A new series of rod-like conjugated molecules with a pyrazine or a bipyrazine core. Synthesis and light emitting properties

Article abstract of DOI:10.1016/j.tet.2011.01.068

In this paper, we describe the synthesis of a wide range of new rod-like conjugated molecules with a pyrazine or a bipyrazine core connected to electron acceptor (A) or donor (D) groups through π-conjugated bridges as transmitters for the internal charge

Full text of DOI:10.1016/j.tet.2011.01.068

Tetrahedron 67 (2011) 2287e2298
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A new series of rod-like conjugated molecules with a pyrazine or a bipyrazine
core. Synthesis and light emitting properties
*
ꢀ
ꢀ
ꢀ
Nordine Hebbar, Catherine Fiol-Petit, Yvan Ramondenc, Gerard Ple, Nelly Ple
ꢀ ꢀ
ꢀ
Laboratoire de Chimie Organique Fine et Heterocyclique, UMR 6014 CNRS, Universite et INSA de Rouen, 76821 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 a wide range of new rod-like conjugated molecules with
Received 16 December 2010
Received in revised form 14 January 2011
Accepted 22 January 2011
a pyrazine or a bipyrazine core connected to electron acceptor (A) or donor (D) groups through
p-
conjugated bridges as transmitters for the internal charge transfer (ICT). The key steps of the synthesis
involve metallation and subsequent transmetallation of 2-chloropyrazine derivatives followed by So-
nogashira or Negishi cross-coupling reactions. The bipyrazine core was obtained with a Stille cross-
coupling reaction between the 2-chloro-6-tributylstannylpyrazine and the 2-chloro-6-iodopyrazine.
Functionalization of the 6,60-dichloro-2,20-bipyrazine was performed by metallation, transmetallation
and cross-coupling reactions. The light emitting properties of the so obtained molecules are then in-
vestigated in terms of absorption and emission spectra.
Available online 28 January 2011
Keywords:
Pyrazine
Bipyrazine
Metallation
Cross-coupling reactions
Fluorescence
Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction
D or A
N
N
Organic materials with extended p-extended conjugation along
their backbone have received high interest owing to their appli-
cations in a wide range of electronic and optoelectronic devices.1
Among them, rod-like chromophores with a planar and rigid
Cl
Type I
p-conjugated system could be considered as molecular wires for
electron and energy transfer2 and also as materials in organic
photo- and electro-luminescent devices. Another interest of such
structures is their potential two-photon absorption (TPA) proper-
ties,3 defined by their cross sections (sTPA), which could find ap-
plications in number of new areas, including the fluorescence
imaging of biological samples,4 optical limiting,5 photodynamic
therapy,6 the three-dimensional optical data storage7 and micro-
fabrication.8 The most extensively investigated structural motifs
are donor-bridge-acceptor. The structureeproperty correlations of
such chromophores reveal that the cross section sTPA increases
with the donor/acceptor strength, conjugation length and planarity
We describe herein the synthesis of various new conjugated
compounds with a pyrazine or a bipyrazine core connected to
electron acceptor (A) or donor (D) groups through
p-conjugated
bridges as transmitters for the internal charge transfer (ICT)
(Scheme 1). These compounds with such a scaffold belong to di-
polar structures with De
systems (type III) and to quadrupolar structures with De
system (type IV) where A is a
or bipyrazine) (Scheme 1).
p
-A systems (type II) or De
p
-Ae
-Ae
-deficient heterocycle unit (pyrazine
p
-A
p
p-D
p
Compounds of type III with a De
p-Ae
p-A system could be
compared to compounds of type I or II (De
p-A), allowing to ap-
of the
Previously, we have reported the synthesis of various linear
dipolar De -A or quadripolar Ae -A compounds with a pyrazine
p
-centre.2b,c
preciate for compounds of type III the structureeproperties re-
lationships due to the presence of a second arm at the C6 position
on the pyrazine ring as well as the nature of the
p-conjugated
p
p
linkers (alkene or alkyne units or polyenic chain). Chromophores of
type IV have a centrosymmetric structure with a bipyrazine core
moiety connected to a donor or and acceptor group through an
oligoene chain as a bridge (type I).9
and a De
known to exhibit better two-photon activity (TPA) than the Ae
De -A systems.
p-Aep-D system, this kind of compounds is generally
p
-
ꢀ
* Corresponding author. E-mail address: nelly.ple@insa-rouen.fr (N. Ple).
p
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.01.068

2288
N. Hebbar et al. / Tetrahedron 67 (2011) 2287e2298
N
N
have been tested; the last one has given the better yield and is
reported herein.
In a first time it was necessary to synthesize the julolidinyla-
cetylene 5. This compound was obtained in two steps from the
formyljulolidine 3 as starting material, which was prepared by
Vilsmeier reaction of julolidine11 (Scheme 3).
N
N
Type II B
D
Cl
Type II A
Type III A
Cl
D
A
N
N
A
N
N
Type III B
D
Cl
Cl
D
A
N
Type III C
D
N
Cl
Cl
Cl
N
N
N
N
Scheme 3.
D
Type IV
Scheme 1.
D
The formyljulolidine 3 was reacted with 1.6 equiv of chlor-
omethyltriphenylphosphonium chloride according to the Wittig
reaction conditions and with 1.5 equiv of n-butyllithium as base,
leading to the 1-chloro-2-julolidinylethylenes 4a and 4b as a mix-
ture of isomers Z and E (35:65) with a very good yield (99%). Further
dehydrohalogenation carried out with n-butyllithium in THF at low
temperature gave quantitatively the expected compound 5.
The pyrazine derivative 1 was synthesized through the organo
2. Results and discussion
2.1. Synthesis
It is well-known that amino groups are efficient electron-do-
nating groups to induce large Stokes shifts in De -A systems be-
p
zinc intermediate 5a, obtained by deprotonation of
5 with
cause of internal charge transfer (ICT) states. Replacing dialkyl
amino groups by a cyclic tetrahydroquinoline group would be one
way to shift the absorption and emission to longer wavelengths.10
For this reason we chose to introduce the julolidinyl group be-
cause of its high electron-releasing effect.
A preliminary synthetic way has been tested to introduce
a julolidinylethynyl or a julolidinylvinyl group at the C6 position of
the 2-chloropyrazine (Scheme 2).
n-butyllithium followed by reaction with zinc chloride. The Negishi
coupling reaction of 5a with 2-chloro-6-iodopyrazine afforded 1 in
71% yield (Scheme 4).
Various attempts have been performed to synthesize compound
2, the vinylene analogous of 1. The Stille coupling reactions with
stannylpyrazine and 1-chloro-2-julolidinylethylene have failed as
well as catalytic reduction of 1 with the Lindlar catalyst. Another
way has been tested using the hydrozirconation reaction with the
Schwartz’s reagent. The acetylenic compound 1 was reacted with
1.1 equiv of Cp2ZrHCl in THF at room temperature, then a trans-
metallation of zirconium by zinc was performed by the action of
zinc chloride and the Negishi reaction was carried out with
2-chloro-6-iodopyrazine. Under these conditions, the vinylene
compound 2 was obtained in low yield (10%) besides the acetylenic
compound 1 as major product (16%) (Scheme 5).
N
N
N
N
Cl
Cl
N
2
1
N
In order to appreciate the influence on the optical properties of
the length and of the nature of the conjugated chain at the C6 and
C3 positions of pyrazine ring, we have synthesized three other
Scheme 2.
compounds of type IIIA or IIIB with a Dep-Aep-A system. These
The 2-chloro-6-julolidinylethynylpyrazine 1 could be obtained
either by a Sonogashira cross-coupling reaction between the julo-
lidinylacetylene and the 2-chloro-6-iodopyrazine or by a Neghishi
cross-coupling reaction with the organic zinc of the julolidinyla-
cetylene and the 2-chloro-6-iodopyrazine. The two synthetic ways
compounds were obtained from compounds 1 and 2 using metal-
lation at the C3 position, induced by the chlorine atom as ortho-
directing group, followed by transmetallation and cross-coupling
reactions (Scheme 6).
N
H
ZnCl
N
Cl
c
a,b
N
71%
N
N
5
1
5a
a) 1.2 eq. n-BuLi/THF/-78 °C/30 min
b) 3 eq. ZnCl2/THF/-78 °C to r.t.
c) 1 eq. 2-chloro-6-iodopyrazine/ Pd(PPh3)4/ 5% mol/THF/r.t./4 h
Scheme 4.

N. Hebbar et al. / Tetrahedron 67 (2011) 2287e2298
2289
The regioselective functionalization at the C5 or C6 position of 2-
halogenopyrazines, using this methodology, has been previously
described.13 More recently, the metallation of an acetal derivative,
the (2E,4E)-1,1-diethoxy-5-(30-chloropyrazin-20-yl)penta-2,4-diene
10 has been reported.9 Lithiation of 10, achieved with 1.3 equiv of
LTMP at low temperature and followed by reaction with various
electrophiles, has highlighted a complete functionalization of the
C6 position. This regioselectivity has been used to introduce a con-
jugated bridge at this position, using successively metallation,
transmetallation and cross-coupling reactions carried in one step
(Scheme 8).
The aldehydes 11 were obtained via a Negishi coupling reaction
between the organo zinc 10a and 1-bromo-6-aryl-hexatrienes as
a mixture of isomers (1E,3E,5Z) and (1E,3E,5E).10 The choice of an
organo zinc intermediate has been established because of a better
stability than the analogous lithio derivative and of its ability to
generate cross-coupling reaction. This latter intermediate results
from the regioselective metallation of 10 followed by reaction with
zinc chloride. It must be noticed that the yield of compounds 11
depending on the amount of metallating agent, a wide excess of
LTMP (4 equiv) was necessary to obtain the compounds 11a and 11b
in appreciable yields.
H
Cl
N
N
a, b, c
10%
N
5
N
2
a) 1.1 eq Cp2ZrHCl/THF/ r.t./30 min.
b) 3 eq. ZnCl2/THF/r.t./1 h
c) 1 eq. 2-chloro-6-iodopyrazine/ Pd(PPh3)4 5% mol/THF/ r.t./ 5 h
Scheme 5.
Metallation of 1 was performed with LTMP at the C3 position,
a further transmetallation with ZnCl2 gave the organo zinc in-
termediate 1a, which reacted with bromopolyenes 6a or 6b lead-
ing, respectively, to compounds 7 and 8. For this latter compound 8
an isomerization in all trans configuration was obtained by reaction
with iodine at reflux of CH2Cl2.9,12
The vinyl analogous of compound 8 was obtained in similar
conditions leading to compound 9 in 83% yield (Scheme 7).
With the aim to induce an expansion of the conjugation along
the chromophores and in order to improve their optical properties,
we envisaged to connect a second arm, constituted by an aryl group
and a polyenic chain, at the C6 position of the pyrazine ring of
A further Knoevenagel condensation was performed with pyr-
azinylpentadienals 11 and malonitrile under base catalysis in-
volving
b-alanine leading to trisubstituted pyrazines 12 in good
yields (Scheme 9).
During the condensation reaction of the malonitrile with 11b,
used in mixture of isomers Z/E, a total isomerization in all trans
configuration has been observed leading to compound 12b. The
same configuration all trans was also obtained for 12a.
Another chromophore of type III was obtained through a Wittig
condensation of the pyrazinylpentadienal 11b with a phosphonium
salt and butyllithium as base, leading to 13a obtained as a mixture
of isomers E/Z. To access to an all trans configuration, which induces
a better extended conjugation, an isomerization of chromophore
structures of type I affording Dep-Aep-D or Dep-Aep-A systems.
Introduction of such substituents requires the presence of a halo-
gen atom or a stannyl group at the C6 position of pyrazine ring to
perform further cross-coupling reactions. The metallation reaction
could be the strategic pathway to access to such C6 substituted
pyrazines.
Scheme 6.

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N. Hebbar et al. / Tetrahedron 67 (2011) 2287e2298
Scheme 7.
O
OEt
OEt
OEt
N
N
N
b
a
H
N
N
2
OEt
Ar
N
Cl
2
ClZn
Cl
Cl
10a
10
Ar
isomers : 5Z : 5E
a) i) 4.1 eq. LTMP/THF/-78 °C/2h ii) 3 eq. ZnCl2/-78 °C to r.t.
Br
11a
11b
Julolidinyl
p-OC8H17Ph
51% 0 : 100
51% 25 : 75
b) 3 eq.
/ Pd(PPh3)4 5% mol/THF/r.t./4 h to 18h/ HCl 10%
Ar
Scheme 8.
O
CH2(CN)2/ 1% β-alanine
N
N
CN
N
N
2
H
2
EtOH / Δ / 20h
Ar
Cl
CN
2
Ar
Cl
2
12a Ar = Julolidinyl
81%
11a, 11b
12b Ar = p-C8H17OPh 79%
Scheme 9.
13a with iodine has been performed leading to 13 in quantitative
yield (Scheme 10).
The last series of centrosymmetric chromophores (type IV) be-
long to Dep-Aep-D system with a bipyrazine core, which could be
The metallation of the two rings occurred at the C5 position in
para of the CeC linkage, the use of tributyltin chloride as electro-
phile afforded compound 16, which could undergo a further Stille
coupling reaction.
compared to a bipyridine scaffold, able to induce metal complex-
ation. To access to such structures, an efficient synthetic way could
be the functionalization of the bipyrazine core by metallation and
subsequent cross-coupling reactions. The 6,60-dichloro-2,20-bipyr-
azine 14 has been chosen as starting material, presence of a chlo-
rine atom on each ring allowing to induce an ortho-lithiation of the
neighbouring position. Then a further cross-coupling reaction
could be performed to obtain the expected structures.
The bipyrazine 14 was synthesized in very good yield with
a Stille cross-coupling reaction between the 2-chloro-6-tributyl-
stannylpyrazine and the 2-chloro-6-iodopyrazine (Scheme 11).
Lithiation of compound 14 was achieved with 2.3 equiv of LTMP
at ꢀ100 ꢁC in THF with a short time of reaction (5 min) followed by
reaction with various electrophiles for a given time t leading to the
bipyrazine derivatives 15e17 (Scheme 12).
Afirst compoundof typeV 18 has been synthesized by two different
ways either by a Stille coupling of 16 with 5-bromopentadienal in 37%
or by a Negishi reaction of the organo zinc intermediate, resulting of
reaction of the dilithio derivative with zinc chloride, which was reacted
with 5-bromopentadienal with a better yield (64%) (Scheme 13).
This last synthetic way afforded a compound of type IV with 14
as starting material. The synthesis involved metallation, trans-
metallation and a Negishi cross-coupling reactions with the
1-bromo-6-julolidinylhexatriene and was achieved in one step,
leading to the expected compound 19 in 57% yield (Scheme 14).
A Wittig reaction carried out with the dialdehyde 18 and an
appropriate phosphonium salt using n-butyllithium as a base
afforded a new chromophore of type IV obtained as a mixture of
isomers 5Z and 5E. Further iodine catalyzed isomerization led to
compound 20 in a 74% yield (Scheme 15).

N. Hebbar et al. / Tetrahedron 67 (2011) 2287e2298
2291
CF3
_
+
N
N
O
PPh3 , Br
p-CF3Ph
2
N
N
H
H
2
Cl
2
H
13a
Cl
2
n-BuLi/THF/ 0°C to r.t./ 5h
C8H17O
47%
11b
C8H17O
10%(mole) I2
CH2Cl2
100%
CF3
N
2
N
Cl
2
13
C8H17O
Scheme 10.
2.2. Geometrical and spectral properties
2.2.1. Geometry and electronic properties. Geometry of various
conjugated compounds with Ae -D, De -Ae -A and De -Ae -D
p
p
p
p
p
Scheme 11.
systems including a pyrazine or a bipyrazine core has been estab-
lished using quantum mechanical calculations by DFT methods at
the B3LYP level of theory with the 6-31G
15 set basis. In all cases, the
*
results of the calculations reveal that all molecules adopt an almost
rigid planar structure. As a consequence, for compounds 18e20 in-
cluding a bipyrazine core, the zero dihedral angle determined be-
tween the two 6-chloropyrazine rings induces a total coplanarity of
the central scaffold. For compound 19, a dihedral angle of 1.9ꢁ is
determined between the pyrazine and phenyl ring of terminal
julolidinyl group, such a geometry allowing a high charge transfer
Scheme 12.
O
N
N
N
N
a, b, c
64%
2
2
N
N
N
N
Cl
O
Cl
Cl
Cl
18
14
a) 2.3 eq; LTMP / THF / -100 °C / 5 min
b) 4 eq. ZnCl2 / THF / -100°C to r.t.
Br
O
c) 2eq.
/ Pd(PPh 3)4/THF/ r.t./5h
Scheme 13.
N
N
N
N
N
a, b, c
57%
3
3
N
N
N
N
N
Cl
Cl
Cl
Cl
19
14
a) 2.3 eq; LTMP / THF / -100°C / 5 min
b) 4 eq. ZnCl2 / THF / -100°C to r.t.
c) 2eq. 1-bromo-6-julolidinylhexatriene/ Pd(PPh3)4 5% mol/THF/ r.t./5 h
Scheme 14.
ꢁ
Thesetwolattersynthesesconstitutetwodifferentroutestoaccess
to rod-like compounds belong to De -Ae -D system with a central
core constituted by a bipyrazine unit A highly -deficient, linked to
electron-releasing groups D with a triene chain of all trans configu-
ration to assure a better internal charge transfer by conjugation.
along this elongated molecule (23.4 A between the two final
nitrogen of the julolidinyl groups) (Fig. 1). It should be noted that
such a planar structure has been previously described with
conjugated 3,30-bispyridazine molecules,14 highlighting that bipyr-
idazine and bipyrazine cores are more than planar than their
p
p
p

2292
N. Hebbar et al. / Tetrahedron 67 (2011) 2287e2298
O
N
N
OC8H17
N
N
a, b
3
3
2
C8H17O
N
N
2
N
74%
N
Cl
Cl
Cl
O
Cl
18
+
20
-
Ar
PPh3, Br
a)
/n-BuLi/THF/0°C to r.t./5 h
b)10% (mole) I2/ CH2Cl2
Scheme 15.
Fig. 1. Optimized B3LYP/6-31G geometry for 19, the printed values correspond to dihedral angles and length of the molecule.
*
3,30-bipyridine analogous, for which a twisted conformation, with
a 34.6ꢁ dihedral angle between the pyridine rings, is given in the
ground state.
The frontier molecular orbitals calculated by the DFT method for
compound 8 (Aep-D) and compound 19 (Dep-Aep-D), which bear
the most efficient donating group (i.e., julolidinyl group) are dis-
played in Fig. 2. As expected for a typical pushepull system, the
HOMOs and LUMOs exhibit a specific pattern. The HOMO is mainly
localized on the julolidinyl donating group, whereas a reverse
pattern is observed for the LUMO, which is mostly localized on the
electron-withdrawing part of the molecule (i.e., pyrazine
substituted with a dicyanohexatrienyl group) for 8 and the bipyr-
azine core for 19.
Solvent polarity induces a significant variation of the emission
wavelengths, whereas only a slight change is observed in absorp-
tion; a positive solvatochromic shift (i.e., bathochromic shift with
increasing polarity) is observed with compounds 1, 7, 11b, 12a and
20 (Dl¼53e92 nm). This means, for these compounds, that the
dipole moment of the molecule is higher in the excited state than in
the ground state, indicating the aptitude of transfer charge at the
excited state. On the contrary an important negative sol-
vatochromic shift (Dl¼132e142 nm) is observed for compounds 8
and 9 with a dicyanovinylene terminal group and with the cen-
trosymmetric compound 19.
Comparison of spectroscopic data in CH2Cl2 of compounds 1 and
2 (type II) reveals that the nature of the spacer between the julo-
Fig. 2. HOMO and LUMO molecular orbitals for compounds 8 and 19.
2.2.2. Absorption and fluorescence properties. The UVevis and
fluorescence spectroscopic data of some of the synthesized com-
pounds performed in dichloromethane and toluene at 25 ꢁC are
summarized in Table 1. These results could appreciate the influence
of the nature of the linkers between the pyrazine or bipyrazine core
and those of the substituents together with their electron donor or
acceptor character.
lidinyl group and the pyrazine ring has some influence: as already
known replacement of a triple bond by a double one induces
a significant red shift (23 nm), a similar behaviour is observed with
compounds 8 and 9. The data of compounds 7 and 8 highlight that
compound 8 possessing two electron-attractor groups (cyano
groups) directly connected to the polyenic chain has a red shift
compared with the values of compound 7.
All chromophores show an intense absorption band in the near
UVevis region however, it should be noted that for all these com-
pounds the quantum yields are generally low as well in dichloro-
methane as in a less polar solvent such as toluene, only a slight
enhancement of the quantum yield is observed in low-polarity
toluene with an exceptional high quantum yield for 1 in toluene.
Comparison of data of compounds 11 and 12 highlights that
compounds 11a and 12a substituted with a julolidinyl group,
known to be a better electron-donor group than alkoxy group, have
a higher red shift than 11b and 12b.
The compounds 8, 9 and 12a belong to type III with a pyrazine
core substituted at the C2 position by a 1,1-dicyanohexatrienyl

N. Hebbar et al. / Tetrahedron 67 (2011) 2287e2298
2293
Table 1
Optical absorption and emission spectroscopic data for compounds 1, 2, 7e9, 11a,b, 12a,b, 13, 18e20
Solvent
Toluene (
3
¼2.38)
3max (Mꢀ1 cmꢀ1
Dichloromethane (
3
¼8.93)
3max (Mꢀ1 cmꢀ1
)
lem nm
fF
Stokes
a
a
Compound
labs nm
)
lem nm
fF
Stokes
labs nm
(%)
(%)
shift (cmꢀ1
)
shift (cmꢀ1
)
1
2
7
8
415
d
27,317
d
501b
d
40
d
6
4136
d
415
438
384
396
549
400
596
530
470
436
590
327
503
347
465
403
425
508
583
27,652
30,456
39,898
37,066
33,369
32,845
46,208
17,260
54,952
11,549
8639
25,790
43,210
27,310
47,209
46,346
38,390
88,075
10,584
593b
582
0.6
3
0.5
7233
5649
10,913
7928
7363
8660
384
396
549
403
586
d
33,262
7830
8662
19,204
32,739
d
589b
9064
11,344
4306
11,373
661b
573c
719c
<0.1
<0.1
9
744c
2
612c
<0.1
11a
11b
12a
d
d
6
0.4
d
661
652
662b
0.20
3
0.2
3739
5902
7830
470
438
613
d
51,371
8872
9991
d
568
609b
3640
6410
12b
13
d
d
d
d
0.7
d
d
0.0
0.0
0.3
0.1
d
d
d
d
d
d
d
d
d
18
d
d
537a
659b
6192
4907
4510
19
481
511
583
340
494
21,602
20,739
10,584
3958
707
5425
20
567
2
2606
336
490
16,113
39,911
630b
5
4329
10,456
a
lexc¼360 nm.
b
lexc¼450 nm.
c
lexc¼488 nm.
group and at the C5 position by the julolidinyl group connected
through a double, triple or an hexatriene linker. For these com-
pounds, two absorption bands are observed, one between 396 and
436 nm and the other between 549 and 593 nm.
Absorption 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.
In order to evaluate the influence of the bipyrazine core, a more
efficient electron-withdrawing group than pyrazine, the spectro-
scopic data of the symmetrical chromophores of type IV 18e20 are
reported. For these compounds, which are prone to be planar, an
important red shift is observed for absorption and emission max-
ima with moderate to low quantum yields.
4.2. General procedure for the metallation reaction followed
by a Negishi coupling: procedure A
To THF (V mL) under an argon atmosphere and previously
cooled at ꢀ20 ꢁC were successively added a solution of n-butyl-
lithium (1.6 M or 2.5 M, in hexanes, concentration determined with
a solution 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.
3. Conclusion
Metallation and transmetallation of 2-chloropyrazine de-
rivatives and bischloropyrazine, followed by Negishi coupling re-
action and Wittig condensation allowed synthesis of a wide range
of new rod-like conjugated molecules. These compounds have
a pyrazine or a bipyrazine core moiety as electron-drawing group,
with two arms constituted by all trans hexatriene chain as conju-
gated link substituted by an aromatic bearing electron donating or
withdrawing group. The light emitting properties of the so
obtained molecules are then investigated in terms of absorption
and emission spectra to evaluate the influence of the nature of the
core and those of the length and the nature of the conjugated chain
with the terminated groups. Incorporation of a double bond or of
a hexatriene chain as linker and a bipyrazine as an electron-with-
drawing central core increases the spectroscopic data.
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 mixturewas allowed to react at q1 for t1 min.
A solution of zinc dichloride (previously dried under vacuum with
a drying gun) in THF (V1 mL) was then added. The mixture was
allowed to warm to room temperature and a solution of the ap-
propriate halogeno derivative and tetrakis (triphenylphosphine)
palladium[0] (5 mol %) in THF (V2 mL) was then added. The reaction
mixture was stirred at room temperature for t2 min. Hydrolysis 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
(3ꢂ20 mL). The collected organic layers were dried over magnesium
sulfate and evaporated under reduced pressure. The crude product
was purified by chromatography on silica gel.
4. Experimental section
4.1. General
4.3. General procedure for the metallation reaction followed
by quenching with an electrophile: procedure B
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 PerkineElmer Paragon 500 spectrometer.
The solution of LTMP was prepared as above and cooled at q1
.
The reagent was then added in THF. The reaction mixture was
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

2294
N. Hebbar et al. / Tetrahedron 67 (2011) 2287e2298
iodine, a solution of sodium thiosulfate 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
(4ꢂ20 mL). The collected organic layers were dried over MgSO4 and
evaporated under reduced pressure. The crude product was puri-
fied by chromatography on silica gel.
was then added. The mixture was allowed to warm to room tem-
perature and a solution of 2-chloro-6-iodopyrazine (2.08 mmol,
1.0 equiv) and tetrakis (triphenylphosphine)palladium[0] (5 mol %)
in THF (20 mL) was then added. The reaction mixture was stirred at
room temperature for 4 h. The reaction mixture was quenched with
a 20% aqueous solution of EDTA (20 mL). The resulting solution was
neutralized with saturated aqueous solution of sodium hydro-
gencarbonate and extracted with dichloromethane (3ꢂ20 mL). The
combined organic extracts were dried over MgSO4. After evapora-
tion the crude product was further purified by silica gel column
chromatography (pentane/ether: 80/20). Yield: 1.39 g (71%) as an
orange solid. Mp¼224 ꢁC. IR: 3037, 2935, 2840, 2612, 2360, 2183,
1600, 1545, 1379, 1312, 1241, 1208, 1184, 1150, 888, 865, 737,
695 cmꢀ1. MS (EI) m/z: 309e311 (Mþ_, 100%, 34%), 197 (16%), 149
(40%), 105 (43%), 86 (17%), 84 (34%), 77 (27%), 71 (19%), 51 (16%).
Anal. Calcd for C18H16N3Cl (309.45): C 69.80, H 5.17, N 13.57; found:
C 69.83, H 5.24, N 13.51.
4.3.1. 1-Chloro-2-(90-julolidinyl)-ethylene (4). To
a solution of
chloromethyltriphenylphosphonium chloride (3.98 mmol, 1.6 equiv)
in THF (90 mL) at 0 ꢁC under an argon atmosphere, was slowly
added n-BuLi (1.5 M in hexane, 3.74 mmol, 1.5 equiv). After 30 min
stirring at ꢀ78 ꢁC, 9-formyljulolidine (2.49 mmol, 1.0 equiv) in THF
(20 mL) was slowly added. The reaction mixture was stirred for
10 min at ꢀ78 ꢁC and then for 14 h at room temperature. The re-
action mixture was quenched with a 10% aqueous solution of
NaHCO3 (20 mL). The resulting solution was then extracted with
dichloromethane (3ꢂ15 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 (pentane/ether: 15/1) to give a mixture of
two isomers 4a/4b (65/35). Yield: 0.574 g (99%) as a yellow oil. IR:
3073, 3005, 2937, 2885, 1604, 1505, 1464, 1282, 1073, 1053, 974, 737,
685, 620 cmꢀ1. MS (EI) m/z: 233e235 (Mþ_, 100%, 34%), 204 (17%),
196 (25%), 168 (24%), 154 (14%), 141 (11%), 115 (13%), 77 (4%). Anal.
Calcd for C14H16ClN (233.45): C 71.96, H 6.85, N 6.00; found: C 71.81,
H 6.91, N 5.98.
1H NMR (CDCl3):
d
8.51 (s, 1H, H5), 8.36 (s, 1H, H3), 7.04 (s, 2H,
H
arom), 3.22 (t, 4H, J¼5.6 Hz), 2.71 (t, 4H, J¼6.4 Hz), 1.94 (m, 4H). 13
C
NMR (CDCl3): d
148.8 (C2), 144.9 (C5), 144.5 (Carom), 141.3 (C3), 140.8
(C6), 131.5 (2Carom), 121.2 (2Carom), 105.9 (Carom), 98.9 (Cc^c), 84.0
(Cc^c), 50.2 (Cjulo), 27.8 (Cjulo), 21.8 (Cjulo).
4.3.6. (E)-2-Chloro-6-[200-(90-julolidinyl)-ethylenyl]pyrazine (2). To
a solution of Cp2ZrHCl (3.10 mmol, 1.1 equiv) in THF (40 mL) at
20 ꢁC under an argon atmosphere was slowly added a solution of
compound 5 (2.82 mmol, 1.0 equiv) in THF (10 mL). The reaction
mixture was stirred for 0.5 h at 20 ꢁC. A solution of zinc dichloride
(8.47 mmol, 3.0 equiv) previously dried under vacuum with a dry-
ing gun in THF (20 mL) was then added. The reaction mixture was
4.3.2. (1E)-1-Chloro-2-(90-julolidinyl)-ethylene (4a). 1H NMR (CDCl3):
d
6.63 (s, 2H, Harom), 6.52 (d, 1H, J1e2¼13.7 Hz, H1), 6.24 (d, 1H,
stirred for 1 h and a solution of 2-chloro-6-iodopyrazine
20
J2e1¼13.6 Hz, H2), 3.05 (t, 4H, J2 e3 ¼5.6 Hz, H ), 2.63 (t, 4H,
(2.82 mmol, 1.0 equiv) and tetrakis (triphenylphosphine)palladium
[0] (5 mol %) in THF (20 mL) was then added. The reaction mixture
was stirred at room temperature for 5 h. The reaction mixture was
quenched with a 20% aqueous solution of EDTA (20 mL). The
resulting solution was neutralized with saturated aqueous solution
of sodium hydrogencarbonate and extracted with dichloromethane
(3ꢂ20 mL). The combined organic extracts were dried over MgSO4.
After evaporation the crude product was further purified by silica
gel column chromatography (pentane/ether: 80/20).
0
0
0
40
30
J4 e3 ¼6.4 Hz, H ), 1.85 (m, 4H, H ). 13C NMR (CDCl3):
d
143.2 (C6 ),
0
0
0
0
0
0
0
133.6 (C1), 125.2 (C8 þC100 ), 122.4 (C9 ), 121.6 (C5 þC7 ), 113.4 (C2), 50.2
0
0
(C2 ), 27.9 (C4 ), 22.2 (C3 ).
4.3.3. (1Z)-1-Chloro-2-(90-julolidinyl)-ethylene (4b). 1H NMR (CDCl3):
d
7.09 (s, 2H, Harom), 6.28 (d, 1H, J2e1¼7.9 Hz, H2), 5.85 (d, 1H,
0
J1e2¼7.9 Hz, H1), 3.03 (t, 4H, J2 e3 ¼5.6 Hz, H2 ), 2.63 (t, 4H,
0
0
0
40
30
J4 e3 ¼6.4 Hz, H ), 1.84 (m, 4H, H ). 13C NMR (CDCl3):
d
143.0 (C6 ),
0
0
0
0
0
0
0
129.4 (C2), 128.5 (C8 and C10 ), 121.7 (C9 ), 121.0 (C5 and C7 ), 112.5 (C1),
Yield: 0.091 g (10%) as an orange solid. Mp¼208 ꢁC. IR: 3071,
3035, 2952, 2928, 2840, 1598, 1396, 1315, 1252, 1202, 1135, 1048,
892, 877, 743, 693, 543 cmꢀ1. MS (EI) m/z: 311e313 (Mþ_, 100%,
37%), 279 (9%), 247 (6%), 218 (6%), 201 (6%), 183 (8%), 167 (16%), 149
(27%), 95 (11%), 85 (9%), 71 (15%), 57 (22%). Anal. Calcd for:
C18H18N3Cl (311.45): C 69.35, H 5.78, N 13.48; found: C 69.59, H 5.51,
N 13.32.
0
0
0
50.2 (C2 ), 28.0 (C4 ), 22.2 (C3 ).
4.3.4. Julolidinylacetylene (5). To
a solution of compound 4
(2.49 mmol, 1.0 equiv) in THF (40 mL) at ꢀ78 ꢁC under an argon
atmosphere, was slowly added n-BuLi (2.5 M in hexane, 4.98 mmol,
2.0 equiv). The reaction mixture was stirred for 2 h at ꢀ78 ꢁC. The
reaction mixture was quenched with water (20 mL). The resulting
solution was then extracted with dichloromethane (3ꢂ20 mL). The
combined organic extracts were dried over MgSO4. After evapora-
tion the crude product was obtained. Yield: 0.489 g (100%) as
a brown solid. Mp¼80 ꢁC. IR: 3273, 2927, 2839, 2092, 1604, 1502,
1074, 892 cmꢀ1. MS (EI) m/z: 197 (Mþ_, 100%), 196 (53%), 198 (14%),
1H NMR (CDCl3):
d
8.40 (s, 1H, H5), 8.25 (s, 1H, H3), 7.62 (d, 1H,
J¼16.2 Hz), 7.05 (s, 2H, Harom), 6.79 (d, 1H, J¼15.8 Hz), 3.22 (t, 4H,
J¼5.6 Hz), 2.76 (t, 4H, J¼6.4 Hz), 1.97 (m, 4H). 13C NMR (CDCl3):
d
152.9 (C6), 149.0 (C2), 144.4 (Carom), 140.8 (C5), 140.7 (C3), 137.9
(CC]C), 127.1 (2Carom), 122.9 (Carom), 121.4 (2Carom), 116.6 (CC]C),
50.2 (Cjulo), 28.1 (Cjulo), 22.0 (Cjulo).
168 (13%), 115 (10%), 166 (7%), 139 (7%). Anal. Calcd for C14H15
(197.28): C 33.71, H 1.87, N 8.74; found: C 33.79, H 1.89, N 8.73.
N
4.3.7. (3E,5E)-6-Bromo-1,1-dicyanohexa-1,3,5-triene (6b). A mix-
ture of 5-bromopenta-2,4-dienal (200 mg, 1.24 mmol, 1.00 equiv),
1H NMR (CDCl3):
d
6.92 (s, 2H, Harom), 3.16 (t, 4H, J2 e3 ¼5.6 Hz,
0
0
0
40
30
0
H2 ), 2.19 (s, 1H, H1), 2.69 (t, 4H, J4 e3 ¼6.4 Hz, H ), 1.93 (m, 4H, H ).
malononitrile (82 mg, 1.24 mmol, 1.00 equiv) and
b-alanine
0
0
0
0
0
0
13C NMR (CDCl3):
d
143.32 (C6 ), 131.0 (C8 þC10 ), 121.2 (C50 þC7 ),
(1.10 mg, 0.012 mmol, 0.01 equiv) was stirred at 20 ꢁC for 2 h in
ethanol (60 L) under an argon atmosphere. The ethanol was re-
moved under vacuum and water was added (20 mL). The resulting
solution was then extracted with dichloromethane (3ꢂ15 mL) and
the combined organic extracts were dried over MgSO4. After
evaporation the crude was further purified by silica gel column
chromatography (CH2Cl2). Yield: 0.197 g (76%) as a brown solid.
Mp¼211 ꢁC. IR: 3083, 3038, 2924, 2846, 2286, 2228, 1593, 1353,
1327, 1262, 987, 875, 801, 729, 690, 610 cmꢀ1. MS (EI) m/z: 208e210
0
0
0
107.7 (C9 ), 85.6 (C2), 74.4 (C1), 50.2 (C2 ), 27.9 (C4 ), 22.2 (C3 ).
4.3.5. 2-Chloro-6-[200-(90-julolidinyl)ethynyl]pyrazine (1). To a solu-
tion of compound 5 (2.08 mmol, 1.0 equiv) in THF (40 mL) at ꢀ78 ꢁC
under an argon atmosphere, was slowly added n-BuLi (2.5 M in
hexane, 2.29 mmol, 1.1 equiv). The reaction mixture was stirred for
0.5 h at ꢀ78 ꢁC. A solution of zinc dichloride (4.16 mmol, 2.0 equiv)
previously dried under vacuum with a drying gun in THF (20 mL)

N. Hebbar et al. / Tetrahedron 67 (2011) 2287e2298
2295
(Mþ_, 73%), 179 (42%), 175 (40%), 164 (53%), 151 (41%), 141 (53%), 130
(79%), 114 (84%), 109 (75%), 97 (70%), 91 (59%), 83 (73%), 73 (100%),
60 (63%), 57 (91%). Anal. Calcd for C8H5N2Br (208.9): C 45.96, H 2.39,
N 13.40; found: C 46.15, H 2.44, N 13.56.
J6e5¼14.7 Hz, H6),.7.16 (dd, 1H, J4e3¼14.7 and J4e5¼11.3 Hz, H4), 7.06
(s, 2H, Harom), 6.96 (dd, 1H, J3e4¼14.7 and J3e2¼11.3 Hz, H3), 3.25 (t,
4H, J¼5.6 Hz), 2.72 (t, 4H, J¼6.4 Hz), 1.95 (m, 4H). 13C NMR (CDCl3):
0
0
d
158.9 (C2), 148.6 (C4), 147.9 (C3 ), 145.3 (C6 ), 145.0 (Carom), 143.5
0 0
1H NMR (CDCl3):
d
7.56 (d, 1H, J2e3¼11.7 Hz, H2), 7.26 (dd, 1H,
(C2 ), 140.1 (C5 ), 135.6 (C6), 134.1 (C5), 131.9 (Carom), 129.6 (C3), 121.3
(Carom), 113.8 (CCN), 111.8 (CCN), 105.7 (Carom), 102.1 (Cc^c), 86.0
(Cc^c), 84.3 (C1), 50.2 (Cjulo), 27.9 (Cjulo), 21.7 (Cjulo).
J4e3¼15.1 and J4e5¼11.3 Hz, H4), 6.90 (dd, 1H, J3e4¼15.1 and
J3e2¼11.7 Hz, H3), 6.80 (dd,1H, J5e4¼11.3 and J5e6¼14.3 Hz, H5), 6.70
(d, 1H, J6e5¼14.3 Hz, H6). 13C NMR (CDCl3):
d
159.4 (C2), 144.3 (C4),
131.4 (C3), 129.0 (C5), 121.4 (C6), 113.5 (CCN), 111.6 (CCN), 85.3 (C1).
4.3.10. (3E,5E)-1,1-Dicyano-6-[30-chloro-50-[(E)-2000-(900-julolidinyl)-
ethylenyl]pyrazin-20-yl]-hexa-1,3,5-triene (9). This compound was
obtained according to the general procedure A.
4.3.8. (10E,30E,50E)-2-chloro-6-[2000-(900-julolidinyl)ethynyl]-3-[60-(p-
trifluoromethylphenyl)-hexa-10,30,50-trienyl]pyrazine (7). This com-
pound was obtained according to the general procedure A.
LTMP was prepared from anhydrous THF (50 mL), 2,2,6,6-tet-
ramethylpiperidine (0.27 mL, 1.58 mmol, 1,4 equiv) and n-BuLi
(0.77 mL, 1.47 mmol, 1.3 equiv, 1.9 M in hexanes) cooled at
q1¼ꢀ78 ꢁC and reacted with 1 (1.13 mmol, 1 equiv) in THF (20 mL)
for t1¼30 min, ZnCl2 (0.463 g, 3.40 mmol, 3 equiv) in anhydrous
THF (20 mL), 1-bromo-6-p-trifluoromethylphenylhexa-1,3,5-triene
(0.203 g, 0.97 mmol, 1 equiv) and Pd(PPh3)4 (0.065 g, 0.06 mmol,
5 mol %) in V2¼THF (20 mL) for t2¼5 h. The crude product was
recrystallized from ethanol. 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 extraction
with dichloromethane (2ꢂ15 mL) the combined organic extracts
were dried over MgSO4. After evaporation, only isomer all E was
obtained with good purity. Yield: 0.439 g (73%) as a purple solid.
Mp>260 ꢁC. IR: 3026, 2941, 2841, 2186, 1596, 1517, 1444, 1322, 1273,
1164, 1122, 1066, 1002, 890, 866, 809 cmꢀ1. MS (EI) m/z: 531e533
(Mþ_, 43%, 16%), 505 (14%), 491 (22%), 447 (36%), 358 (25%), 346
(17%), 315 (19%), 281 (36%), 231 (49%), 213 (40%), 178 (41%), 152
(53%), 126 (87%), 117 (55%), 93 (75%), 57 (100%). Anal. Calcd for
C31H25N3ClF3 (531.45): C 70.00, H 4.70, N 7.90; found: C 70.16, H
4.87, N 7.96.
LTMP was prepared from anhydrous THF (50 mL), 2,2,6,6-tet-
ramethylpiperidine (0.17 mL, 0.98 mmol, 1.4 equiv) and n-BuLi
(0.47 mL, 0.91 mmol, 1.3 equiv, 1.9 M in hexanes) cooled at
q1¼ꢀ78 ꢁC and reacted with 2 (0.70 mmol, 1 equiv) in THF (15 mL)
for t1¼30 min, ZnCl2 (0.287 g, 2.10 mmol, 3 equiv) in anhydrous
THF (15 mL), 6-bromo-1,1-dicyanohexa-1,3,5-triene 6b (0.146 g,
0.70 mmol, 1 equiv) and Pd(PPh3)4 (0.040 g, 0.04 mmol, 5 mol %) in
V2¼THF (20 mL) for t2¼4 h. The crude product was recrystallized
from ethanol. Yield: 0.254 g (83%) as a blue solid. Mp>260 ꢁC. IR:
3026, 2948, 2841, 2226, 2183, 1593, 1530, 1461, 1310, 1248, 1180,
1143,1063, 998, 960, 943, 887, 834, 750 cmꢀ1. MS (EI) m/z: 439e441
(Mþ_, 33%, 10%), 412 (10%), 320 (9%), 264 (8%), 236 (15%), 207 (29%),
196 (13%), 153 (31%), 149 (99%), 121 (34%), 95 (37%), 84 (100%), 55
(47%). Anal. Calcd for C26H22N5Cl (439.45): C 71.00, H 5.01, N 15.93;
found: C 71.07, H 5.12, N 16.02.
0
1H NMR (CDCl3):
d
8.40 (s, 1H, H6 ), 7.67 (d, 1H, J¼15.4 Hz), 7.62
(dd, 1H, J5e4¼11.3 and J5e6¼14.7 Hz, H5), 7.52 (d, 1H, J2e3¼11.7, H2),
7.39 (d, 1H, J6e5¼14.7 Hz, H6), 7.16 (dd, 1H, J4e3¼14.7 and
J4e5¼11.3 Hz, H4), 7.08 (s, 2H, Harom), 6.93 (dd, 1H, J3e4¼14.7 and
J3e2¼11.3 Hz, H3), 6.81 (d, 1H, J¼15.4 Hz), 3.25 (t, 4H, J¼5.6 Hz), 2.76
(t, 4H, J¼6.4 Hz), 1.97 (m, 4H). 13C NMR (CDCl3):
d
159.2 (C2), 1520.8
0
0
0
(C5 ), 149.2 (C4), 148.6 (C3 ), 145.1 (Carom), 142.8 (C2 ), 141.7 (C6 ),
139.5 (Cc]c), 136.6 (C6), 132.4 (C5), 128.9 (C3), 127.7 (Carom), 122.9
(Carom), 121.5 (Carom), 116.5 (Cc]c), 114.0 (CCN), 112.0 (CCN), 83.4 (C1),
50.3 (Cjulo), 28.1 (Cjulo), 21.9 (Cjulo).
1H NMR (CDCl3):
d
8.46 (s, 1H, H5), 7.58 (d, 2H, J¼8.7 Hz, Harom),
20
0
0
0
0
7.47 (dd,1H, J2 e3 ¼10.2 and J2 e1 ¼15.1 Hz, H ), 7.42 (d, 2H, J¼8.7 Hz,
10
H
arom), 7.09 (d, 1H, J1 e2 ¼15.1 Hz, H ), 7.05 (s, 2H, Harom), 7.04e6.90
0
0
0
0
0
0
(m, 2H, H4 and H5 ), 6.73e6.66 (m, 2H, H3 and H6 ), 3.25 (t, 4H,
J¼5.6 Hz), 2.75 (t, 4H, J¼6.4 Hz), 1.95 (m, 4H). 13C NMR (CDCl3):
4.3.11. (2E,4E)-5-[30-Chloro-50-[(100E,300E,500E)-600-(9000-julolidinyl)-
hexa-100,300,500-trienyl]pyrazin-20-yl]penta-2,4-dienal (11a). This com-
pound was obtained according to the general procedure A.
d
150.0 (C3), 146.8 (Carom), 146.2 (C2), 0143.7 (C5), 140.8 (Carom), 140.7
0 0 0 0
(C6 ), 137.4 (C4 ), 137.1 (C2 ), 134.3 (C5 ), 133.3 (C3 ), 131.3 (C6), 128.7
(Carom), 126.9 (Carom), 126.3 (Carom), 126.1 (C10), 125.9 (Carom), 123.0
(CF3), 120.2 (Carom), 105.8 (Carom), 101.7 (Cc^c), 85.0 (Cc^c), 50.2
LTMP was prepared from anhydrous THF (80 mL), 2,2,6,6-tet-
ramethylpiperidine (0.80 mL, 4.70 mmol, 4.2 equiv) and n-BuLi
(1.84 mL, 4.59 mmol, 4.1 equiv, 2.5 M in hexanes) cooled at
q1¼ꢀ78 ꢁC and reacted with 10 (1.12 mmol, 1 equiv) in THF (20 mL)
for t1¼15 min, ZnCl2 (0.630 g, 4.59 mmol, 4.1 equiv) in anhydrous
THF (20 mL), 1-bromo-6-(90-julolidinyl)hexa-1,3,5-triene (0.370 g,
1.12 mmol, 1 equiv) and Pd(PPh3)4 (0.065 g, 0.06 mmol, 5 mol %) in
V2¼THF (20 mL) for t2¼18 h. Hydrolysis was carried out with a 10%
aqueous solution of HCl (20 mL). The crude product was recrys-
tallized from ethanol. Yield: 0.199 g (51%) as a purple solid.
Mp>260 ꢁC. IR: 2939, 2845, 2360, 2337, 1680, 1668, 1574, 1447,
1313, 1206, 1156, 1123, 993, 909 cmꢀ1. MS (EI) m/z: 443e445 (Mþ_,
25%, 9%), 404 (17%), 362 (26%), 333 (54%), 316 (40%), 278 (40%), 244
(50%), 220 (18%), 208 (21%), 186 (21%), 147 (28%), 127 (45%), 91
(100%), 60 (70%). Anal. Calcd for C27H26N3OCl (443.45): C 73.06, H
(Cjulo), 27.9 (Cjulo), 21.7 (Cjulo). 19F NMR (CDCl3):
d
ꢀ62.9.
4.3.9. (3E,5E)-1,1-Dicyano-6-[30-chloro-50-(julolidinylethynyl)pyr-
azin-20-yl]-hexa-1,3,5-triene (8). This compound was obtained
according to the general procedure A.
LTMP was prepared from anhydrous THF (50 mL), 2,2,6,6-tet-
ramethylpiperidine (0.23 mL, 1.40 mmol, 1.4 equiv) and n-BuLi
(0.65 mL, 1.26 mmol, 1.3 equiv, 1.9 M in hexanes) cooled at
q1¼ꢀ78 ꢁC and reacted with 1 (0.97 mmol, 1 equiv) in THF (15 mL)
for t1¼30 min, ZnCl2 (0.397 g, 2.91 mmol, 3 equiv) in anhydrous
THF (15 mL), 6-bromo-1,1-dicyanohexa-1,3,5-triene
6 (0.203 g,
0.97 mmol, 1 equiv) and Pd(PPh3)4 (0.056 g, 0.05 mmol, 5 mol %) in
V2¼THF (20 mL) for t2¼4 h. The crude product was recrystallized
from ethanol. Yield: 0.326 g (77%) as a purple solid. Mp>260 ꢁC. IR:
3031, 2934, 2835, 2219, 2179, 1601, 1528, 1312, 1240, 1159, 910, 888,
741, 697 cmꢀ1. MS (EI) m/z: 437e439 (Mþ_, 15%, 6%), 418 (10%), 392
(44%), 378 (14%), 366 (9%), 349 (46%), 319 (20%), 285 (51%), 264
(28%), 240 (15%), 218 (26%), 208 (30%), 176 (32%), 166 (100%), 148
(62%), 122 (65%), 99 (89%), 84 (100%), 55 (98%). Anal. Calcd for
C26H20N5Cl (437.45): C 71.32, H 4.57, N 16.00; found: C 72.34, H 4.61,
5.86, N 9.47; found: C 73.14, H 5.93, N 9.56.
0
1H NMR (CDCl3):
d
9.68 (d, 1H, J1e2¼7.9 Hz, H1), 8.36 (s, 1H, H6 ),
7.63 (dd, 1H, J4e3¼11.3 and J4e5¼14.7 Hz, H4), 7.53 (dd, 1H,
200
J2 e3 ¼11.3 and J2 e1 ¼15.1 Hz, H ), 7.40 (d, 1H, J5e4¼14.7 Hz, H5),
7.36 (dd, 1H, J3e4¼11.3 and J3e2¼15.1 Hz, H3), 6.91 (s, 2H, Harom),
00
00
00
00
00
00
600
6.79e6.67 (m, 2H, H4 and H5 ), 6.61 (d, 1H, J6 5 ¼010 5.1 Hz, H ), 6.55
00 00
(dd, 1H, J3 e4 ¼14.7 and J3 e2 ¼11.3 Hz, H3 ), 6.48 (d, 1H,
00
00
00
00
100
J1 e2 ¼14.7 Hz, H ), 6.40 (dd, 1H, J2e1¼7.9 and J2e3¼15.1 Hz, H2),
00
00
N 16.10.
3.19 (t, 4H, J¼5.6 Hz), 2.74 (t, 4H, J¼6.4 Hz), 1.95 (m, 4H). 13C NMR
0
0
0
0
1H NMR (CDCl3):
d
8.50 (s, 1H, H6 ), 7.65 (dd, 1H, J5e4¼11.3 and
(CDCl3):
d
193.90(C1), 151.7 (C2 ), 150.7 (C3), 148.3 (C3 ), 143.8 (C5 or
0 00 0 00
J5e6¼14.7 Hz, H5), 7.51 (d, 1H, J2e3¼11.7, H2), 7.37 (d, 1H,
C
arom), 143.7 (C5 or Carom), 141.7 (C6 or C4 ), 141.5 (C6 or C4 ), 139.1

2296
N. Hebbar et al. / Tetrahedron 67 (2011) 2287e2298
00
00
0
50
00
arom
00
(C2 ), 137.9 (C5 ), 134.6 (C2 or C4), 134.5 (C2 or C4), 132.8 (C5), 129.2
(C300), 126.4 (Carom), 124.4 (Carom), 124.0 (C600), 123.7 (C100), 121.6
(Carom), 50.3 (Cjulo), 28.1 (Cjulo), 22.1 (Cjulo).
d
159.1 (C2), 151.9 (C ), 149.0 (C4), 143.9 (C
), 143.6 (C3 ), 143.4
0
0
200
(C2 ), 141.9 (C6 and C4 ),139.6 (C ),138.2 (C5 ),136.3 (C6),133.1 (C5),
00
00
129.3 (C3 or C3 ), 129.2 (C3 or C3 ), 126.4 (Carom), 124.3 (Carom), 124.0
00
00
(C6 ), 123.7 (C1 ), 121.6 (Carom), 113.9 (CCN), 111.9 (CCN), 83.8 (C1),
50.3 (Cjulo), 28.0 (Cjulo), 22.1 (Cjulo).
4.3.12. (2E,4E)-5-[30-Chloro-50[(100E,300E,500E)-600-(p-octyloxyphenyl)-
hexa-100,300,500-trienyl]pyrazin-20-yl]penta-2,4-dienal (11b). This com-
pound was obtained according to the general procedure A.
4.3.14. (3E,5E)-1,1-Dicyano-6[3-chloro-50-[(100E,300E,500E)-600-(p-octy-
loxyphenyl)-hexa-100,300,500-trienyl]pyrazin-20-yl]-hexa-1,3,5-triene
(12b). This compound was obtained according to the same pro-
cedure for 12a.
LTMP was prepared from anhydrous THF (40 mL), 2,2,6,6-tetra-
methylpiperidine (0.58 mL, 3.44 mmol, 4.2 equiv) and n-BuLi
(2.10 mL, 3.36 mmol, 4.1 equiv,1.6 M in hexanes) cooled at q1¼ꢀ78 ꢁC
and reacted with 10 (0.82 mmol, 1 equiv) in THF (20 mL) for
t1¼15 min, ZnCl2 (0.456 g, 3.36 mmol, 4.1 equiv) in anhydrous THF
(20 mL), 1-bromo-6-(p-octyloxyphenyl)hexa-1,3,5-triene (0.298 g,
0.82 mmol, 1 equiv) and Pd(PPh3)4 (0.048 g, 0.04 mmol, 5 mol %) in
V2¼THF (20 mL) for t2¼4 h. Hydrolysis was carried out with a 10%
aqueous solution of HCl (20 mL). After extraction and evaporation the
crude product was further purified by silica gel column chromatog-
raphy (dichloromethane/ethyl acetate: 20/1) to give a mixture of two
isomers (75/25). Yield: 0.199 g (51%) as a red solid. Mp¼194 ꢁC. IR:
3020, 2927, 2856, 2813,1674,1609,1587,1396,1371, 1318,1301, 1249,
1150, 1113, 812, 795, 725, 641, 615 cmꢀ1. MS (CI, isobutane) m/z:
477e479 (Mþ1, 22%, 5%), 476e478 (Mþ_, 35%,14%), 447(MꢀCHO,14%),
445(8%), 443(15%),441(MꢀCl,100%), 411(9%), 363(6%),194(10%), 57
(16%), 55(13%). Anal. Calcd for C29H33O2N2Cl(476.45): C 73.04, H 6.93,
Aldehyde 11b (101 mg, 0.21 mmol, 1.00 equiv), malononitrile
(14 mg, 0.21 mmol, 1.20 equiv),
0.01 equiv) ethanol (50 mL).
b-alanine (0.20 mg, 0.002 mmol,
Yield: 0.088 g (79%) as a purple solid. Mp¼219 ꢁC. IR: 3015,
2926, 2855, 2226, 1586, 1447, 1369, 1250, 1177, 938, 854, 833, 806,
722, 612 cmꢀ1. MS (EI) m/z: 524e526 (Mþ_, 34%, 10%), 479 (17%), 448
(24%), 386 (22%), 367 (9%), 336 (11%), 314 (29%), 264 (14%), 182
(31%), 149 (70%), 132 (51%), 121 (48%), 106 (96%), 69 (97%), 56
(100%). Anal. Calcd for C32H33ON4Cl (524.45): C 73.22, H 6.29, N
10.68; found: C 73.65, H 6.67, N 10.87.
0
1H NMR (CDCl3):
d
8.39 (s, 1H, H6 ), 7.63 (dd, 1H, J5e4¼11.3 and
200
J5e6¼14.7 Hz, H5), 7.54 (dd, 1H, J2 e3 ¼11.3 and J2 e1 ¼15.1 Hz, H ),
00
00
00
00
7.51 (d, 1H, J2e3¼11.7, H2), 7.38 (d, 1H, J6e5¼14.7 Hz, H6), 7.37 (d, 2H,
H
arom), 7.15 (dd, 1H, J4e3¼14.7 and J4e5¼11.3 Hz, H4), 6.95 (dd, 1H,
N 5.88; found: C 72.91, H 7.12, N 5.87.
J3e4¼14.7 and J3e2¼11.3 Hz, H3), 7.87 (d, 2H, Harom), 6.77 (d, 1H,
0
100
400
1H NMR (CDCl3):
d
9.68 (d, 1H, J1e2¼7.9 Hz, H1), 8.38 (s, 1H, H6 ),
J1 e2 ¼15.1 Hz, H ), 6.76(dd,1H, J4 e3 ¼14.7andJ4 e5 ¼10.6 Hz, H ),
00 00
600
00
00
00
00
00
00
7.65 (dd, 1H, J4e3¼11.3 and J4e5¼15.1 Hz, H4), 7.63 (dd, 1H,
6.67 (d, 1H, J6 e5 ¼15.1 Hz, H ), 6.56e6.47 (m, 2H, H3 and H5 ), 3.97
00
00
200
J2 e3 ¼11.3 and J2 e1 ¼15.1 Hz, H ), 7.40 (d, 1H, J5e4¼14.7 Hz, H5),
7.34 (dd, 1H, J3e4¼11.3 and J3e2¼15.1 Hz, H3), 7.36 (d, 2H, 2H,
J¼8.7 Hz, Harom), 6.86 (d, 2H, 2H, J¼8.70H0 z, Harom), 6.77 (d, 1H,
(t, 2H, J¼6.4 Hz), 2.74 (t, 4H, J¼6.4 Hz), 1.78 (m, 2H), 1.45e1.29 (m,
00
00
00
00
10H), 0.89 (t, 3H, J¼6.1 Hz). 13C NMR (CDCl3):
d
159.9 (Carom), 159.0
0
60
00
0
0
(C2), 151.5 (C5 ), 148.7 (C4), 148.6 (C3 ), 144.0 (C2 ), 142.0 (C ), 140.5
00
00
00
00
600
J6 5 ¼15.1 Hz, H ), 6.75e6.64 (m, 2H, H4 and H5 ), 6.50 (dd, 1H,
(C4 ), 138.9 (C2 ), 136.6 (C6), 136.0 (C5 ), 133.5 (C5), 131.1 (C3 ), 129.7
00 00
300
00
00
(Carom), 129.4 (C3), 128.5 (Carom), 126.6 (C6 ), 125.3 (C1 ), 115.1 (Carom),
113.8(CCN),111.8(CCN), 84.1 (C1),68.4,0.32.1, 29.7, 29.6, 26.4, 23.0,14.5.
00
00
00
00
00
00
J3 e4 ¼14.7 and J3 e2 ¼11.3 Hz, H ), 6.54 (d, 1H, J1 e2 ¼14.7 Hz,
00
H1 ), 6.40 (dd, 1H, J2e1¼7.9 and J2e3¼15.1 Hz, H2), 3.96 (t, 2H,
J¼6.1 Hz),1.78 (m, 2H),1.45e1.29 (m,10H), 0.89 (t, 3H, J¼6.1 Hz). 13C
0
NMR (CDCl3): 0
d
193.5 (C1), 159.5 (Carom), 150.9 (C2 ), 150.1 (C300 ), 147.9
40.03.15. 2-Chloro-6-[(1000E,300E,5000E)-600-(p-octyloxyphenyl)-hexa-100-
0
0
00
00
(C3 ), 143.9 (C5 ), 141.4 (C6 ), 139.8 (C4 ), 138.1 (C2 ), 135.9 (C5 ), 134.1
(C2 or C4), 133.9 (C2 or C4), 132.9 (C5), 130.8 (C300), 129.4 (Carom),
128.1 (Carom), 126.3 (C600), 125.0 (C100), 114.8 (Carom), 68.1, 0.31.8,
29.3, 29.2, 26.0, 22.6, 14.1.
3 -5 -trienyl]-3-[(1 E,3 E,5 E)-6 -(p-trifluoromethylphenyl)-hexa-1 -
300-500-trienyl]pyrazine (13). To a solution of phosphonium salt
(0.46 mmol, 1.2 equiv) in THF (40 mL) at 0 ꢁC under an argon atmo-
sphere, was slowly added n-BuLi (1.6 M in hexane, 0.46 mmol,
1.2 equiv). After 30 min stirring, aldehyde 11 (0.38 mmol,1.0 equiv) in
THF (20 mL) was slowly added. The reaction mixture was stirred for
10 min at 0 ꢁC and 5 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
(3ꢂ15 mL). The combined organic extracts were washed with satu-
rated brine (10 mL) and dried over MgSO4. Afterevaporation thecrude
product was further purified by silica gel column chromatography
(pentane/dichloromethane: 35/10)to give amixture of two isomers(Z,
E). The isomerization was realized by 10 mol % of iodine in refluxing
dichloromethane or toluene during 4 h. A solution of sodium thio-
sulfate was added and after extraction with dichloromethane
(2ꢂ15 mL) the combined organic extracts were dried over MgSO4.
After evaporation, only isomer all E was obtained with good purity.
Yield: 0.111 g (47%) as a purple solid. Mp¼170 ꢁC. IR: 3019, 2953,
2924, 2867, 2846, 1611, 1584, 1449, 1423, 1391, 1250, 1176, 1124, 915,
868, 853, 724, 616 cmꢀ1. MS (EI) m/z: 618e620 (Mþ_, 16%, 5%), 540
(9%), 426 (15%), 389 (21%), 285 (29%), 233 (34%), 192 (67%), 172
(71%), 142 (37%), 107 (100%), 92 (99%), 74 (44%), 55 (51%). Anal.
Calcd for C37H38ON2F3Cl (618.45): C 71.79, H 6.14, N 4.53; found: C
71.46, H 6.12, N 4.49.
00
0
0
00
ꢀ
4.3.13. (3E,5E)-1,1-Dicyano-6-[30-chloro-50-[(100E,300E,500E)-600-(9000-
julolidinyl)-hexa-100,300,500-trienyl]
(12a). A mixture of aldehyde 11a (350 mg, 0.79 mmol, 1.00 equiv),
malononitrile (63 mg, 0.95 mmol, 1.20 equiv) and -alanine
pyrazin-20-yl]-hexa-1,3,5-triene
b
(0.70 mg, 0.008 mmol, 0.01 equiv) was stirred at 60 ꢁC for 20 h in
ethanol (100 mL) under an argon atmosphere. The ethanol was
removed under vacuum and water was added (20 mL). The
resulting solution was then extracted with dichloromethane
(3ꢂ15 mL) and the combined organic extracts were dried over
MgSO4. After evaporation the crude product was recrystallized
from ethanol.
Yield: 0.314 g (81%) as a brown solid. Mp>260 ꢁC. IR: 3440,
2938, 2841, 2222, 2169, 2113, 1583, 1312, 1206, 1181, 1167, 1127,
1063, 996, 893 cmꢀ1. MS (EI) m/z: 491e493 (Mþ_, 30%, 9%), 446
(11%), 415 (34%), 353 (13%), 334 (11%), 303 (11%), 281 (36%), 250
(35%), 231 (19%), 149 (31%), 156 (59%), 136 (70%), 116 (67%), 84
(78%), 56 (100%). Anal. Calcd for C30H26N5Cl (491.45): C 73.25, H
5.29, N 14.24; found: C 73.31, H 5.37,0N 14.33.
1H NMR (CDCl3):
d
8.37 (s, 1H, H6 ), 7.61 (dd, 1H, J5e4¼11.3 and
200
J5e6¼14.7 Hz, H5), 7.57 (dd, 1H, J2 e3 ¼11.3 and J2 e1 ¼15.1 Hz, H ),
7.53 (d,1H, J2e3¼11.7, H2), 7.39 (d,1H, J6e5¼14.7 Hz, H6), 7.16 (dd,1H,
J4e3¼14.7 and J4e5¼11.3 Hz, H4), 6.95 (dd, 1H, J3e4¼14.7 and
00
00
00
00
1H NMR (CDCl3):
d
0
8.33 (s, 1H, H5), 7.55 (d, 2H, Harom), 7.51 (dd,
20
1H, J2 e3 ¼10.2 and J2 e1 ¼15.1 Hz, H ), 7.46 (d, 2H, Harom), 7.44 (dd,
0
0
0
200
J3ee2¼11.3 Hz, H3), 6.91 (s, 2H, Harom), 6.75 (d, 1H, J1 e2 ¼15.1 Hz,
1H, J2 e3 ¼11.3 and J2 e1 ¼15.1 Hz, H ), 7.33 (d, 2H, Harom), 7.01 (d,
00
00
00
00
00
00
00
400
10
H1 ), 6.68 (dd, 1H, J4 e3 ¼14.7 and J4 e5 ¼10.6 Hz, H 00 ), 6.58 (d, 1H,
1H, J1 e2 ¼14.7 Hz, H ), 6.95 (dd, 1H, J5 e4 ¼11.300and00J5 e6 ¼15.1 Hz,
00
00
00
00
0
0
0
0
0
0
00
0
00
0
0
600
J6 e5 ¼15.1 Hz, H ), 6.51e6.40 (m, 2H, H3 and H5 ), 3.20 (t, 4H,
H5 ), 6.83 (d, 2H, Harom), 6.77e6.59 (m, 6H, H1 , H4 , H6 , H6 , H3 ,
00
00
0
00
00
J¼5.7 Hz), 2.74 (t, 4H, J¼6.4 Hz), 1.95 (m, 4H). 13C NMR (CDCl3):
H4 ), 6.56e6.47 (m, 2H, H5 , H3 ), 3.97 (t, 2H, J¼6.4 Hz), 3.93 (t, 2H,

N. Hebbar et al. / Tetrahedron 67 (2011) 2287e2298
2297
J¼6.4 Hz), 1.75 (m, 2H), 1.42e1.269 (m, 10H), 0.85 (t, 3H, J¼6.4 Hz).
general procedure B. LTMP was prepared from TMPH (0.56 mL,
3.3 mmol, 2.4 equiv), n-BuLi (2.0 M in hexanes, 1.6 mL, 3.2 mmol,
2.3 equiv) in THF (40 mL), cooled at ꢀ100 ꢁC and treated with 6,60-
dichloro-2,20-bipyrazine 14 (310 mg, 1.4 mmol, 1.0 equiv) in THF
(20 mL) for t1¼5 min. The electrophile was 4-methox-
ybenzaldehyde (0.56 g, 4.1 mmol, 3.0 equiv) in THF (20 mL) at
ꢀ100 ꢁC to ꢀ78 ꢁC in 2 h. Hydrolysis was carried out with water
(20 mL). Eluent for chromatography: ethyl acetate/dichloro-
methane (1/10). Yield: 0.430 g (63%) mixture of diastereomer as
a yellow solid. Mp¼242 ꢁC. IR: 3476, 3076, 3009, 2955, 2897, 2837,
1609, 1584, 1387, 1251, 1039, 930, 869, 794, 757, 579 cmꢀ1. MS (EI)
m/z: 498e500e502 (Mþ_, 14%), 465 (11%), 433 (16%), 380 (16%), 367
(20%), 344 (23%), 321 (21%), 290 (31%), 275 (45%), 219 (30%), 191
(38%), 177 (73%), 152 (38%), 139 (66%), 96 (66%), 73 (100%). Anal.
Calcd for C24H20O4Cl2N4 (498.9): C 57.73, H 4.01, N 11.22; found: C
13C NMR (CDCl3):
d
159.7 (Carom00 ), 149.5 (C6), 147.3 (C20 ), 146.1 (C30),
0 00
141.5 (C5), 140.8 (C100 ), 139.1 (C4 0 ), 137.5 (C20 ), 136.900(C4 ), 136.7 0(C2 ),
135.6 (C5), 134.6 (C5 ), 133.4 (C3 ), 131.4 (C6 and C3 ), 131.3 (C6 and
00
C3 )00, 129.7 (Carom), 128.4 (Carom), 127.1 (Carom), 127.0 (Carom), 126.8
0
00
(C6 ), 126.3 (C1 ), 126.0 (C1 ), 125.8 (Carom), 122.7 (CF3), 115.1 (Carom),
68.4, 32.2, 29.7, 29.6, 26.4, 23.0, 14.5. 19F NMR (CDCl3):
d
ꢀ63.0.
4.3.16. 6,60-Dichloro-2,20-bipyrazine (14). A solution of 2-chloro-6-
iodopyrazine (466 mg, 1.94 mmol) and 2-chloro-6-tributyl-
stannylpyrazine (782 mg, 1.94 mmol) in anhydrous toluene (100 mL)
was degassed and placed under an argon atmosphere. Tetrakis(tri-
phenylphosphine)palladium[0] (112 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 over MgSO4 and evaporated under reduced pressure. The crude
product was further purified by silica gel column chromatography
(pentane/ethyl acetate: 70/30). Yield: 0.418 g (95%) as a white solid.
Mp¼240 ꢁC. IR: 3122, 3057, 2957, 2933, 2868, 1375, 1345, 1199, 1147,
908, 887, 766, 742, 511 cmꢀ1. MS (EI) m/z: 226e228-230 (Mþ_, 95%,
93%, 19%), 201 (22%), 199 (24%), 138 (45%), 108 (24%), 104 (22%), 104
(21%), 89 (45%) 87 (100%), 78 (29%). Anal. Calcd for C8H4N4Cl2 (226.9):
57.48, H 3.95, N 11.25.
0
1H NMR (CDCl3):
d
9.45 (s, 2H, H3 and H3 ), 7.29 (d, 2H, J¼8.7 Hz,
H
arom), 6.87 (d, 2H, J¼8.7 Hz, Harom), 6.05 (d, 2H, J¼7.9 Hz), 4.58 (d,
2H, J¼7.9 Hz, OH), 3.79 (s, 6H, CH3). 13C NMR (CDCl3):
d 160.0
0
0
0
(Carom), 156.0 (C5 and C5 ), 146.9 (C2 and C2 or C6 and C6 ), 146.8 (C2
0
0
0
and C2 or C6 and C6 ), 139.8 (C3 and C3 ), 132.5 (Carom), 129.2 (Carom),
114.5 (Carom), 72.2 (COH), 55.6 (CH3).
C 42.31, H 1.76, N 24.28; found: C 42.14, H 1.78, N 24.59.
4.3.20. (200E,400E)-Bis[6-chloro-5-(penta-200,400-dienal)]-2,20-bipyr-
azine (18). This compound was obtained according to the general
procedure A. LTMP was prepared from anhydrous THF (80 mL),
2,2,6,6-tetramethylpiperidine (0.54 mL, 3.17 mmol, 2.4 equiv) and
n-BuLi (1.60 mL, 3.04 mmol, 2.3 equiv 1.91 M in hexanes) cooled at
q1¼ꢀ100 ꢁC and reacted with 6,60-dichloro-2,20-bipyrazine 14
(1.32 mmol, 1 equiv) in THF (20 mL) for t1¼5 min, ZnCl2 (0.722 g,
5.28 mmol, 4.0 equiv) in anhydrous THF (20 mL), 5-bromo-penta-
2,4-dienal (0.427 g, 2.64 mmol, 2.0 equiv) and Pd(PPh3)4 (0.152 g,
0.13 mmol, 10 mol %) in V2¼THF (30 mL) for t2¼5 h. The crude
product was recrystallized from dichloromethane. Yield: 0.328 g
(64%) as a yellow solid. Mp>260 ꢁC. IR: 3054, 2970, 2846, 1680,
1619, 1490, 1423, 1300, 1150, 1099, 1065, 1019, 996, 878, 802, 748,
693, 524 cmꢀ1. MS (EI) m/z: 386e388-390 (Mþ_, 14%, 5%), 346 (9%),
314 (17%), 291 (20%), 281 (27%), 221 (17%), 213 (22%), 197 (23%), 189
(24%), 163 (29%), 142 (19%), 129 (40%), 107 (96%), 106 (100%), 91
(62%), 79 (74%), 57 (71%). Anal. Calcd for C18H12O2N4Cl2 (386.9): C
0
1H NMR (CDCl3):
d
9.45 (s, 2H, H3 and H3 ), 8.68 (s, 2H,0 H5 and
0
0
H5 ). 13C NMR (CDCl3):
d
149.0 (C6 and C6 ), 147.9 (C2 and C2 ), 146.0
0
0
(C5 and C5 ), 141.3 (C3 and C3 ).
4.3.17. 5,50-Dideuterio-6,60-dichloro-2,20-bipyrazine (15). This com-
pound has been obtained according to general procedure B. LTMP
was prepared from TMPH (0.54 mL, 3.20 mmol, 2.4 equiv), n-BuLi
(2.12 M in hexanes, 1.44 mL, 3.10 mmol, 2.3 equiv) in THF (40 mL),
cooled at ꢀ100 ꢁC and treated with 6,60-dichloro-2,20-bipyrazine 14
(300 mg, 1.30 mmol, 1.0 equiv) in THF (15 mL) for t1¼5 min. The
electrophile was EtOD (0.8 mL, 13.00 mmol, 10.0 equiv) in THF
(10 mL) at ꢀ100 ꢁC for 30 min. Hydrolysis was carried out with water
(20 mL). Eluent for chromatography: dichloromethane. Yield: 0.212 g
(70%) as a white solid. Mp¼242 ꢁC. IR: 3115, 3065, 1550, 1380, 1149,
1092, 1030, 960, 900, 763, 672, 626 cmꢀ1. MS (EI) m/z: 228e230-232
(Mþ_, 100%, 58%, 10%), 200 (10%), 193 (12%), 141 (29%), 139 (34%), 114
(19%), 88 (39%), 61 (42%). Anal. Calcd for C8H2D2N4Cl2 (228.9): C
55.83, H 3.10, N 14.47; found: C 56.01, H 3.21, N 14.68.
100
1H NMR (CDCl3):
d
9.73 (d, 2H, J1 e2 ¼7.5 Hz, H ), 9.45 (s, 2H, H3
00
00
41.94, H 0.87, N 24.46; found: C 41.37, H 1.39, N 24.10.
0
0
400
1H NMR (CDCl3):
d
9.45 (s, 2H, H3 and H3 ). 13C NMR (CDCl3):
and H3 ), 7.84 (dd, 2H, J4 e3 ¼11.3 and J4 e3 ¼11.3 Hz, H ), 7.45 (d,
00
00
00
00
0
0
0
500
149.0 (C6 and C6 ), 147.9 (C2 and C2 ), 146.0 (C5 and C5 ), 141.3 (C3
2H, J5 e4 ¼15.1 Hz, H ), 7.39 (dd, 2H, J3 e4 ¼11.3 and J3 e2 ¼15.1 Hz,
00
00
00
00
00
00
d
0
00
200
and C3 ).
H3 ), 6.48 (dd, 2H, J2 e1 ¼7.5 and J2 e3 ¼15.1 0Hz, H ). 13C NMR
00
00
00
00
00
00
60
(CDCl3):
d
193.70(C1 ),149.5 (C3 ),0148.5 (C5and C5 ),147.8 (C6 and C ),
00 00 00
4.3.18. 5,50-Di(tributylstannyl)-6,60-dichloro-2,20-bipyrazine
(16). This compound has been obtained according to general pro-
cedure B. LTMP was prepared from TMPH (0.38 mL, 2.20 mmol,
2.4 equiv), n-BuLi (1.84 M in hexanes,1.15 mL, 2.10 mmol, 2.3 equiv)
in THF (40 mL), cooled at ꢀ100 ꢁC and treated with 6,60-dichloro-
2,20-bipyrazine 14 (209 mg, 0.90 mmol, 1.0 equiv) in THF (15 mL)
for t1¼5 min. The electrophile was Bu3SnCl (0.63 mL, 2.30 mmol,
2.5 equiv) in THF (10 mL) at ꢀ100 ꢁC to ꢀ78 ꢁC in 3 h. Hydrolysis
was carried out with water (20 mL). Eluent for chromatography:
pentane/dichloromethane (9/1). Yield: 0.301 g (41%) as a colourless
oil. IR: 2955, 2920, 2852, 1523, 1464, 1240, 1139, 1076, 1037, 781,
694, 638 cmꢀ1. Anal. Calcd for C32H56N4Sn2 (733.42): C 47.74, H
146.7 (C2 and C2 ),141.7 (C3 and C3 ),136.0 (C2 ),135.5 (C4 ),133.3 (C5 ).
4.3.21. 6,60-Dichloro-5,50-bis[600-(9000-julolidinyl)-(100E,300E,500E)-hexa-
100,300,500-trienyl]-2,20-bipyrazine (19). This compound was obtained
according to the general procedure A. LTMP was prepared from
anhydrous THF (80 mL), 2,2,6,6-tetramethylpiperidine (0.45 mL,
2.64 mmol, 2.4 equiv) and n-BuLi (1.30 mL, 2.53 mmol, 2.3 equiv,
1.94 M in hexanes) cooled at q1¼ꢀ100 ꢁC and reacted with 6,60-
dichloro-2,20-bipyrazine 14 (1.10 mmol, 1 equiv) in THF (20 mL) for
t1¼5 min, ZnCl2 (0.722 g, 4.40 mmol, 4.0 equiv) in anhydrous THF
(20 mL),1-bromo-6-julolidinylhexa-1,3,5-triene (0.727 g, 2.20 mmol,
2.0 equiv) and Pd(PPh3)4 (0.127 g, 0.11 mmol, 10 mol %) in V2¼THF
(30 mL) for t2¼5 h. The crude product was recrystallized from
dichloromethane.
6.96, N 6.96; found: C 47.62, H 6.88, N 6.85.
0
1H NMR (CDCl3):
d
9.52 (s, 2H, H3 and H3 ), 1.63e1.52 (m, 12H),
1.39e1.23 (m, 24H), 0.87 (t 18H). 13C NMR (CDCl3):
d
173.9 (C5 and
Yield: 0.451 g (57%) as a purple solid. Mp>260 ꢁC. IR: 3020,
2938, 2841, 1568, 1311, 1237, 1203, 1135, 1061, 998, 845 cmꢀ1. MS
(EI) m/z: 724e726-728 (Mþ_, 18%, 6%), 476 (40%), 444 (15%), 372
(21%), 281 (27%), 163 (15%), 129 (35%), 106 (66%), 83 (43%), 57
(100%). Anal. Calcd for C44H42N6Cl2 (724.9): C 72.83, H 5.79, N 11.59;
found: C 72.97, H 5.85, N 11.65.
0
0
0
0
C5 ), 156.7 (C6 and C6 ), 146.6 (C2 and C2 ), 141.8 (C3 and C3 ), 29.3,
27.6, 14.0, 11.3.
4.3.19. 5,50-Bis(p-methoxyphenylhydroxymethyl)-6,60-dichloro-2,20-
bipyrazine (17). This compound has been obtained according to

2298
N. Hebbar et al. / Tetrahedron 67 (2011) 2287e2298
1H NMR (CDCl3):
d
9.27 (s, 2H, H3), 7.73 (dd, 2H, J2 e3 ¼11.3 and
(d) Conjugated Polymers; Bredas, J. L., Sylbey, R., Eds.; Kluwer: Dordrecht, The
Netherlands, 1991; (e) Roncali, J. Chem. Rev. 1992, 92, 711; (f) Gustafsson, G.; Cao,
Y.; Treacy, G. M.; Klavetter, F.; Colaneri, N.; Heeger, A. J. Nature 1992, 357, 477;
(g) Hide, F.; Diaz-Garcia, M. A.; Schwartz, B. J.; Heeger, A. J. Acc. Chem. Res. 1997,
30, 430; (h) Kraft, A.; Grimsdale, A. C.; Holmes, A. B. Angew. Chem., Int. Ed. 1998,
37, 402; (i) Bernius, M. T.; Inbasekaran, M.; O0Brien, J.; Wu, W. S. Adv. Mater. 2000,
12, 1737; (j) Ho, P. K. H.; Kim, J. S.; Burroughes, J. H.; Becker, H.; Li, S. F. Y.; Brown,
00
00
200
8000
10000
00
00
J2 e1 ¼15.1 Hz, H ), 6.91 (s, 4H, H
and H ), 6.83 (d, 2H,
100
00
00
00
00
00
00
J1 e2 ¼15.1 Hz, H ), 6.69 (dd, 2H, J4 e5 ¼10.6 and J4 e3 ¼14.3 Hz,
00
600
H4 ), 6.60 (d, 2H, J6 e5 ¼15.1 Hz, H ), 6.52 (dd, 2H, J5 e4 ¼10.6 and
00
00
00
00
500
00
00
00
00
00
00
J5 e6 ¼15.1 Hz, H ), 6.47 (dd, 2H, J3 e2 ¼11.3 and J3 e4 ¼14.3 Hz,
00
H3 ), 3.17 (t, 8H, J¼5.7 Hz), 2.73 (t, 8H, J¼6.4 Hz), 1.98 (m, 8H). 13
C
€
T. M.; Cacialli, F.; Friend, R. H. Nature 2000, 404, 481; (k) Gross, M.; Muller, D. C.;
0
50
NMR (CDCl3):
d
150.3 (C5and C ), 146.5 (C6 and C6 ), 144.1 (C2 and
€
Nothofer, H.-G.; Scherf, U.; Neher, D.; Brauchle, C.; Meerholz, K. Nature 2000,
400
0
0
0
0
0
0
0
0
C2 ), 142.4 (C3 and C3 ),144.1 (C6 ), 141.4 (C ),140.6 (C200 ), 138.1 (C500),
405, 661; (l) Kulkarni, A. P.; Tonzola, C. J.; Babel; Jenekhe, S. A. Chem. Mater. 2004,
16, 4556; (m) Hughes, G.; Bryce, M. R. J. Mater. Chem. 2005, 15, 94.
2. (a) Albinsson, B.; Eng, M. P.; Petterson, K.; Winters, M. U. Phys. Chem. Chem.
Phys. 2007, 9, 5847; (b) Meyer, H. Angew. Chem. Int. Ed. 2005, 44, 2482; (c) Kim,
E.; Park, S. B. Chem. Asian J. 2009, 4, 1646.
00
000
000
000
130.1 (C3 ), 126.7 (C8 and C10 ), 124.3 (C9 ), 123.0 (0C00 6 ), 122.1 (C1 ),
000
000
000
000
122.0 (C5 and C7 ), 50.3 (C2 ), 28.0 (C4 ), 22.2 (C3 ).
3. (a) He, G. S.; Tan, L.-S.; Zheng, Q.; Prasad, P. N. Chem. Rev. 2008, 106, 1245;
(b) Pawlicki, M.; Collins, H. A.; Denning, R. G.; Anderson, H. L. Angew. Chem., Int.
Ed. 2009, 48, 3244; (c) Kim, H. M.; Cho, B. R. Chem. Commun. 2009, 153.
4. (a) Denk, W.; Strickler, J. H.; Webb, W. W. Science 1990, 248, 73; (b) Zipfel, W. R.;
Williams, R. M.; Webb, W. W. Nat. Biotechnol. 2003, 21, 1369.
5. (a) He, G. S.; Bhawalkar, J. D.; Zhao, C. F.; Prasad, P. N. Appl. Phys. Lett. 1995, 67,
2433; (b) Lei, H.; Huang, Z. L.; Wang, H. Z.; Tang, X. J.; Wu, L. Z.; Zhou, G. Y.;
Wang, D.; Tian, Y. B. Chem. Phys. Lett. 2002, 352, 240; (c) Silly, M. G.; Porres, L.;
Mongin, O.; Chollet, P. A.; Blanchard-Desce, M. 2003, 379, 74.
6. (a) Bhawalkar, J. D.; Kumar, N. D.; Zhao, C. F.; Prasad, P. N. J. Clin. Laser Med. Surg.
1997, 15, 201; (b) Ogawa, K.; Hasegawa, H.; Inaba, Y.; Kobuke, Y.; Inouye, H.;
Kanemitsu, Y.; Kohno, E.; Hirano, T.; Ogura, S.; Okura, I. J. Med. Chem. 2006, 49,
2276.
7. (a) Parthenopoulos, D. A.; Rentzepis, P. M. Science 1989, 245, 843; (b) Corredor,
C. C.; Huang, Z. L.; Belfield, K. D. Adv. Mater. 2006, 18, 2910.
4.3.22. (100E,300E,500E)-6,60-Dichloro-5,50-bis[600-(p-n-octyloxyphenyl)-
hexa-100,300,500-trienyl]-2,20-bipyrazine (20). This compound was
obtained according to the same procedure as for 13. Phosphonium
salt (2.17 mmol, 2.4 equiv), THF (100 mL), n-BuLi (2.4 M in hexane,
2.17 mmol, 2.4 equiv), dialdehyde 18 (0.90 mmol, 1.0 equiv), THF
(20 mL), 16 h at room temperature. The crude product was further
purified by recrytallization from dichloromethane. The isomeriza-
tion was realized by 10 mol % of iodine in refluxing dichloromethane.
Yield: 0.530 g (74%) as a red solid. Mp¼255 ꢁC. IR: 3295, 3003,
2953,2921, 2858,1585,1476,1414,1304,1264,1242, 996, 860,837, 799,
742, 619 cmꢀ1. MS (EI) m/z: 790e792-794(Mþ_, 4%), 548 (4%), 475(6%),
402 (5%), 376 (9%), 328 (6%), 285 (7%), 279 (11%), 224 (21%),175 (20%),
130 (77%),106 (100%), 72 (56%). Anal. Calcd for C48H56O2N4Cl2 (790.9):
C 73.83, H 7.08, N 7.08; found: C 73.94, H 7.15, N 7.11.
8. (a) Zhou, W. H.; Kuebler, S. M.; Braun, K. L.; Yu, T.; Cammack, J. K.; Ober, C. K.;
Perrer, J. W.; Marder, S. R. Science 2002, 296, 1106; (b) Chen, Y. S.; Tal, A.; Tor-
rance, D. B.; Kuebler, S. M. Adv. Funct. Mater. 2006, 16, 1739.
ꢀ
ꢀ
9. Hebbar, N.; Ramondenc, Y.; Ple, G.; Dupas, G.; Ple, N. Tetrahedron 2009, 65, 4190.
10. Wang, H.; Lu, Z.; Lord, S. J.; Willets, K. A.; Bertke, J. A.; Bunge, S. D.; Moerner, W.
E.; Twieg, R. J. Tetrahedron 2007, 63, 103.
1H NMR (CDCl3):
d
9.32 (s, 2H, H3), 7.73 (dd, 2H, J2 e3 ¼11.3 and
00
00
200
100
600
J2 e1 ¼15.1 Hz, H ), 7.38 (d, 4H, J¼8.7 Hz, Harom), 7.02 (d, 2H,
00
00
11. Cai, G. L.; Bozhkova, N.; Odingo, J.; Berova, N.; Nakanishi, K. J. Am. Chem. Soc.
1993, 115, 7192.
12. (a) Giacomelli, G.; Lardicci, L.; Saba, A. J. Chem. Soc., Perkin Trans. 1 1978, 314;
(b) Saltiel, J.; Ganapathy, S.; Werking, C. J. Phys. Chem. 1987, 91, 2555;
(c) Gaukroger, K.; Hadfield, J. A.; Hepworth, L. A.; Lawrence, N. J.; Mc Gown, A. T.
J. Org. Chem. 2001, 66, 8135.
J1 e2 ¼14.7 Hz, H ), 6.88 (d, 4H, J¼8.7 Hz, Harom), 6.87 (d, 2H,
00
00
00
00
00
00
00
00
J6 e5 ¼15.1 Hz, H ), 6.75 (dd, 2H, J4 e5 ¼11.3 and J4 e3 ¼15.1 Hz,
00
500
H4 ), 6.69 (dd, 2H, J5 e4 ¼10.9 and J5 e6 ¼15.1 Hz, H ), 6.59 (dd, 2H,
00
00
00
00
300
00
00
00
00
J3 e2 ¼11.3 and J3 e4 ¼14.7 Hz, H ), 3.97 (t, 4H, J¼6.1 Hz), 1.78 (m,
4H). 1.45e1.29 (m, 20H), 0.89 (t, 6H, J¼6.4 Hz). 13C NMR (CDCl3):
ꢀ
ꢀ
13. (a) Ple, N.; Turck, A.; Heynderickx, A.; Queguiner, G. Tetrahedron 1998, 54, 4899;
0
0
d
159.8 (Carom), 150.2 (C5and C5 ), 146.4 (C6 and C6 ), 144.2 (C2 and
ꢀ
ꢀ
(b) Toudic, F.; Ple, N.; Turck, A.; Queguiner, G. Tetrahedron 2002, 58, 283;
(c) Toudic, F.; Heynderickx, A.; Ple, N.; Turck, A.; Queguiner, G. Tetrahedron
2003, 59, 6375.
20
30
400
200
500
ꢀ
ꢀ
C ), 142.5 (C3 and C ), 140.4 (C ), 139.9 (C ), 136.2 (C 00 ), 131.6
ˇ
00
00
(C3 ), 129.8 (Carom), 128.5 (Carom), 126.8 (C6 ), 124.0 (C1 ), 115.1
(Carom), 68.5, 32.2, 29.7, 29.6, 26.4, 23.0,14.5.
14. Linker, F.; Kreher, D.; Attias, A.-J.; Do, J.; Kim, E.; Haplot, P.; Lemaõtre, N.;
Geffroy, B.; Ulrich, G.; Ziessel, R. Inorg. Chem. 2010, 49, 3991.
15. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.;
Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin, K. N.; Burant, J. C.;
Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.;
Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.;
Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao,
O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Adamo, C.;
Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.;
Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.;
Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.;
Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J.
V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.;
Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-
Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.;
Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian 03,
Revision C.02; Gaussian: Wallingford CT, 2004; This package has been
implemented on a power-575 IBM cluster, This package has been implemented
on a power-575 IBM cluster. We thank the Centre de Ressources Informatiques
de Haute-Normandie (CRIHAN) for software optimization and technical support.
Acknowledgements
We thank Mr. Sigismund Melissen for performing the DFT cal-
culations. We thank the Centre de Ressources Informatiques de
Haute-Normandie (CRIHAN) for software optimization, technical
support and computation time donated on the IBM cluster.
References and notes
1. (a) Burroughes, J. H.; Bradley, D. D. C.; Brown, A. R.; Marks, R. N.; Mackay, K.;
Friend, R. H.; Burn, P. L.; Holmes, A. B. Nature 1990, 347, 539; (b) Handbook of
Conducting Polymers, 2nd ed.; Skotheim, T. A., Ed.; Dekker: New York, NY, 1997;
(c) Conjugated Conducting Polymers; Kies, H., Ed.; Springer: Berlin,1992; Vol.102;