 3.72; N, 5.28.
135.3 (C4 or C6), 127.1 (C3), 125.8 (2Carom), 124.7 (Carom), 123.5 (C5),
121.6 (2Carom), 106.9 (C1), 50.3, 28.0, 22.2. IR: 3056, 3014, 2930,
2838, 2789, 1611, 1588, 1351, 1310, 1205, 1179, 986 cmꢀ1. MS (EI) m/
ꢄ
z: 329–331 (Mþ , 5%), 285 (13%), 269 (16%), 222 (22%), 207 (31%),
186 (28%), 168 (13%), 144 (75%), 130 (30%), 116 (58%), 97 (48%), 89
(48%), 73 (63%), 64 (100%). Anal. Calcd for C18H20BrN (329.9): C,
65.47; H, 6.06; N, 4.24. Found: C, 65.44; H, 6.12; N, 4.28.
4.4.12. (1E,3E,5E)-1-Bromo-6-(p-nitrophenyl)hexa-1,3,5-triene
1H NMR (CDCl3):
d
8.18 (d, 2H, J¼8.7 Hz, Harom), 7.45 (d, 2H,
J¼8.7 Hz, Harom), 6.91 (dd, 1H, J2–3¼10.9 Hz and J2–1¼13.6 Hz, H2),
6.66 (dd, 1H, J5–4¼10.9 Hz and J5–6¼15.4 Hz, H5), 6.58 (dd, 1H, J4–5
¼
4.4.5. 1-Bromo-6-(20-thienyl)hexa-1,3,5-triene (4c)
9.4 Hz and J4–3¼15.4 Hz, H4), 6.50 (d, 1H, J1–2¼13.6 Hz, H1), 6.33 (d,
1H, J6–5¼15.4 Hz, H6), 6.26 (dd, 1H, J3–2¼10.2 Hz and J3–4¼15.1 Hz,
Yield: 0.297 g (99%) as a brown solid. IR: 3076, 3054, 3032, 3020,
1600,1286, 982, 852, 843, 822, 810, 700 cmꢀ1. MS (EI) m/z: 240–242
H3). 13C NMR (CDCl3): 147.1 (Carom), 143.9 (Carom), 135.7 (C2), 133.4
d
ꢄ
(Mþ , 28%), 207 (41%), 203 (36%),185 (52%),175 (74%), 139 (24%), 131
(C4 or C5 or C6), 132.6 (C4 or C5 or C6), 132.1 (C4 or C5 or C6), 129.7
(C3), 127.2 (Carom), 124.1 (Carom), 110.9 (C1).
(42%), 207 (41%),118 (100%),111 (39%),110 (66%), 91 (71%), 55 (76%).
Anal. Calcd for C10H9BrS (241.15): C, 49.79; H, 3.73; S, 13.28. Found:
C, 49.87; H, 3.81; S, 13.36.
4.4.13. (1E,3E,5Z)-1-Bromo-6-(p-nitrophenyl)hexa-1,3,5-triene
1H NMR (CDCl3):
d
8.17 (d, 2H, J¼8.7 Hz, Harom), 7.51 (d, 2H,
4.4.6. (1E,3E,5E)-1-Bromo-6-(20-thienyl)hexa-1,3,5-triene
J¼8.7 Hz, Harom), 6.91 (dd, 1H, J4–5¼9.4 Hz and J4–3¼15.4 Hz, H4),
1H NMR (CDCl3):
d
7.19 (d, 1H, J¼5.0 Hz, Harom), 6.98 (d, 1H,
6.82 (dd, 1H, J5–4¼10.9 Hz and J5–6¼6.9 Hz, H5), 6.75 (dd, 1H, J2–3
¼
J¼3.4 Hz, Harom), 6.93 (dd, 1H, J¼5.0 Hz and J¼3.4 Hz, Harom), 6.78
(m, 3H, H2, H5, H6), 6.35 (dd, 1H, J4–5¼10.7 Hz and J4–3¼15.1 Hz, H4),
10.9 Hz and J2–1¼13.6 Hz, H2), 6.47 (d, 1H, J1–2¼13.6 Hz, H1), 6.43 (d,
1H, J6–5¼6.8 Hz, H6), 6.33 (dd, 1H, J3–2¼10.9 Hz and J3–4¼15.1 Hz,
6.27 (d, 1H, J1–2¼13.6 Hz, H1), 6.18 (dd, 1H, J3–2¼10.9 Hz and J3–4
¼
H3). 13C NMR (CDCl3): 147.1 (Carom), 143.9 (Carom), 137.6 (C2), 133.2
d
14.7 Hz, H3). 13C NMR (CDCl3):
d
142.3 (Carom), 135.3 (C2), 132.5 (C4),
(C4 or C5 or C6), 133.1 (C4 or C5 or C6), 133.0 (C4 or C5 or C6), 131.7
(C3), 127.1 (Carom), 124.5 (Carom), 111.5 (C1).
130.8 (C6), 128.5 (C5 or C3), 128.1 (C3 or C5), 127.3 (Carom), 126.8
(Carom), 125.7 (Carom), 108.8 (C1).
4.5. General procedure for the synthesis of the chromophores
of type I (5) by Wittig reaction. Procedure D
4.4.7. (1E,3E,5Z)-1-Bromo-6-(20-thienyl)hexa-1,3,5-triene
1H NMR (CDCl3):
d
7.21 (d, 1H, J¼5.0 Hz, Harom), 7.01–6.97 (m,
2H, Harom), 6.83–6.73 (m, 2H, H2, H5), 6.57 (dd, 1H, J4–5¼10.2 Hz and
To a solution of phosphonium salts 3a, 3e or 3f (2.42 mmol,
1.1 equiv) in THF (80 mL) at 0 ꢁC under an argon atmosphere, was
slowly added n-BuLi (1.6 M in hexane, 2.42 mmol, 1.1 equiv). After
30 min stirring, aldehyde 2 (2.41 mmol, 1.0 equiv) in THF (15 mL)
was slowly added. The mixture was stirred for 10 min at 0 ꢁC and
4 h at room temperature. The reaction mixture was quenched with
a 10% aqueous solution of NaHCO3 (20 mL). The resulting solution
was then extracted with dichloromethane (3ꢃ15 mL). The com-
bined organic extracts were washed with saturated brine (10 mL)
and dried over MgSO4. After evaporation the crude product was
further purified by silica gel column chromatography to give
a mixture of two isomers 5 (5Z,5E). The isomerization was realized
by 10 mol % of iodine in refluxing dichloromethane or toluene
during 4 h. A solution of sodium thiosulfate was added and after
J4–3¼15.1 Hz, H4), 6.36 (d, 1H, J1–2¼13.6 Hz, H1), 6.30 (d, 1H, J6–5
¼
7.5 Hz, H6), 6.20 (dd, 1H, J3–2¼10.9 Hz and J3–4¼15.1 Hz, H3). 13C
NMR (CDCl3): d
142.9 (Carom), 137.9 (C2), 133.7 (C4), 130.0 (C6), 128.4
(C5 or C3), 128.1 (C3 or C5), 127.1 (Carom), 126.7 (Carom), 125.0 (Carom),
109.2 (C1).
4.4.8. 1-Bromo-6-(p-trifluoromethylphenyl)hexa-1,3,5-triene (4d)
Yield: 1.04 g (54%) as a yellow solid. IR: 3054, 3019, 2024, 1612,
ꢄ
1562, 1414, 1331, 1068, 991, 735 cmꢀ1. MS (EI) m/z: 303–304 (Mþ
,
64%), 267 (31%), 247 (31%), 221 (19%), 207 (33%), 200 (40%), 165
(68%), 147 (43%), 122 (42%), 109 (38%), 97 (54%), 84 (100%), 71 (83%),
55 (81%). Anal. Calcd for C13H10BrF3 (303.12): C, 51.49; H, 3.30.
Found: C, 51.56; H, 3.34.

N. Hebbar et al. / Tetrahedron 65 (2009) 4190–4200
4197
0
extraction with dichloromethane (2ꢃ15 mL) the combined organic
extracts were dried over MgSO4. After evaporation, only isomer all E
was obtained with good purity.
H5 ), 7.63 (dd, 1H, J2–3¼11.3 Hz and J2–1¼15.1 Hz, H2), 6.91 (s, 2H,
H
arom), 6.90 (d, 1H, J1–2¼15.1 Hz, H1), 6.70 (d, 1H, J6–5¼15.1 Hz,
H6), 6.69 (dd, 1H, J4–3¼14.3 Hz and J4–5¼10.6 Hz, H4), 6.59–6.46
(m, 2H, H5 and H3), 3.19 (t, 4H, J¼5.7 Hz, CH2), 2.75 (t, 4H,
0
4.5.1. (1E,3E,5E)-1-(30-Chloropyrazin-20-yl)-6-(p-n-octyloxy-
J¼6.4 Hz, CH2), 1.96 (m, 4H, CH2). 13C NMR (CDCl3):
d
150.3 (C2 ),
0
00
0
0
0
phenyl)hexa-1,3,5-triene (5a)
147.0 (C3 ), 143.6 (C6 ), 142.7 (C6 ), 140.8 (C5 or C4), 140.7 (C5 or
00
800
Yield: 0.844 g (89%) as a yellow solid. Mp 165 ꢁC. 1H NMR
C4)0,0 139.4 (C2), 137.2 (C5), 129.5 (C3), 010 26.2 (C and C10 ), 124.5
00 00
60
0
0
0
0
(CDCl3):
d
8.41 (d, 1H, J6 –5 ¼2.3 Hz, H ), 8.13 (d, 1H, J5 –6 ¼2.3 Hz,
(C900), 123.8 (C600), 122.5 (C1), 121.6 (C5 and C7 ), 50.3 (C2 ), 28.0
(C4 ), 22.2 (C3 ). IR: 3143, 3016, 2958, 2926, 2869, 1612, 1573,
1273, 1242, 1203, 1160, 1130, 1048, 1001, 963, 880, 850, 745,
0
H5 ), 7.63 (dd, 1H, J2–3¼11.3 Hz and J2–1¼15.1 Hz, H2), 7.37 (d, 2H,
J¼8.7 Hz, Harom), 6.97 (d,1H, J1–2¼15.1 Hz, H1), 6.86 (d, 2H, J¼8.7 Hz,
ꢄ
H
arom), 6.78 (d, 1H, J6–5¼15.1 Hz, H6), 6.74 (dd, 1H, J4–3¼15.1 Hz and
719 cmꢀ1. MS (EI) m/z: 363–365 (Mþ , 96%, 31%), 249 (100%), 236
J4–5¼11.3 Hz, H4), 6.65 (d, 1H, J5–4¼11.3 Hz and J5–6¼15.1 Hz, H5),
6.58 (dd, 1H, J3–4¼14.7 Hz and J3–2¼11.3 Hz, H3), 3.97 (t, 2H,
J¼6.4 Hz),1.78 (m, 2H),1.45–1.29 (m,10H), 0.89 (t0, 3H, J¼6.4 Hz). 13C
(7%), 222 (12%), 210 (8%), 186 (36%), 181 (31%), 168 (22%), 154
(8%), 137 (6%), 109 (10%), 97 (13%), 69 (14%), 57 (18%). Anal. Calcd
for C22H22ClN3 (363.45): C, 72.64; H, 6.05; N, 11.55. Found: C,
72.51; H, 5.98; N, 11.29.
0
0
NMR (CDCl3): d
159.7 (Carom),150.1 (C2 ), 147.5 (C3 ),142.7 (C6 ),141.3
0
(C5 ), 139.7 (C4), 138.9 (C2), 135.7 (C5), 131.4 (C3), 129.8 (Carom), 128.4
(Carom), 126.7 (C6), 124.0 (C1), 115.1 (Carom), 68.4, 32.2, 29.7, 29.6,
26.4, 23.0, 14.6. IR: 3075, 3020, 2936, 2923, 1591, 1386, 1240, 1173,
4.5.5. (3E,5E)-1,1-Dicyano-6-(30-chloropyrazin-20-yl)hexa-1,3,5-
triene (5g)
ꢄ
1082, 871, 641 cmꢀ1. MS (EI) m/z: 396–398 (Mþ , 21%, 6%), 375
A mixture of aldehyde 2 (200 mg, 1.03 mmol, 1.00 equiv),
(15%), 370 (20%), 350 (27%), 337 (53%), 324 (42%), 284 (37%), 281
(65%), 269 (27%), 250 (32%), 238 (56%), 226 (43%), 208 (40%), 198
(71%), 149 (70%), 132 (51%), 121 (48%), 106 (96%), 69 (97%), 57
(100%). Anal. Calcd for C24H29ClN2O (396.45): C, 33.71; H, 1.87; N,
8.74. Found: C, 33.79; H, 1.89; N, 8.73.
malononitrile (68 mg, 1.03 mmol, 1.00 equiv) and b-alanine
(0.92 mg, 0.01 mmol, 0.01 equiv) was stirred for 5 h in refluxing
ethanol (60 mL) under argon atmosphere. The ethanol was re-
moved under vacuum and water was added (20 mL). The resulting
solution was then extracted with dichloromethane (3ꢃ15 mL) and
the combined organic extracts were dried over MgSO4. After
evaporation the crude product was further purified by silica gel
column chromatography.
4.5.2. (1E,3E,5E)-1-(30-Chloropyrazin-20-yl)-6-(p-nitrophenyl)-
hexa-1,3,5-triene (5e)
Yield: 0.305 g (63%) as a yellow solid. Mp >260 ꢁC. 1H NMR
Yield: 0.177 g (71%) as a yellow solid. Mp 218 ꢁC.1H NMR (CDCl3):
60
60
50
0
0
0
0
0
0
(CDCl3):
H
d
8.45 (d, 1H, J6 –5 ¼2.3 Hz, H ), 8.20 (d, 2H, J¼9.0 Hz,
d
8.53 (d, 1H, J6 –5 ¼2.3 Hz, H ), 8.31 (d, 1H, J5 –6 ¼2.3 Hz, H ), 7.72
50
arom), 8.19 (d, 1H, J5 –6 ¼2.3 Hz, H ), 7.65 (dd, 1H, J2–3¼10.6 Hz and
(dd, 1H, J5–4¼11.3 Hz and J5–6¼14.7 Hz, H5), 7.55 (d, 1H, J2–3
¼
0
0
J2–1¼15.1 Hz, H2), 7.56 (d, 2H, J¼9.0 Hz, Harom), 7.08 (d, 1H, J1–2
¼
0
11.7 Hz, H2), 7.42 (d, 1H, J6–5¼15.1 Hz, H6), 7.15 (dd, 1H, J4–3¼14.7 Hz
and J4–5¼11.3 Hz, H4), 7.00 (dd, 1H, J3–4¼14.7 Hz and J3–2¼11.3 Hz,
14.7 Hz, H1), 7.05 (dd, 1H, J3–4¼15.1 Hz and J3–2¼11.7 Hz, H3), 6.76–
0
0
6.71 (m, 3H, H4, H5, H6). 13C NMR (CDCl3):
d
149.5 (Carom), 147.9 (C2 ),
H3). 13C NMR (CDCl3): 158.9 (C2), 147.0 (C3 ), 148.0 (C4), 147.8 (C2 ),
d
0
0
0
0
0
147.2 (C3 ), 143.7 (Carom), 142.8 (C5 ), 142.0 (C6 ), 137.8 (C4 or C2),
137.7 (C2 or C4), 135.4 (C5), 133.2 (C3 or C6), 132.8 (C6 or C3), 127.3
(Carom), 126.6 (C1), 124.5 (Carom). IR: 1600, 1584, 1513, 1446, 1379,
1345,1258,1174,1133,1080,1049,1001, 868, 831, 803, 629 cmꢀ1. MS
148.8 (C5 ), 143.2 (C6 ), 135.2 (C5 or C6), 135.1 (C6 or C5), 130.2 (C3),
113.6 (CCN), 111.6 (CCN), 85.2 (C1). IR: 3071, 3037, 3011, 2230, 1592,
1385,1341,1189,1175,1147, 859, 740, 611 cmꢀ1. MS (EI) m/z: 242–244
ꢄ
(Mþ ,100%, 34%), 207 (MꢀCl, 29%),180 (24%),165–167(55%,13%),153
ꢄ
(EI) m/z: 313–315 (Mþ , 32%, 13%), 279 (47%), 259 (12%), 256 (31%),
(2%),129 (5%),102 (27%), 76 (19%), 52 (32%). Anal. Calcd for C12H7ClN4
(242.45): C, 59.39; H, 2.89; N, 23.10. Found: C, 59.67; H, 2.92; N,
23.38.
229 (36%), 207 (34%), 185 (34%), 167 (51%), 149 (100%), 139 (20%),
129 (43%), 99 (34%), 97 (53%), 71 (64%), 57 (83%). Anal. Calcd for
C16H12ClN3O2 (313.45): C, 61.25; H, 3.83; N, 13.40. Found: C, 61.49;
H, 4.09; N, 13.63.
4.5.6. (2E,4E)-1,1-Diethoxy-5-(30-chloropyrazin-20-yl)penta-2,4-
diene (6)
4.5.3. (1E,3E,5E)-1-(30-Chloropyrazin-20-yl)-6-(p-N,N-dimethyl-
A solution of aldehyde 2 (321 mg, 1.65 mmol, 1.0 equiv), N-bro-
mosuccinimide (3.00 mg, 0.02 mmol, 0.01 equiv) and ethyl ortho-
formate (0.50 mL, 2.48 mmol, 1.5 equiv) in ethanol (40 mL) was
stirred for 2 h at room temperature. The reaction mixture was
quenched with a 10% aqueous solution of NaOH (25 mL) and the
ethanol was removed under vacuum. The resulting solution was
then extracted with dichloromethane (2ꢃ20 mL). The combined
organic extracts were washed with water (20 mL) and dried over
Na2SO4. After evaporation, the crude product was obtained in good
purity.
aminophenyl)hexa-1,3,5-triene (5f)
Yield: 0.481 g (70%) as a brown solid. Mp 207 ꢁC. 1H NMR
60
0
0
0
0
(CDCl3):
d
8.40 (d, 1H, J6 –5 ¼2.3 Hz, H ), 8.11 (d, 1H, J5 –6 ¼2.3 Hz,
0
H5 ), 7.64 (dd, 1H, J2–3¼11.3 Hz and J2–1¼15.1 Hz, H2), 7.34 (d, 2H,
J¼8.7 Hz, Harom), 6.93 (d, 1H, J1–2¼15.1 Hz, H1), 6.74 (d, 1H, J6–5
¼
15.1 Hz, H6), 6.72 (dd, 1H, J4–3¼15.1 Hz and J4–5¼11.3 Hz, H4), 6.68
(d, 2H, J¼8.7 Hz, Harom), 6.58 (dd, 1H, J5–4¼11.3 Hz and J5–6¼15.0 Hz,
H5), 6.53 (dd, 1H, J3–4¼15.1 Hz and J3–2¼11.3 Hz, H3), 2.30 (s, 6H,
00
0
0
CH3). 13C NMR (CDCl3):
d
150.8 (C1 ), 150.3 (C3 ), 147.4 (C2 ), 142.7
0
0
(C5 ), 141.0 (C6 ), 140.4 (C4), 139.2 (C2), 136.6 (C5), 130.1 (C3), 128.4
Yield:0.443 g(100%)as a brown oil.1HNMR (CDCl3):
d8.41 (d,1H,
00
00
00
60
50
(C3 ), 125.5 (C4 ), 124.7 (C6), 123.1 (C1), 112.6 (C2 ), 40.7 (CH3). IR:
3081, 3048, 3015, 2889, 2807, 1614, 1582, 1550, 1362, 1273, 1251,
J6 –5 ¼2.3 Hz, H ), 8.16 (d, 1H, J5 –6 ¼2.3 Hz, H ), 7.51 (dd, 1H, J4–3
¼
0
0
0
0
11.3 Hz and J4–5¼15.1 Hz, H4), 7.02 (d,1H, J5–4¼15.1 Hz, H5), 6.63 (dd,
1H, J3–4¼11.3 Hz and J3–2¼15.4 Hz, H3), 6.02 (dd,1H, J2–3¼15.4 Hz and
J2–1¼4.9 Hz, H2), 5.04 (d,1H, J1–2¼4.9 Hz, H1), 3.61 (m, 4H, CH2), 1.22
ꢄ
1010, 948, 884, 860, 810, 743 cmꢀ1. MS (EI) m/z: 311–313 (Mþ , 84%,
39%), 276 (MꢀCl, 5%), 231 (10%), 197 (100%), 196 (25%), 184 (16%),
165–167 (20%, 7%), 158 (22%), 134 (73%), 121 (28%). Anal. Calcd for
C18H18ClN3 (311.45): C, 69.35; H, 5.78; N, 13.48. Found: C, 69.34; H,
5.35; N, 13.28.
0
0
(t, 6H, J¼6.8 Hz, CH3).13C NMR (CDCl3):
d
149.4 (C2 ),147.7 (C3 ),142.8
0
0
(C6 ),142.1 (C5 ),137.3 (C4),136.4 (C2),132.3 (C3),126.3 (C5),100.7 (C1),
61.3 (CCH2), 15.6 (CCH3). IR: 2975, 2931, 2877, 1609, 1512, 1441, 1379,
ꢄ
1343,1132,1051, 997, 874, 739 cmꢀ1. MS (EI) m/z: 268–270 (Mþ , 36%,
4.5.4. (1E,3E,5E)-1-(30-Chloropyrazin-20-yl)-6-(900-julolidinyl)-
12%), 241 (29%), 239 (78%), 223 (100%), 209 (26%), 195 (74%), 167
(97%),152 (18%),131 (22%),103 (15%), 77 (38%), 53 (49%). Anal. Calcd
for C13H17ClN2O2 (268.45): C, 58.11; H, 6.33; N, 10.43. Found: C,
58.06; H, 5.92; N, 10.45.
hexa-1,3,5-triene (5b)
Yield: 0.285 g (50%) as a purple solid. Mp 225 ꢁC. 1H NMR
60
0
0
0
0
(CDCl3):
d
8.39 (d, 1H, J6 –5 ¼2.3 Hz, H ), 8.09 (d, 1H, J5 –6 ¼2.3 Hz,

4198
N. Hebbar et al. / Tetrahedron 65 (2009) 4190–4200
0
0
0
0
4.5.7. (2E,4E)-5-(30-Chloro-50-deuteriopyrazin-20-yl)penta-2,4-
dienal (7)
(C1), 159.1 (C5 ), 150.2 (C3), 147.3 (C3 ), 146.200(C2 ), 140.4 (C6 ), 135.2
00
(C2), 134.3 (C4), 133.8 (C5), 68.6 (C1 ), 24.1 (C2 ). IR: 3476, 1667, 2981,
This compound has been obtained according to general pro-
cedure B. LTMP was prepared from TMPH (0.18 mL, 1.04 mmol,
1.4 equiv), n-BuLi (1.6 M in hexanes, 0.61 mL, 0.97 mmol, 1.3 equiv)
in THF (40 mL), cooled at ꢀ78 ꢁC and treated with (2E,4E)-1,1-
diethoxy-5-(30-chloropyrazin-20-yl)penta-2,4-diene (6) (200 mg,
0.75 mmol, 1.0 equiv) in THF (15 mL) for t1¼15 min. The electro-
phile was EtOD (0.44 mL, 7.45 mmol, 10.0 equiv) in THF (10 mL) at
ꢀ78 ꢁC for 30 min. Hydrolysis was carried out with a 10% aqueous
solution of HCl (20 mL). Eluent for chromatography: pentane/ethyl
2838, 1677, 1617, 1550, 1341, 990, 943 cmꢀ1. MS (EI) m/z: 238–240
ꢄ
(Mþ , 42%, 13%), 301–303 (MꢀCHO, 47%, 16%), 195 (16%), 137 (100%),
109 (35%), 77 (69%). Anal. Calcd for C11H11ClN2O2 (238.67): C, 55.35;
H, 4.61; N, 11.74. Found: C, 55.32; H, 4.68; N, 11.75.
4.5.10. (2E,4E)-5-[30-Chloro-50-(tri-n-butylstannyl)pyrazin-20-
yl]penta-2,4-dienal (10)
This compound has been obtained according to general pro-
cedure B. LTMP was prepared from TMPH (0.20 mL, 1.17 mmol,
1.4 equiv), n-BuLi (1.6 M in hexanes, 0.68 mL, 1.08 mmol, 1.3 equiv)
in THF (40 mL), cooled at ꢀ78 ꢁC and treated with (2E,4E)-1,1-
diethoxy-5-(30-chloropyrazin-20-yl)penta-2,4-diene (6) (224 mg,
0.83 mmol, 1.0 equiv) in THF (15 mL) for t1¼15 min. The electro-
phile was tributyltin chloride (0.29 mL,1.08 mmol,1.3 equiv) in THF
(15 mL) at ꢀ78 ꢁC for 2 h. Hydrolysis was carried out with a 10%
aqueous solution of HCl (20 mL). Eluent for chromatography:
acetate (70/30). Yield: 0.080 g (54%) of a yellow solid. Mp 173 ꢁC. 1H
0
NMR (CDCl3):
d
9.63 (d, 1H, J1–2¼7.9 Hz, H1), 8.45 (s, 1H, H6 ), 7.67
(dd, 1H, J4–3¼11.3 Hz and J4–5¼15.1 Hz, H4), 7.36 (d, 1H, J5–4¼15.1 Hz,
H5), 7.30 (dd,1H, J3–4¼11.3 Hz and J3–2¼15.4 Hz, H3), 6.36 (dd,1H, J2–1
¼
7.9 Hz and J2–3¼15.4 Hz, H2). 13C NMR (CDCl3):
d
193.8 (C1), 149.8 (C3),
0
0
0
0
148.8 (C3 ), 148.1 (C2 ), 143.3 (C5 ), 142.9 (C6 ), 135.6 (C2), 135.0 (C4),
133.7 (C5). IR: 2832, 1675, 1622, 1423, 1334, 1305, 1262, 990 cmꢀ1
.
ꢄ
ꢄ
MS (EI) m/z: 195–197 (Mþ , 43%, 17%), 166–168 (Mþ ꢀCHO, 100%,
40%), 81 (43%), 65 (34%), 53 (32%). Anal. Calcd for C9H6DClN2O
(195.45): C, 55.26; H, 3.07; N, 14.33. Found: C, 55.29; H, 3.11; N,
14.36.
pentane/ethyl acetate (14:1). Yield: 0.253 g (63%) of a colourless oil.
0
1H NMR (CDCl3):
d
9.64 (d, 1H, J1–2¼7.9 Hz, H1), 8.41 (s, 1H, H6 ), 7.67
(dd, 1H, J4–3¼11.3 Hz and J4–5¼15.1 Hz, H4), 7.36 (d, 1H, J5–4¼15.1 Hz,
H5), 7.31 (dd,1H, J3–4¼11.3 Hz and J3–2¼15.1 Hz, H3), 6.35 (dd,1H, J2–1
¼
7.9 Hz and J2–3¼15.1 Hz, H2), 1.51 (m, 6H, CH2), 1.28 (m, 6H, CH2), 1.14
4.5.8. (2E,4E)-5-[30-Chloro-50-(p-methoxyphenylhydroxymethyl)-
pyrazin-20yl]penta-2,4-dienal (8)
(t, 6H, J¼8.1 Hz, CH2), 0.84 (t, 9H, J¼7.5 Hz, CH3). 13C NMR (CDCl3):
0
0
0
0
d
193.9 (C1), 172.0 (C5 ), 150.3 (C3), 150.1 (C3 ), 149.3 (C6 ), 145.5 (C2 ),
00
00
This compound has been obtained according to general pro-
cedure B. LTMP was prepared from TMPH (0.18 mL, 1.04 mmol,
1.4 equiv), n-BuLi (1.6 M in hexanes, 0.61 mL, 0.97 mmol, 1.3 equiv)
in THF (40 mL), cooled at ꢀ78 ꢁC and treated with (2E,4E)-1,1-
diethoxy-5-(30-chloropyrazin-20-yl)penta-2,4-diene (6) (200 mg,
0.75 mmol, 1.0 equiv) in THF (15 mL) for t1¼15 min. The electro-
phile was 4-methoxybenzaldehyde (0.13 mL, 1.05 mmol, 1.3 equiv)
in THF (10 mL) at ꢀ78 ꢁC for 90 min. Hydrolysis was carried out
with a 10% aqueous solution of HCl (20 mL). Eluent for chromato-
graphy: pentane/ethyl acetate (2:1). Yield: 0.195 g (73%) of
135.1 (C2 or C5), 135.0 (C5 or C2),133.9 (C4), 29.4 (C2 ), 27.6 (C3 ), 14.0
0
0
0
0
(C4 ), 12.8 (C1 ). IR: 2955, 2923, 2851, 1687, 1619, 1416, 1006;
ꢄ
988 cmꢀ1. MS (EI) m/z: 481–483–485–487–489 (Mþ , 8%, 16%, 21%,
10%, 3%), 423–425–427–429–431 (15%, 39%, 55%, 22%, 10%), 367–
369–371–373–374 (22%, 32%, 30%, 12%, 5%), 309–311–313–315–317
(32%, 70%, 100%, 48%, 20%), 284 (25%), 232 (12%), 177 (20%), 155
(25%),129 (72%),121 (12%),104 (14%), 77 (15%), 57 (20%). Anal. Calcd
for C21H33ClN2OSn (483.16): C, 52.16; H, 6.83; N, 5.80. Found: C,
52.31; H, 7.05; N, 6.10.
a brown solid. Mp 137 ꢁC.0 1H NMR (CDCl3):
d
9.67 (d, 1H, J1–2
¼
4.5.11. (2E,4E)-5-(30,50-Dichloropyrazin-20yl)penta-2,4-dienal (11)
This compound has been prepared according to procedures A
and B.
7.9 Hz, H1), 8.51 (s, 1H, H6 ), 7.66 (dd, 1H, J4–3¼11.7 Hz and J4–5
¼
14.7 Hz, H4), 7.41–7.29 (m, 4H, H3, H5, 2Harom), 6.89 (d, 2H,
J¼8.7 Hz, Harom), 6.39 (dd, 1H, J2–1¼7.9 Hz and J2–3¼15.1 Hz, H2),
5.82 (s, 1H, CHOH), 3.79 (s, 3H, CH3), 3.050 1 (s, 1H, OH). 13C NMR
4.5.11.1. Procedure A. LTMP was prepared from anhydrous THF
(50 mL), 2,2,6,6-tetramethylpiperidine (0.48 mL, 2.82 mmol,
1.4 equiv) and n-BuLi (1.05 mL, 2.62 mmol, 1.3 equiv, 2.5 M in hex-
anes) cooled at q1¼ꢀ78 ꢁC and reacted with 2,6-dichloropyrazine
(300 mg, 2.01 mmol, 1 equiv) in THF (15 mL) for t1¼2 h, ZnCl2
(830 mg, 6.04 mmol, 3 equiv) in anhydrous THF (20 mL), (2E,4E)-5-
bromopenta-2,4-dienal (0.324 g, 2.01 mmol, 1 equiv) and
Pd(PPh3)4 (0.116 g, 0.10 mmol, 5 mol %) in V2¼THF (20 mL) for
t2¼20 h. Eluent for chromatography: pentane/ethyl acetate (70:30).
Yield: 0.322 g (46%) as a pale yellow solid.
00
0
(CDCl3):
d
193.9 (C1)0, 160.1 (C5 ), 157.3 (C2 ), 150.1 (C3), 147.1 (C2 or
0
0
0
C5 ), 146.2 (C2 or C5 ), 141.3 (C6 ), 135.4 (C2), 134.5 (C4), 133.7 (C5),
0
00
00
00
00
135.5 (C3 ), 128.6 (C3 ), 114.7 (C4 ), 74.2 (C1 ), 55.7 (C6 ). IR: 3427,
2846, 1675, 1620, 1514, 1341, 1253, 1169, 1126, 833 cmꢀ1. MS (EI)
ꢄ
m/z: 330–332 (Mþ , 3%, 1%), 301–303 (MꢀCHO, 10%, 3%), 195 (16%),
137 (100%), 109 (35%), 77 (69%). Anal. Calcd for C17H15ClN2O3
(330.45): C, 76.92; H, 9.40; N, 8.47. Found: C, 76.96; H, 9.65; N,
8.51.
4.5.9. (2E,4E)-5-[30-Chloro-50-(100-hydroxyethyl)pyrazin-20-
yl]penta-2,4-dienal (9)
4.5.11.2. Procedure B. LTMP was prepared from TMPH (0.27 mL,
1.45 mmol, 1.2 equiv) and n-BuLi (2.5 M in hexanes, 0.58 mL,
1.45 mmol, 1.1 equiv) in THF (40 mL). LTMP was cooled at q1¼ꢀ78 ꢁC
and treated with (2E,4E)-1,1-diethoxy-5-(30-chloropyrazin-20-
yl)penta-2,4-diene (6) (353 mg, 1.45 mmol, 1.1 equiv) in THF (15 mL)
for t1¼15 min. The electrophile was hexachloroethane (933 mg,
3.96 mmol, 3.0 equiv) in THF (20 mL) at q2¼ꢀ78 ꢁC for t2¼3 h. Hy-
drolysis was carried out with a 10% aqueous solution of HCl (20 mL).
Eluent for chromatography: pentane/diethylether (70:30). Yield:
0.171 g (57%) as a yellow solid.
This compound has been obtained according to general pro-
cedure B. LTMP was prepared from TMPH (0.18 mL, 1.04 mmol,
1.4 equiv), n-BuLi (1.6 M in hexanes, 0.61 mL, 0.97 mmol, 1.3 equiv)
in THF (40 mL), cooled at ꢀ78 ꢁC and treated with (2E,4E)-1,1-
diethoxy-5-(30-chloropyrazin-20-yl)penta-2,4-diene (6) (200 mg,
0.75 mmol, 1.0 equiv) in THF (15 mL) for t1¼15 min. The electro-
phile was acetaldehyde (0.44 mL, 7.71 mmol, 10.0 equiv) in THF
(10 mL) at ꢀ78 ꢁC for 90 min. Hydrolysis was carried out with a 10%
aqueous solution of HCl (20 mL). Eluent for chromatography:
pentane/ethyl acetate (2:1). Yield: 0.126 g (69%) of a brown solid.
0 Mp171 ꢁC.1HNMR(CDCl3):
d
9.63(d,1H, J1–2¼7.9 Hz, H1), 8.43 (s,1H,
Mp 2002 ꢁC. 1H NMR (CDCl3):
d
9.63 (d, 1H, J1–2¼7.9 Hz, H1), 8.55 (s,
H6 ), 7.63 (dd, 1H, J4–3¼11.3 Hz and J4–5¼15.1 Hz, H4), 7.29 (d, 1H, J5–4
¼
1H, H6 ), 7.63 (dd, 1H, J4–3¼11.3 Hz and J4–5¼15.1 Hz, H4), 7.35 (d, 1H,
J5–4¼15.1 Hz, H5), 7.29 (dd, 1H, J3–4¼11.3 Hz and J3–2¼15.4 Hz, H3),
6.35 (dd, 1H, J2–1¼7.9 Hz and J2–3¼15.1 Hz, H2), 4.93 (m, 1H, CHOH),
15.1 Hz, H5), 7.28 (dd, 1H, J3–4¼11.3 Hz and J3–2¼15.4 Hz, H3), 6.36 (dd,
1H, J2–1¼7.9 Hz and J2–3¼15.4 Hz, H2). 13C NMR (CDCl3):
d
193.7 (C1),
0
0
0
0
0
0
149.5 (C3),146.6 (C3 or C5 ),146.5 (C5 or C3 ),146.1 (C2 ),142.9 (C6 ),135.8
(C2), 135.2 (C4), 132.5 (C5). IR: 3072, 2841, 1678, 1424, 1308, 1152, 1063,
2.82 (d 1H, OH),1.53 (d, 3H, J¼6.4 Hz, CH3). 13C NMR (CDCl3):
d 194.0

N. Hebbar et al. / Tetrahedron 65 (2009) 4190–4200
4199
ꢄ
993, 895, 789 cmꢀ1.MS(EI)m/z: 228–230–232 (Mþ , 38%, 20%, 4%),199–
MgSO4. The isomerization was realized by 10 mol % of iodide in
refluxing dichloromethane or toluene during 4 h. A solution of
sodium thiosulfate was added and after extraction with dichloro-
methane (2ꢃ15 mL) the combined organic extracts were dried over
MgSO4. Yield: 1.10 g (91%) as a purple solid. Mp 225 ꢁC (ethanol). 1H
201–203 (MꢀCHO, 100%, 69%, 15%), 149 (40%), 129 (23%), 102 (24%), 81
(38%). Anal. Calcd for C9H6Cl2N2O (228.90): C, 47.18; H, 2.62; N, 12.23.
Found: C, 47.09; H, 2.47; N, 12.02.
4.5.12. (2E,4E)-5-(50-Bromo-30-chloropyrazin-20-yl)penta-2,4-
dienal (12)
NMR (CDCl3):
d
8.45 (s, 1H, H5), 7.62 (dd, 1H, J2 –3 ¼11.3 Hz and J2 –1
¼
0
0
0
0
0
00
00
15.1 Hz, H2 ), 6.90 (s, 2H, H8 and H10 ), 6.79 (d, 1H, J1 –2
¼
0
0
0
40
15.1 Hz, H1 ), 6.70 (dd,1H, J4 –5 ¼10.6 Hz and J4 –3 ¼14.3 Hz, H ), 6.60
0
0
0
0
This compound has been obtained according to procedure B.
LTMP was prepared from TMPH (0.14 mL, 0.78 mmol, 1.2 equiv) and
n-BuLi (1.6 M in hexanes, 0.45 mL, 0.72 mmol, 1.1 equiv) in THF
(40 mL). LTMP was cooled at q1¼ꢀ78 ꢁC and treated with (2E,4E)-
1,1-diethoxy-5-(30-chloropyrazin-20-yl)penta-2,4-diene (188 mg,
0.65 mmol, 1.0 equiv) in THF (15 mL) for t1¼15 min, 1.2-dibromo-
ethane (0.17 mL, 1.96 mmol, 3 equiv) in THF (10 mL) at q2¼ꢀ78 ꢁC
for t2¼3 h. Hydrolysis was carried out with a 10% aqueous solution
of HCl (20 mL). Eluent for chromatography: pentane/diethylether
60
0
0
0
0
0
0
(d, 1H, J6 –5 ¼15.1 Hz, H ), 6.52 (dd, 1H, J5 –4 ¼10.6 Hz and J5 –6
¼
0
30
15.1 Hz, H5 ), 6.47 (dd,1H, J3 –2 ¼11.3 Hz and J3 –4 ¼14.3 Hz, H ), 3.19
0
0
0
0
200
400
00
00
00
00
(t, 4H,00J2 –3 ¼5.7 Hz, H ), 2.74 (t, 4H, J4 –3 ¼6.4 Hz, H ), 1.96 (m,
4H, H3 ). 13C N0MR (CDCl3):
d
148.7 (C3), 145.1 (C2), 145.0 (C50), 143.7
00
0
0
(C600), 141.4 (C4 ), 139.9 (C2 ), 137.6 (C5 ), 133.8 (0C0 6), 129.3 (C3 ), 1260.3
00
00
0
00
(C8 and00C10 ), 124.4 (C9 ), 123.070 (C6 ), 121.6 (C5 and C7 ), 121.3 (C1 ),
00
50.3 (C2 ), 28.0 (C4 ), 22.1 (C3 ). IR: 3043, 3019, 2936, 2839, 1609,
1573, 1516, 1488, 1313, 1267, 1205, 1135, 1057, 997, 880, 742, 722,
ꢄ
(80:20). Yield: 0.116 g (60%) as a yellow solid. Mp 197 ꢁC. 1H NMR
641 cmꢀ1. MS (EI) m/z: 441–443–445 (Mþ , 74%, 96%, 20%), 250
0
(CDCl3):
d
9.64 (d, 1H, J1–2¼7.9 Hz, H1), 8.52 (s, 1H, H6 ), 7.66 (dd, 1H,
(44%), 249 (100%), 236 (46%), 222 (5%), 191 (27%), 186 (59%), 173
(17%), 146 (24%), 107 (83%), 106 (90%), 86 (42%), 77 (26%), 72 (35%),
69 (17%), 58 (26%), 51 (16%). Anal. Calcd for C22H21BrClN3 (442.35):
C, 59.68; H, 4.75; N, 9.49. Found: C, 59.57; H, 4.72; N, 9.27.
J4–3¼11.3 Hz and J4–5¼15.1 Hz, H4), 7.30 (d, 1H, J5–4¼15.1 Hz, H5),
7.25 (dd, 1H, J3–4¼11.3 Hz and J3–2¼15.4 Hz, H3), 6.40 (dd, 1H, J2–1
¼
7.9 Hz and J2–3¼15.4 Hz, H2). 13C NMR (CDCl3): 0d 193.7 (C1), 149.5
0
0
0
(C3), 146.9 (C3 ), 146.3 (C2 ), 145.8 (C6 ), 137.7 (C5 ), 135.8 (C2), 135.3
(C4), 132.6 (C5). IR: 3067, 2839, 1674, 1619, 1521, 1420, 1307, 1257,
4.5.15. (100E,300E,500E)-6,60-Dichloro-5-[600-(9%-julolidinyl)-hexa-
100,300,500-trienyl]-2,20-bipyrazine (15)
ꢄ
994, 885, 775 cmꢀ1. MS (EI) m/z: 272–274–276 (Mþ , 20%, 45%, 5%),
243–245–247 (MꢀCHO, 75%, 70%, 36%), 167 (27%), 149 (54%), 129
(52%), 102 (32%), 81 (81%), 75 (41%), 51 (100%). Anal. Calcd for
C9H6BrClN2O (273.35): C, 39.51; H, 2.20; N, 10.24. Found: C, 39.46;
H, 2.22; N, 10.17.
A solution of (10E,30E,50E)-6-bromo-2-chloro-3-[60-(900-juloli-
dinyl)-hexa-10,30,50- trienyl]pyrazine (14) (329 mg, 0.75 mmol) and
2-chloro-6-tributylstannylpyrazine (331 mg, 0.75 mmol) in anhy-
drous toluene (100 mL) was degassed and placed under an argon
atmosphere. Tetrakis(triphenylphosphine)palladium[0] (43 mg,
5 mol %) was quickly added and the mixture was heated to reflux
for 48 h. The mixture was cooled and diluted with diethyl ether
(10 mL), filtered on a Celite pad and washed with dichloromethane.
The collected organic layers were dried on MgSO4 and evaporated
under reduced pressure. The crude product was recrystallized from
4.5.13. (2E,4E)-5-(30-Chloro-60-iodopyrazin-20-yl)penta-2,4-
dienal (13)
This compound has been obtained according to procedure B.
LTMP was prepared from TMPH (0.41 mL, 2.4 mmol, 3.2 equiv) in
THF (40 mL), n-BuLi (1.6 M in hexanes, 1.44 mL, 2.3 mmol,
3.1 equiv), cooled at q1¼ꢀ78 ꢁC and treated with (2E,4E)-1,1-
diethoxy-5-(30-chloropyrazin-20-yl)penta-2,4-diene (6) (200 mg,
0.75 mmol, 1.0 equiv) THF (15 mL) for t1¼15 min, iodine (213 mg,
0.84 mmol, 1.1 equiv) THF (20 mL) at q2¼ꢀ78 ꢁC for t2¼90 min.
Hydrolysis was carried out with a 10% aqueous solution of HCl
(20 mL). Eluent for chromatography: pentane/ethyl acetate (85:15).
ethanol. Yield: 0.315 g (89%) as a purple solid. Mp >260 ꢁC. 1H NMR
0
(CDCl3):
d
00
9.39 (s, 1H, H3), 9.32 (s, 1H, H3 ), 8.59 (s, 1H, H5), 7.75 (dd,
200
00
00
00
00
00
1H, J2 –3 ¼11.7 Hz and J2 –1 ¼15.1 Hz, H ), 6.93 (d, 1H, J1 –2
¼
00
400
15.1 Hz, H1 ), 6.70 (dd, 1H, J4 –5 ¼10.6 Hz and J4 3 ¼14.3 Hz, H ),
00
00
00 00
600
00
00
00
00
00
00
6.61 (d,1H,0J06 –5 ¼15.1 Hz, H ), 6.66 (dd,1H, J5 –4 ¼10.6 Hz and J5 –6
¼
300
15.1 Hz, H5 ), 6.55 (dd, 1H, J3 –2 ¼11.3 Hz and J3 –4 ¼14.3 Hz, H ),
00
00
00
00
Yield: 0.143 g (58%) as a brown solid. Mp 198 ꢁC. 1H NMR (CDCl3):
3.19 (t, 4H, J2%–3%¼5.7 Hz, H2%), 2.74 (t, 4H, J4%–3%¼6.4 Hz, H4%), 1.96
0
0
d
9.64 (d, 1H, J1–2¼7.9 Hz, H1), 8.44 (s, 1H, H5 ), 7.66 (dd, 1H, J4–3
¼
(m, 4H, H3%). 13C NMR (CDCl3): 0d 151.0 (C5), 148.09 (C6 or C6 ), 148.6
0
20
11.3 Hz and J4–5¼15.1 Hz, H4), 7.25 (dd, 1H, J3–4¼11.3 Hz and J3–2
¼
(C6 or C6 ), 146.1 (C6%00), 144.8 (C5 ), 143.9 (C2 or C2 ), 143.8 (C2 or C ),
0
0
0
0
0
0
15.4 Hz, H3), 7.19 (d, 1H, J5–4¼15.1 Hz, H5), 6.40 (dd, 1H, J2–1¼7.5 Hz
142.1 (C400), 141.3 (C2 ), 141.0 (C3 or C3 ), 140.9 (C3 or C3 ), 138.0 (C500),
0
00
and J2–3¼15.4 Hz, H2). 13C NMR (CDCl3):
d
193.7 (C1), 151.3 (C5 ),
129.5 (C3 ), 126.4 (C8% and C10%), 124.3 (C9%), 123.7 (C6 ), 122.2 (C1 ),
0
0
149.7 (C2 ), 149.2 (C30 ), 148.1 (C3 ), 136.2 (C2 or C4), 136.1 (C4 or C2),
121.6 (C5% and C7%), 50.3 (C2%), 28.0 (C4%), 22.1 (C3%). IR: 3048, 3009,
132.4 (C5), 114.8 (C6 ). IR: 3063, 2836, 1683, 1596, 1487, 1387, 1295,
2943, 2830, 1569, 1313, 1265, 1139, 803, 745, 695 cmꢀ1. MS (EI) m/z:
ꢄ
ꢄ
1211, 995, 584, 473 cmꢀ1. MS (EI) m/z: 320–322 (Mþ , 39%, 15%),
475–477–479 (Mþ , 60%, 41%, 6%), 408 (8%), 396 (14%), 350 (10%),
291293 (MꢀCHO, 72%, 50%), 262 (23%), 255 (19%), 223–225 (18%,
3%), 193–195 (MꢀI, 45%, 10%), 164–166 (Mꢀ(CHOþI), 29%, 8%), 149
(54%), 129 (69%), 111 (34%), 98 (46%), 86 (100%), 74 (54%), 51 (58%).
Anal. Calcd for C9H6ClIN2O (320.35): C, 33.71; H, 1.87; N, 8.74.
Found: C, 33.79; H, 1.89; N, 8.73.
319 (21%), 281 (19%), 262 (40%), 228 (24%), 207 (20%),183 (26%),162
(16%), 149 (65%), 119 (40%), 107 (76%), 83 (58%), 64 (100%), 57 (81%).
Anal. Calcd for C26H23Cl2N5 (475.90): C, 65.56; H, 4.83; N, 14.71.
Found: C, 65.61; H, 4.98; N, 14.87.
Acknowledgements
4.5.14. (10E,30E,50E)-6-Bromo-2-chloro-3-[60-(900-julolidinyl)-hexa-
10,30,50-trienyl]pyrazine (14)
We thank Dr. A. Barsella (IPCMS Strasboug) for his collaboration
and the determination of the mb values by the Electric Field Induced
Second Harmonic (EFISH) method and Dr. A. Romieu (IRCOF Rouen)
for his collaboration during fluorescence measurements.
To a solution of phosphonium salt 3b (2.88 g, 5.46 mmol,
2.0 equiv) in THF (100 mL) at 0 ꢁC under an argon atmosphere was
slowly added potassium tert-butoxide (0.735 g, 6.55 mmol,
2.4 equiv) in THF (40 mL). After 30 min stirring, aldehyde 12
(0.746 g, 2.73 mmol, 1.0 equiv) in THF (20 mL) was slowly added.
The mixture was stirred for 10 min at 0 ꢁC and 5 h at room tem-
perature. The reaction mixture was quenched with a 10% aqueous
solution of NaHCO3 (20 mL). The resulting solution was then
extracted with dichloromethane (3ꢃ15 mL). The combined organic
extracts were washed with saturated brine (10 mL) and dried over
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