Influence of thiazole regioisomerism on second-order nonlinear optical chromophores

Article abstract of DOI:10.1016/j.tet.2012.05.123

Two series of matched and mismatched donor-thiazole-acceptor chromophores have been synthesized to disclose the role that the orientation of the thiazole ring plays on their second-order nonlinear optical (NLO) properties. Whereas previous theoretical stu

Full text of DOI:10.1016/j.tet.2012.05.123

Tetrahedron 68 (2012) 6427e6437
Contents lists available at SciVerse ScienceDirect
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journal homepage: www.elsevier.com/locate/tet
Influence of thiazole regioisomerism on second-order nonlinear optical
chromophores
a
a
,
a
a
a
b
*
ꢀ
ꢀ
ꢀ
Elena Galan , Raquel Andreu , Javier Garín , Laura Mosteo , Jesus Orduna , Belen Villacampa ,
Beatriz E. Diosdado c
a
ꢀ
Departamento de Química Organica, Facultad de Ciencias-ICMA, Universidad de Zaragoza-CSIC, Pedro Cerbuna 12, E-50009 Zaragoza, Spain
b Departamento de Física de la Materia Condensada, ICMA, Universidad de Zaragoza-CSIC, 50009 Zaragoza, Spain
c
ꢀ
ꢀ
Servicio de Difraccion de Rayos X y Analisis por Fluorescencia, ICMA, Universidad de Zaragoza-CSIC, 50009 Zaragoza, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 24 April 2012
Received in revised form 24 May 2012
Accepted 29 May 2012
Available online 4 June 2012
Two series of matched and mismatched donorethiazoleeacceptor chromophores have been synthesized
to disclose the role that the orientation of the thiazole ring plays on their second-order nonlinear optical
(NLO) properties. Whereas previous theoretical studies predict that the matched systems show markedly
higher NLO responses, our experimental results do not parallel this trend, showing differences between
regioisomers much lower than those predicted.
Ó 2012 Elsevier Ltd. All rights reserved.
Dedicated to Dra. Nuria Gallego-Planas for
her friendship, enthusiasm, support and
inspiration while she was with us
Keywords:
Nonlinear optics
Thiazole
Regioisomerism
1. Introduction
thiazole is linked to the acceptor and the electron-rich 5-position to
the donor) or the mismatched one (in the opposite situation).
Second-order nonlinear optical (NLO) materials based on
donore -spacereacceptor (De eA) chromophores have been
developed for the last two decades in both academia and industry.1
Among the traditional -spacers, polyenes allow for efficient
intramolecular charge transfer (ICT) from donor to acceptor, but
they impart low thermal and chemical stabilities, whereas the re-
verse situation is found for aryl-type spacers.
The required balance between stability and charge de-
localization was not reached until the replacement of aryl rings
with the more easily delocalizable heteroaromatic rings was ex-
plored later on.2,3 In this way, and taking into account the low ar-
omatic delocalization energy (ADE) of thiazole (25 kcal/mol) with
respect to that of benzene (36 kcal/mol),4 considerable interest has
N
S
N
A
S
p
p
D
A
D
p
matched
mismatched
Breitung et al.3 first, and other authors later on,2c,5,6 carried out
theoretical calculations showing that the regioisomerism of
thiazole-containing chromophores significantly modulates the first
hyperpolarizability (b), with considerably better second-order NLO
properties being predicted for the matched derivatives.
Unfortunately, most thiazole-containing NLO chromophores
hitherto described are mismatched compounds7,47 and only a few
matched derivatives bearing either aromatic,8e11 or quinoidal
thiazoles12e17 have been reported.
Consequently, the effect of thiazole regioisomerism on second-
order NLO properties has been scantly studied experimentally. As
far as we know, there are only four pairs of analogous matched/
mismatched thiazole derivatives for which their second-order NLO
properties have been compared9,10,18 and the matched derivatives
been focused on DepeA chromophores bearing a thiazole spacer,
for which, due to its unsymmetrical nature, two regioisomers
should be considered. They are usually referred to as showing the
matched orientation (when the electron-poor 2-position of the
* Corresponding author. Tel.: þ34 976762282; fax: þ34 976761194; e-mail ad-
ꢀ
dresses: egalan@unizar.es (E. Galan), randreu@unizar.es (R. Andreu), jgarin@uni-
show only slightly enhanced
theoretical studies.
b values, at variance with previous
zar.es (J. Garín), laura_trzna7@hotmail.com (L. Mosteo), jorduna@unizar.es (J.
Orduna), bvillaca@unizar.es (B. Villacampa), diosdado@unizar.es (B.E. Diosdado).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.05.123

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E. Galan et al. / Tetrahedron 68 (2012) 6427e6437
6428
To get a better understanding of the role that the orientation of
donor and acceptor groups. Experimental NLO measurements are
compared to the results of theoretical calculations.
thiazole plays on the experimental second-order NLO properties of
DethiazoleeA chromophores, in this paper we describe the syn-
thesis, characterization and study of a series of comparable
matched/mismatched thiazole derivatives 1e10, bearing different
2. Results and discussion
2.1. Synthesis
Et
O
N
S
Compounds 1e6, with a piperidine moiety as a donor were
prepared through a three-step synthesis, as shown in Scheme 1.
Mismatched aldehyde 16a19 was prepared by lithiation of 1420
followed by reaction with DMF (17a).21 An analogous reaction us-
ing (E)-3-dimethylaminoacrylaldehyde (17b) gave the new alde-
hyde 16b. Unlike 14, 5-piperidinothiazole 13 has not been
previously reported. This compound cannot be prepared by nu-
cleophilic aromatic substitution of 5-bromothiazole with piperi-
dine,22 but, to our delight, a Rh-catalyzed version of this reaction23
gave 13 in excellent yield. Matched aldehydes 15a,b were prepared
analogously to 16a,b, but starting from 13.
X Y
S
CN
CN
X Y
S
NEt
N
N
n
n
O
1a-b; 2a-b
3a-b; 4a-b
X Y
N
S
Me
Me
O
Finally, the Knoevenagel reactions between aldehydes 15,16 and
NC
acceptors, 19 and 2024 yielded the new De
peA piperidine
CN
derivatives,1e6. To the best of our knowledge, compounds 1, 3 and 5
are the first examples of 5-piperidinothiazole-based chromophores.
Concerning compounds 7e10, with a 4H-pyranylidene moiety as
a donor, their synthesis is shown in Scheme 2. Thus, the Horner
reaction of (2,6-diphenyl-4H-pyran-4-yl)diphenylphosphine oxide
(21)25 with the commercially available thiazolecarbaldehydes (22,
23) yielded the desired precursors 24 and 25, which, by lithiation
and reaction with 17a or 17b afforded the corresponding aldehydes
bearing a matched (27a,b) or a mismatched (26a,b) thiazole ring.
The Knoevenagel reaction of these aldehydes with acceptors 18 and
NC
5,6
CN
CN
X Y
S
X Y
S
O
n
O
Ph
NEt
EtN
Ph
O
Ph
Ph
O
S
19 afforded the desired DepeA compounds 7e10. To the best of our
knowledge, there is only a previous report16 in the literature on
compounds bearing a 4H-pyranylidene unit and a thiazole ring in
their structure.
7a-b; 8a-b
9,10
a: n = 0; b: n = 1
1,3,5,7,9: X=CH,Y=N; matched chromophores
2.2. X-ray diffraction: crystal structures of 4a and 6
Single crystals of 4a were grown from a CHCl3 solution at room
temperature (Fig. 1).
2,4,6,8,10: X=N,Y=CH; mismatched chromophores
1a-b; 2a-b
Me
Me
Me
CN
CN
CN
CN
CN
18
EtOH
1) n-BuLi, -78oC
Piperidine
(X=N, Y=CH)
O
2)
Me2N
17a-b
20
CHO
n
X Y
X Y
S
X Y
S
py/AcOH
Br
11,12
N
CHO
S
N
5,6
n
EtOH
(n = 0)
THF
13,14
15a-b; 16a-b
O
O
(X=CH, Y=N)
Piperidine
NEt
EtOH
S
NEt
19
Cl
Ni-Pr
i-PrN
(4 mol %)
3a-b; 4a-b
t-BuONa, DME, 80ºC
a: n = 0; b: n = 1
Rh(cod)2BF4 (2 mol%)
11,13,15: X=CH,Y=N
12,14,16: X=N,Y=CH
Scheme 1. Synthesis of chromophores 1e6.

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E. Galan et al. / Tetrahedron 68 (2012) 6427e6437
6429
7a-b; 8a-b
EtOH (Piperidine)
18
1) n-BuLi, -78oC
2)
X Y
S
X Y
S
X Y
S
1) n-BuLi, -78oC
O
H P
OHC
Ph
Ph
CHO
2)
17a-b
n
22,23
THF
THF
Ph
O Ph
24, 25
Ph
O
21
Ph
Ph
O
26a-b; 27a-b
Ph
EtOH
(n = 0)
a: n = 0; b: n = 1
23,25,27: X=CH,Y=N
22,24,26: X=N,Y=CH
19
9,10
Scheme 2. Synthesis of chromophores 7e10.
ꢁ
Moreover, the fact that the C8eC9 bond is shorter (1.390 A) than
H7
C7
C8
the corresponding bond in a related compound with a phenyl ring
O2
27
ꢁ
N2
C6
instead of thiazole (1.430 A), is consistent with the increase in
electronic delocalization when using five-membered hetero-
aromatic rings instead of phenyl.2a,b,3,7a,8,47 As an additional con-
firmation for the ICT, the difference between the C8eC9 and the
C9
C5
C10
N1
ꢁ
C9]C10 bond lengths is 0.014 A, and although 4a contains only
a single methine unit, this value can be approximated as the bond
length alternation (BLA) along the spacer (defined as the difference
between the average carbonecarbon single and double bond
C1
lengths).30 Given that for cyanines BLA w0 A, 4a is close to the
ꢁ
cyanine limit in the solid state.
Single crystals of compound 6 were obtained by slow diffusion
of hexane into a concentrated solution of the chromophore in
CH2Cl2/CHCl3 at room temperature. Compound 6 crystallizes in the
monoclinic space group P21/n, and some of the main features of its
Fig. 1. Molecular structure of 4a.
Compound 4a crystallizes in the triclinic space group Pꢀ1. The
neighbouring chromophores are linked by nonclassical
C7eH7/O2 hydrogen bonding interaction (geometric parameters
ꢁ
structure are similar to those of 4a. The BLA value for 6 is 0.050 A,
a
close to the optimal one.31 A complete description of the crystal
structure is reported in the Supplementary data.
ꢁ
ꢁ
for intermolecular contact: DeH 0.93 A, H/A 2.37 A, D/A
ꢁ
ꢁ
3.216(4) A, DeH/A 151.8 ; symmetry code: 1ꢀx, 1ꢀy, 1ꢀz; see
Fig. S69, in Supplementary data), that has already been found in
other thiazole systems.26
2.3. 1H NMR studies
The
p
-system is essentially planar, as expected for highly con-
The structures of the chromophores were analyzed by 1H NMR
spectroscopy. This technique affords valuable information about
both the geometry and the ground-state polarization of the studied
molecules. Concerning the stereochemistry, 3JHH coupling constant
analysis of the polyenic derivatives (1be4b, 7b, 8b) and 5, 6 in-
jugated structures. In fact, the angle between the mean planes of
the thiazole and the acceptor rings is 1.8ꢁ. There is evidence for
opening out of the bond angle in the methine bridge to accom-
modate the planar structure, with the angle C10eC9eC8 of 135.5ꢁ
being particularly large for a trigonal centre (bigger distortions
have been found for related compounds containing a phenyl ring
instead of the thiazole unit).27
Moreover, it can be seen that the thiazole-exocyclic C8eC9 bond
has an s-trans conformation, like that found in related 2-
aminothiazole-5-carbaldehydes.28
Bond lengths reveal intramolecular charge transfer from the
donor to the acceptor. Thus, N1eC6 and N2eC7 bonds are shorter
than the corresponding bonds in 2-aminothiazole derivatives
lacking a powerful electron-withdrawing group in 5-,29 whereas an
accompanying lengthening of the N2eC6 and C7eC8 bonds in 4a is
also observed. An additional evidence of the charge delocalization
along the chromophore is the sp2 hybridization of the piperidine
nitrogen (geometrical angles of 122.6ꢁ for C5eN1eC6, 122.5ꢁ for
C1eN1eC6 and 114.7ꢁ for C1eN1eC5).
3
dicates an all-trans geometry along the spacer, with JHH values
ranging from 14.1 Hz to 15.8 Hz for the eCH]CHe bonds and from
10.8 to 12.5 Hz for the ]CHeCH]bonds (compound 1b was
obtained as an E/Z mixture (80:20)). Selective ge-1D NOESY ex-
periments were carried out in order to determine the conforma-
tions adopted in solution by our DethiazoleeA systems (see
discussion in Supplementary data).
1H NMR data also provide valuable information about the
ground-state polarization of the studied chromophores, through
3
the use of JHH and
DJ values, since DJ, defined as the difference
3
between the averaged JHH values of the double and single bonds
along the polymethine chain32 ranges from 0 Hz in cyanines to ca.
6 Hz in polyenes.33 Comparison of the 3JHH values of compounds 1b
and 2b (Fig. 2), reveals that the presence of a matched thiazole gives
rise to a less polarized/more alternated structure than that of

ꢀ
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E. Galan et al. / Tetrahedron 68 (2012) 6427e6437
Table 1
7.30
7.28
Electrochemicala and UVevis data
N
S
N
S
H2
H1
H3
H1
H3
b
lmaxb (CH2Cl2) (log
3 )
lmax (DMF) (log
3 )
N
N
Compd
Eox
Ered
1a
2a
1b
2b
3a
4a
3b
4b
5
þ1.25
þ1.44c
þ0.95
þ1.15
þ1.13
þ1.31
þ0.92
þ1.06
þ0.97
þ1.17e
þ0.90
þ0.90
þ0.74
þ0.81
þ0.80
þ0.85
ꢀ1.12
ꢀ1.36
ꢀ0.97
ꢀ1.12
ꢀ1.00
ꢀ1.16
ꢀ0.75
ꢀ0.90
ꢀ0.68
ꢀ0.83
ꢀ0. 87
ꢀ1.01
ꢀ0.80
ꢀ0.94
ꢀ0.71
ꢀ0.83
481 (4.82)
428 (4.69)
529 (4.48)
488 (4.66)
506 (sh), 534 (4.89)
486 (4.94)
611 (4.73)
564 (4.94)
617 (4.49)
535 (4.80), 568 (4.86)
603 (4.66)
546 (4.73), 576 (sh)
614 (4.58)
569 (4.72)
672 (4.69)
488 (4.67)
428 (4.69)
536 (4.52)
487 (4.65)
H2
7.45
7.50
6.44
6.90
NC CN
NC CN
511 (sh), 538 (4.85)
487 (4.98)
2b
1b
629d
516 (sh), 568 (4.95)
642 (4.66)
532 (sh), 569 (4.80)
592 (4.56)
544 (4.70)
600 (4.59)
559 (4.74)
633 (4.49)
608 (4.55)
J : 14.8 Hz
J : 11.9 Hz
ΔJ: 2.9 Hz
J : 14.3 Hz
J : 11.8 Hz
ΔJ: 2.5 Hz
12
12
6
23
23
7a
8a
7b
8b
9
3
Fig. 2.
d
(ppm), JHH and
D
J values (in CD2Cl2) for compounds 1b ((E)-isomer) and 2b.
10
584 (sh), 618 (4.64)
a
In volts, 10ꢀ3 M in CH2Cl2 versus Ag/AgCl (KCl 3 M), glassy carbon working
electrode, Pt counter electrode, 20 ꢁC, 0.1 M Bu4NPF6 100 mV sꢀ1 scan rate. Ferro-
cene internal reference E1/2¼þ0.46 V.
a mismatched analogue as judged by the higher DJ values shown by
the former. This trend in J values is in agreement with that found in
other thiazole regioisomers recently studied.10 Furthermore, the
chemical shifts of the H atoms along the spacer (Fig. 2) show the
typical oscillatory behaviour33a,34 of a merocyanine-like chromo-
phore. The increased shielding of H2 in 2b when compared to 1b,
b
In nm.
1=2
c
E
ox
(
DEp¼0.16 V).
d
e
3
cannot be determined due to its decomposition.
1=2
E
(
DEp¼0.15 V).
ox
also points to an increased electron density on the
bridge in 2b, and consequently to a more polarized structure.
J values for 3b (2.3 Hz) and 4b (1.6 Hz) also reveal less alter-
p-conjugated
2.5. UVevis spectroscopy
D
nated structures for thiobarbiturates than for the dicyano-
methylene derivatives, according to the higher acceptor ability of
the former. When different donors are compared, the pyranylidene
All compounds show strong intramolecular charge transfer
transitions in the visible region (Table 1) (see spectra in
Supplementary data). For systems 1e4, lmax values increase on
lengthening the spacer showing vinylene shifts between 50 and
80 nm (both in CH2Cl2 and DMF) pointing to weakly alternated
structures, whereas for 7e8, the increase in lmax values is re-
markably low (around 10e20 nm), possibly due to their less po-
larized structures, as disclosed by 1H NMR data.
derivatives show higher
DJ values (DJ for 7b: 3.9 Hz; DJ for 8b:
2.8 Hz), than the piperidino analogues, thus suggesting a lower ICT
for the pyranylidene-containing chromophores. The shift of the
polyenic spacer protons of 7b, 8b to lower fields respect to 1b, 2b
confirms this feature.
The proaromatic character of the pyranylidene donor has been
previously established,16,35 and it is known that the protons of the
pyranylidene ring undergo downfield shifts as the pyrylium char-
acter of the ring increases.36 For the herein reported compounds
(Table S1, Supplementary data), the chemical shifts of the pyr-
anylidene ring protons increase on shortening the polyenic spacer,
thus demonstrating that the contribution of the aromatic pyrylium
form is higher for the shorter derivatives, in agreement with other
lmax values also allow a broad comparison of the electron-
withdrawing abilities of the different acceptor groups
(TCF>thiobarbiturate>dicyanomethylene).
The orientation of thiazole has a significant effect on the elec-
tronic absorption properties of the chromophores.9e11,18 Thus, the
presence of a matched thiazole causes a significant red shift of lmax
(e.g., 48 nm for 3a/4a and 57 nm for 7a/8a, both in CH2Cl2), in
agreement with the electrochemical measurements.
DepeA systems with a 4H-pyran-4-ylidene unit previously
In general, larger molar extinction coefficients
3
are found for
described.35
the mismatched derivatives, contrary to the few experimental ex-
amples of matched/mismatched pairs reported in the literature.9e11
This trend parallels that of the calculated oscillator strengths f
2.4. Electrochemistry
reported for other thiazole Dep
eA compounds.37,38
Most of the compounds show an almost negligible sol-
vatochromism from CH2Cl2 to DMF (Dl values ranging from ꢀ14 to
7 nm, except for 5 that shows Dl¼25 nm and 9, Dl¼ꢀ39 nm; on the
energy scale these shifts range from þ0.05 to ꢀ0.04 eV and values
for 5 and 9 are ꢀ0.08 eV and þ0.11 eV, respectively), thus sug-
gesting a cyanine-like character for these compounds. For instance,
the Dl value of compound 4a (1 nm) is in line with its very low BLA
value obtained from X-ray data, indicating that its structure is close
to cyanine limit both in the solid state and in solution. It is in-
teresting to note that when comparing dioxane and CH2Cl2, com-
pounds 7e8 exhibit positive solvatochromism (lmax (nm) in
dioxane: 7a: 544; 7b: 586; 8a: 530; 8b: 550). This variety of sol-
The redox properties of compounds 1e10 were investigated by
cyclic voltammetry (CV) (Table 1). All the NLO chromophores show
irreversible redox processes except for 2a and 6, that exhibit re-
versible oxidationereduction properties in positive scans.
For compounds 1e4 and 7e8, lengthening the spacer gives rise
to a decrease of Eox and jEredj values, thus pointing to a decrease in
the interaction between the donor and acceptor end groups.
Moreover, for a given donor and spacer length, when changing
the acceptor from dicyanomethylene to the thiobarbiturate group
there is a shift of the jEredj values towards less cathodic potentials,
pointing to the superior acceptor ability of the thiobarbiturate
group when compared to dicyanomethylene. 1H NMR and UVevis
also support the comparatively weaker electron-withdrawing ef-
fect of the dicyanomethylene group. On the other hand, there is
a shift of the Eox values towards less anodic potentials when passing
from dicyanomethylene to thiobarbiturate derivatives.
vatochromic behaviour has already been reported for other DepeA
systems,39 including thiazole derivatives.10
2.6. Calculated structures
In comparison, all the matched thiazole-based NLO chromo-
phores exhibit lower reduction/oxidation potentials than their
mismatched isomers, in agreement with previous results.9e11
In order to gain insight into the ground-state electronic struc-
tures of the studied chromophores their gas phase structures were

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E. Galan et al. / Tetrahedron 68 (2012) 6427e6437
6431
calculated using the HartreeeFock (HF) model. Given the number of
2.7. Nonlinear optical properties
possible conformational isomers, and in order to simplify the fol-
lowing discussion, we have chosen for pushepull systems 1e10 the
geometries shown in Fig. 3, and from now on, calculated data used in
the text will refer tothese conformations, which may not necessarily
represent the lowest-energy conformation of each chromophore,
but mimic the ones observed by X-ray studies for 4a and 6.
The second-order nonlinear optical properties of compounds
1e9 were measured by electric field-induced second harmonic
generation (EFISH) in CH2Cl2 at 1907 nm (Table 3). The corre-
sponding static (zero-frequency) mb0 values determined using the
two-level model40 are also gathered in Table 3 (for the sake of
X Y
S
X Y
S
X Y
S
N
N
Me
Me
O
H
H
nA
n A
Ph
O
Ph
NC
CN
NC
(c)
(b)
(a)
O
NEt
X=CH,Y=N; matched chromophores
X=N,Y=CH; mismatched chromophores
CN
CN
A =
S
NEt
O
Fig. 3. Geometries used for the calculations: (a) for 1e4; (b) for 5e6; (c) for 7e10.
Calculated BLA values (along the acyclic spacer connecting the
thiazole moiety to the acceptor group) on gas phase HF/6-31G*
geometries for compounds 1b, 2b, 3a, 4a, 5, 6 (chosen as model
compounds) are collected in Table 2.
comparison, Disperse Red 1, a common benchmark for organic NLO
chromophores, gives a mb0 value of w480ꢂ10ꢀ48 esu in the same
experimental conditions).
As it has been previously observed for other NLO-chromophores
studied, thiobarbituric derivatives (3b, 4b, 9) show mb values higher
than those of their dicyanomethylene analogues (1b, 2b, 7a) (the
comparison between 1ae2a and 3ae4a, respectively constitutes an
exception). Moreover, comparison of compounds a and b reveals
that lengthening the polyenic chain by a single vinylene unit gives
rise to an important increase in the NLO responses.
Table 2
Calculated BLA values along the spacer for selected compounds
ꢁ
ꢁ
Compd
BLA (A)
Compd
BLA (A)
1b
3a
3b
5
0.111
0.080
0.101
0.116
2b
4a
4b
6
0.093
0.046
0.082
0.095
Regarding the influence of a matched/mismatched thiazole on
the NLO propertiesof the studied chromophores (Fig. 5; red bars), the
largest experimental difference between a matched/mismatched
pair is found for compounds 1a/2a (factor of 1.8), whereas for com-
pounds 3e4, this value is close to 1.35 and for the rest of the mea-
sured systems, there is an almost negligible difference between the
mb0 valuesof thematched andthemismatched derivatives. Therefore
the experimental results do not conform with the previous
theoretically-derived trends.2c,3,5,6 In fact, the reported experimental
increase in the NLO properties when passing from a mismatched
Inspection of data reveals that BLA is reduced in the chromo-
phores with mismatched thiazoles compared to that of the corre-
sponding matched species. This is consistent with the results
obtained for other thiazole Dep
eA systems10,37 and with our NMR
studies, showing that the introduction of a matched thiazole results
in a more alternated structure.
Moreover, when dicyanomethylene and thiobarbiturate de-
rivatives are compared, BLA values decrease in the order 1b, 2b>3b,
4b, suggesting that the thiobarbiturate group is a stronger acceptor,
in agreement with NMR and UVevis data and CV measurements.
Dep
eA derivative to a matched analogue9,10,18 is not that consider-
able, since the values of the experimental ratio (b0 matched/b0
mismatched) are around 1.1e1.2, in agreement with our own data.
In order to gain a deeper understanding of the structure-
properties relationship in our chromophores, mb0 values were
also calculated theoretically. Although it has been reported that
most Quantum-chemistry methods predict successfully trends in
hyperpolarizabilities,41 DFT methods often give rise to highly
overestimated values.42 Therefore we have chosen the coupled
perturbed HartreeeFock (CPHF) method with the aim to obtain
Besides, it can be seen that on lengthening the
p-spacer BLA in-
creases (3a, 4a<3b, 4b) confirming that longer derivatives (3b, 4b)
are less polarized.
Finally, as exemplified by pyranylidene derivatives 7a, 8a, 9, 10
Mulliken charges (Fig. 4) show that the negative charge is con-
centrated on the acceptor,11,12,15,16 and the positive charge is spread
over the donor and the
p-spacer, whereas the thiazole moiety re-
more reliable calculated
using the HF/6-31G* model chemistry on the geometries described
in Section 2.6. These values, together with the calculated ground-
b values. The calculations were performed
mains almost neutral. Moreover, the mismatched derivatives are
more polarized than their matched analogues, thus confirming the
1H NMR and BLA results.
state dipole moments (m) are collected in Table 3.
For piperidine derivatives 1e6, the same trends are observed
(see Fig. S74 in Supplementary data), although more negative
charges are concentrated on the acceptor end of these compounds
(e.g., 1a: ꢀ0.30/7a: ꢀ0.27; 3a: ꢀ0.35/9: ꢀ0.30); this higher degree
of polarization for the piperidine derivatives is in agreement with
1H NMR results and UVevis data.
The calculated mb0 values show essentially the same trends that
the experimental results in terms of the effects of the acceptor and
the length of the polyenic chain.
Concerning the influence of a matched/mismatched thiazole on
the calculated NLO properties (Fig. 5; blue bars), it should be noted

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E. Galan et al. / Tetrahedron 68 (2012) 6427e6437
6432
Compd
D
Th
S
A
Th
π-Spacer
7a
8a
9
+0.14
+0.19
+0.13
+0.18
−0.07
−0.05
−0.03
+0.01
+0.20
+0.20
+0.20
+0.19
−0.27
−0.34
−0.30
−0.38
(S)
Acceptor
Donor
(D)
10
Fig. 4. Mulliken atomic charges on various molecular domains for compounds 7a, 8a, 9, 10.
optimized geometries reproduce quite well the experimental re-
sults, with a very close parallelism, being compounds 3a/4a an
exception.
Table 3
Experimental and CPHF-calculateda NLO properties
Compd
Experimental
Calculated
Thus, when a considerable number of pairs of matched/mis-
matched chromophores have been studied it can be seen that
previous theoretical studies carried out on semiempirical2c,3 or
B3LYP geometries,5 with semiempirical3 (ZINDO) or Density
Functional Theory (DFT) methods2c,5 (B3LYP, LDA, PW86P86 func-
tionals) for b0 calculations do not reproduce the experimental re-
sults. Matched chromophores do not always show markedly higher
second-NLO responses than its mismatched isomers. Nevertheless,
our theoretical CPHF calculations carried out on HF geometries
parallel the experimental data.
Taking all data into account, our experimental and calculated re-
sults show that the role played by the orientation of the thiazole ring
is less relevant than the character of the end groups for tuning the
second-order NLO responses of DethiazoleeA compounds.5 More-
over, this behaviour is also observed in other DethiazoleeA com-
pounds where the donor and the thiazole spacer are not directly
linked, but connected through aromatic rings, as demonstrated by
their low experimental b0 matched/b0 mismatched ratio(ca.1.1).9,10,18
mbb,c
mb0
mb0
me,f
9.78
c,d
c,e
1a
2a
1b
2b
3a
4a
3b
4b
5
300
160
780
620
200
140
210
120
500
430
125
95
303
169
488
452
367
158
662
526
920
837
399
262
522
447
445
287
9.78
9.76
10.52
8.73
8.86
8.84
9.28
17.20
16.34
8.11
8.06
8.16
8.42
6.48
6.88
1220
780
640
460
730
765
650
620
1150
1170
1400
1300
1200
1000
2200
1990
6
7a
8a
7b
8b
9
2000
880
g
g
10
a
Calculations using the HF/6-31G* model for the structures shown in Fig. 3.
mb values determined in CH2Cl2 at 1907 nm; experimental accuracy: ꢃ15%,
b
except for 7a,9 (ꢃ20%).
c
In 10ꢀ48 esu.
d
Experimental mb0 values calculated using the two-level model.
CPHF/6-31G* on HF/6-31G* geometries optimized.
In Debye.
3. Conclusions
e
f
The influence of thiazole regioisomerism on second-order NLO
properties has been experimentally studied by synthesizing and
comparing the NLO responses of eight new pairs of analogous
matched/mismatched DethiazoleeA systems.
Mismatched derivatives show more polarized structures than
their matched analogues, as shown by 1H NMR spectra, calculated
BLA values and Mulliken charges. On the other hand, CV and UVevis
spectra show lower gaps for the matched chromophores.
g
Not determined due to its low solubility.
that most of the mb0 enhancement on passing from the mismatched
to the matched systems is due to the hyperpolarizability contri-
bution, since the change in
can be seen in Fig. 5 our calculated mb0 values based on HF
m
values is comparatively small.43 As it
Whereas previous theoretical results show that the matched de-
rivatives have much higher calculated mb0 values than their mis-
matched analogues, experimental NLO measurements of regioisomers
1e10 show that, in general, there are only small differences between
the NLO responses of the matched and the mismatched derivatives.
Our theoretical CPHF calculations parallel this trend.
This indicates that the influence of the orientation of the thiazole
ring in DethiazoleeA compounds on second-order NLO properties
has been overestimated by previous theoretical calculations and
that this orientation is less relevant than the character of the donor
and acceptor groups for tuning the second-order nonlinearities.
4. Experimental
4.1. General experimental methods
Compounds 11, 12, 17a,b, 18, 19, 22 and 23 are commercially
available and were used without further purification. THF was
Fig. 5. Experimental ( ) and CPHF-calculated (
ratio.
) mb0 (matched)/mb0 (mismatched)

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E. Galan et al. / Tetrahedron 68 (2012) 6427e6437
6433
refluxed with sodium and benzophenone and freshly distilled prior
to use.
The molecular mb values have been determined in dichloro-
methane for all compounds. As a rule, three solutions of concen-
tration in the range (5ꢂ10ꢀ3Me4ꢂ10ꢀ4 M) were measured. mb0
values were extrapolated using a two-level dispersion model.40a
Under the same experimental conditions mb0 deduced for DR1
was 480ꢂ10ꢀ48 esu, quite close to the value reported in the same
solvent by Dirk et al.47
Infrared measurements were carried out in Nujol mulls using
a PerkineElmer FTIR 1600 spectrometer. Melting points were
obtained on a Gallenkamp apparatus and are uncorrected. Ele-
mental analysis was performed with a PerkineElmer 240C micro-
analyzer. 1H and 13C NMR spectra were recorded on a Bruker
ARX300 or a Bruker AV400 at 300 or 400 MHz and 75 or 100 MHz,
respectively;
d
values are given in parts per million (relative toTMS)
4.4. Computational procedures
and J values in hertz. 1He1H COSY experiments were recorded at
400 MHz in order to establish peaks assignment and spatial re-
lationships. Selective ge-1D NOESY experiments (mixing time:
1.1e3.7 s; selective 180 pulse: 20e40 ms) were recorded at
300 MHz for compounds 5, 6, 7a, 8a, in order to determine the
conformations adopted in solution. Electrospray mass spectra were
recorded on a Bruker Q-ToF spectrometer; accurate mass mea-
surements were achieved using sodium formate as external refer-
ence. Electronic spectra were recorded with a UVevis UNICAM UV4
spectrophotometer. Cyclic voltammetry measurements were per-
All theoretical calculations were performed by using the
Gaussian 0948 program. The molecular geometries were optimized
using the HF functional and the 6-31G*49 basis set. Molecular
hyperpolarizabilities at zero frequency were calculated by the
Coupled Perturbed HartreeeFock method (CPHF).
4.5. Synthesis and characterization
Compounds 14,20 16a,19,21 2024 and 2125 were prepared as
formed with a
m-Autolab ECO-Chemie potentiostat, using a glassy
previously described.
carbon working electrode, Pt counter electrode, and Ag/AgCl ref-
erence electrode. The experiments were carried out under argon, in
CH2Cl2, with Bu4NPF6 as supporting electrolyte (0.1 mol Lꢀ1); scan
4.5.1. 5-(Piperidin-1-yl)thiazole (13). 5-Bromothiazole (1.55 g,
9.0 mmol), piperidine (2.7 mL, 27.0 mmol), sodium tert-butoxide
(1.78 g, 18.0 mmol), Rh(cod)2BF4 (73 mg, 2.0 mol %), 1,3-
diisopropylimidazolium chloride (70 mg, 4.0 mol %) and 1,2-
dimethoxyethane (9 mL) were mixed under argon atmosphere.
The reaction mixture was vigorously stirred at 80 ꢁC overnight,
then it was cooled down to room temperature and diluted with
AcOEt. The crude reaction was filtered through a pad of silica gel,
the organic solvents were evaporated and the residue was purified
by flash chromatography on silica gel using as eluent CH2Cl2/AcOEt
10:0.5, then 10:1, to afford a slightly yellow oil (1.40 g; 92%). Found:
C 57.49, H 6.92, N 16.48. C8H12N2S requires C 57.11, H 7.19, N 16.65%.
IR (Nujol, cmꢀ1): 1651 (C]N), 1558 (C]C), 1539 (C]C). 1H NMR
can rate was 100 mV sꢀ1
.
4.2. X-ray diffraction
X-ray data collection were carried out on an Xcalibur, Sapphire 3
diffractometer equipped with a graphite monochromator (Mo K
a
ꢁ
radiation,
l¼0.71073 A). The diffraction frames were integrated and
corrected for absorption using the CrysAlis RED package.44 The
structures were solved by direct methods.45 All refinements were
carried out using SHELXL-9746 against the F2 data using full-matrix
least squares methods. All non-hydrogen atoms were refined with
anisotropic displacement parameters. All hydrogen atoms were
placed at idealized positions and assigned isotropic displacement
parameters 1.2 times the Uiso value of the corresponding bonding
partner (1.5 times for methyl hydrogen atoms).
(400 MHz, CDCl3):
d 8.16 (s, 1H), 7.01 (s, 1H), 3.15e3.05 (m, 4H),
1.75e1.68 (m, 4H), 1.60e1.53 (m, 2H). 13C NMR (75 MHz, CDCl3):
d
156.0, 140.5, 122.3, 53.5, 25.1, 23.5. HRMS (ESIþ): found 169.0789
[MþH]þ. C8H13N2S requires 169.0794.
A complete description of the crystal structures is reported in
the Supplementary data.
4.5.2. Compounds 15a,b and 16b. General procedure. A solution of
the corresponding (piperidin-1-yl)thiazole 13, 14 (353 mg,
2.1 mmol) in anhydrous THF (15 mL) was cooled down to ꢀ78 ꢁC
under argon atmosphere, and n-BuLi (1.6 M in hexanes, 1.6 mL,
2.5 mmol) was added dropwise. After stirring for 1 h, DMF (17a) (for
15a) or (E)-3-dimethylaminoacrylaldehyde (17b) (for 15b, 16b)
(3.2 mmol) was added dropwise and the reaction medium was
slowly warmed to 0 ꢁC. Water (10 mL) was added for quenching the
reaction, and the aqueous layer was then extracted with AcOEt
(3ꢂ10 mL). The organic layer was washed with H2O (10 mL) and
dried over MgSO4. Solvent was evaporated.
Crystallographic data (excluding structure factors) for the
structures in this paper have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication No.
CCDC 875491 (4a) and 875490 (6). Copies of the data can be
obtained, free of charge, on application to CDCC, 12 Union Road,
Cambridge CB2 1EZ, UK (e-mail: deposit@ccdc.cam.ac.uk).
4.3. NLO measurements
Electric field-induced second harmonic generation (EFISH)
measurements have been performed using as the fundamental
radiation the 1.9
mm output of a H2 Raman shifter pumped by a Q-
4.5.2.1. 5-(Piperidin-1-yl)thiazol-2-carbaldehyde
(15a). The
switched Nd/YAG laser. This laser operates at 1064 nm, with
a repetition rate of 10 Hz and pulse width of 8 ns. A computer
controlled NLO spectrometer completes the SHG experimental set-
product was used without further purification. Yield: brown oil
(387 mg; 94%). Found: C 54.78, H 5.98, N 14.51. C9H12N2OS requires
C 55.08, H 6.16, N 14.27%. IR (Nujol, cmꢀ1): 1653 (C]O), 1507 (C]
up. The 1.9
mm incident light is split in two beams. The less intense
C). 1H NMR (300 MHz, CDCl3):
d 9.64 (s, 1H), 7.15 (s, 1H), 3.35e3.28
one is directed to a N-(4-nitrophenyl)-(
L)-prolinol (NPP) powder
(m, 4H), 1.75e1.57 (m, 6H). 13C NMR (75 MHz, CDCl3):
d 182.3, 163.0,
sample whose SH signal is used as a reference in order to reduce the
effects of laser fluctuations. The other beam is passed through
a linear polarizer and focused into the EFISH wedge shaped liquid
148.6, 123.7, 51.9, 24.7, 23.2. HRMS (ESIþ): found 219.0571
[MþNa]þ. C9H12N2NaOS requires 219.0563.
cell. Voltage pulses of 5 kV and 3
ms are applied across the cell
4.5.2.2. (E)-3-(5-(Piperidin-1-yl)thiazol-2-yl)acrylaldehyde
(2 mm gap between the electrodes) synchronously with the laser
pulses. The harmonic signals from both the EFISH cell and the NPP
reference are measured with two photomultipliers. Interference
filters are used to remove the residual excitation light beyond the
sample and the reference.
(15b). The product was dissolved in ether and cooled down to
0
Yield: brown solid (135 mg; 29%). Found: C 59.70, H 6.58, N
12.49. C11H14N2OS requires C 59.43, H 6.35, N 12.60%. Mp
95e106 ꢁC. IR (Nujol, cmꢀ1): 1663 (C]O), 1603 (C]N), 1508 (C]
ꢁC. The precipitate was filtered and washed with cold ether.

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E. Galan et al. / Tetrahedron 68 (2012) 6427e6437
6434
C). 1H NMR (300 MHz, CDCl3):
d
9.62 (d, J¼7.7 Hz, 1H), 7.47 (d,
245.0855; found 267.0658 [MþNa]þ. C12H12N4NaS requires
J¼15.7 Hz, 1H), 7.07 (s, 1H), 6.43 (dd, J¼15.7 Hz, J0¼7.7 Hz, 1H),
267.0675.
3.30e3.25 (m, 4H), 1.78e1.70 (m, 4H), 1.69e1.60 (m, 2H). 13C NMR
(75 MHz, CD2Cl2):
d
192.5, 159.9, 146.7, 144.7, 126.3, 123.3, 52.5,
4.5.3.4. (E)-2-(3-(2-(Piperidin-1-yl)thiazol-5-yl)allylidene)malo-
24.9, 23.4. HRMS (ESIþ): found 223.0891 [MþH]þ. C11H15N2OS
requires 223.0900; found 245.0703 [MþNa]þ. C11H14N2NaOS re-
quires 245.0719.
nonitrile (2b). Reaction time: 4 h. Yield: red solid (70 mg; 78%).
Found: C 62.43, H 4.95, N 20.89. C14H14N4S requires C 62.20, H 5.22,
N 20.72. Mp 177e182 ꢁC. IR (Nujol, cmꢀ1): 2221 (C^N), 1599 (C]
N), 1584 (C]C), 1543 (C]C). 1H NMR (300 MHz, CD2Cl2):
d 7.54 (s,
4.5.2.3. (E)-3-(2-(Piperidin-1-yl)thiazol-5-yl)acrylaldehyde
(16b). The product was purified by flash chromatography (silica
gel) using as eluent first hexane/AcOEt (1:1), then hexane/AcOEt
(3:4). Yield: brown solid (248 mg; 53%). Found: C 59.10, H 6.11, N
1H), 7.45 (d, J¼11.8 Hz, 1H), 7.30 (d, J¼14.3 Hz, 1H), 6.44 (dd,
J¼14.3 Hz, J0¼11.8 Hz, 1H), 3.68e3.57 (m, 4H), 1.77e1.65 (m, 6H). 13C
NMR (75 MHz, CD2Cl2):
d 174.5, 160.0, 152.6, 141.3, 124.7, 117.9,
115.5, 113.5, 76.0, 50.5, 25.7, 24.4. HRMS (ESIþ): found 271.1012
[MþH]þ. C14H15N4S requires 271.1012; found 293.0819 [MþNa]þ.
C14H14N4NaS requires 293.0831.
12.86. C11H14N2OS requires
C 59.43, H 6.35, N 12.60%. Mp
107e109 ꢁC. IR (Nujol, cmꢀ1): 1650 (C]O), 1601 (C]N). 1H NMR
(300 MHz, CD2Cl2):
d
9.39 (d, J¼7.8 Hz, 1H), 6.00 (dd, J¼15.0 Hz,
J0¼7.8 Hz, 1H), 7.38 (d, J¼15.0 Hz, 1H), 7.37 (s, 1H), 3.52e3.44 (m,
4.5.4. 1,3-Diethyl-5-((5-(piperidin-1-yl)thiazol-2-yl)methylene)-2-
4H), 1.63e1.55 (m, 6H). 13C NMR (75 MHz, CD2Cl2):
d
192.5, 173.8,
thioxo-dihydropyrimidine-4,6-dione
(3a). 5-(Piperidin-1-yl)thia-
149.0, 143.3, 124.4, 123.6, 50.2, 25.7, 24.5. HRMS (ESIþ): found
223.0896 [MþH]þ. C11H15N2OS requires 223.0900; found 245.0718
[MþNa]þ. C11H14N2NaOS requires 245.0719.
zole-2-carbaldehyde (15a) (49 mg, 0.25 mmol) and 1,3-diethyl-2-
thiobarbituric acid (19) (48 mg, 0.24 mmol) were dissolved in
EtOH (5 mL) under argon atmosphere. The reaction mixture was
stirred for 90 min at room temperature and then it was cooled
down to 0 ꢁC. The resulting precipitate was filtered and washed
with cold EtOH. The solid was dissolved in AcOEt, washed first with
a saturated solution of K2CO3 (2ꢂ2 mL) and then with water (2 mL).
The organic layer was dried over MgSO4, and the solvent evapo-
rated to afford a pink pure solid (11 mg; 11%). Found: C53.68, H
5.65, N 14.98. C17H22N4O2S2 requires C 53.94, H 5.86, N 14.80%. Mp
190 ꢁC (dec). IR (Nujol, cmꢀ1): 1645 (C]O). 1H NMR (300 MHz,
4.5.3. Compounds 1a,b and 2a,b. General procedure. The corre-
sponding aldehyde (15a,b, 16a,b) (0.33 mmol) and malononitrile
(18) (26 mg, 0.40 mmol) were dissolved in EtOH (8 mL) under argon
atmosphere (for 2a, piperidine (1 drop) was added additionally)
and the reaction mixture was refluxed during 1e4 h (TLC moni-
toring). Then, it was cooled down to 0 ꢁC and after the addition of
hexane, the resulting precipitate was filtered and washed with cold
hexane. For compound 1b a further purification by recrystallization
from CH2Cl2/isopropyl alcohol was needed.
CDCl3):
d 8.67 (s, 1H), 7.66 (s, 1H), 4.65e4.52 (m, 4H), 3.66e3.56 (m,
4H), 1.86e1.70 (m, 6H), 1.38e1.25 (m, 6H). 13C NMR (75 MHz,
CDCl3):
d 178.5, 168.2, 161.1, 160.5, 148.4, 142.2, 130.3, 105.1, 52.3,
4.5.3.1. 2-((5-(Piperidin-1-yl)thiazol-2-yl)methylene)malononi-
trile (1a). Reaction time: 1 h 30 min. Yield: orange solid (45 mg;
56%). Found: C 59.08, H 4.67, N 22.99. C12H12N4S requires C 58.99, H
4.95, N 22.93%. Mp 128e129 ꢁC. IR (Nujol, cmꢀ1): 2213 (C^N), 1579
43.7, 42.8, 25.2, 23.3, 12.5, 12.3. HRMS (ESIþ): found 379.1243
[MþH]þ. C17H23N4O2S2 requires 379.1257; found 401.1063
[MþNa]þ. C17H22N4NaO2S2 requires 401.1076.
(C]C). 1H NMR (300 MHz, CD2Cl2):
d
7.69 (s, 1H), 7,34 (s, 1H),
4.5.5. (E)-1,3-Diethyl-5-(3-(5-(piperidin-1-yl)thiazol-2-yl)allyli-
dene)-2-thioxo-dihydropyrimidine-4,6-dione (3b). (E)-3-(5-(Piper-
idin-1-yl)-thiazol-2-yl)acrylaldehyde (15b) (222 mg, 1.0 mmol) and
1,3-diethyl-2-thiobarbituric acid (19) (180 mg, 0.9 mmol) were
dissolved in EtOH (3 mL) under argon atmosphere and the mixture
was stirred at room temperature for 1 h. Then it was cooled down
to 0 ꢁC and the resulting precipitate was filtered and washed with
hexane/EtOH (7:3) to afford a dark green solid (39 mg; 60%). Found:
C 56.69, H 5.85, N 13.96. C19H24N4O2S2 requires C 56.41, H 5.98, N
13.85%. Mp 179 ꢁC (dec). IR (Nujol, cmꢀ1): 1659 (C]O), 1560 (C]C).
3.53e3.45 (m, 4H), 1.82e1.65 (m, 6H). 13C NMR (75 MHz, CD2Cl2):
d
165.0, 149.9, 140.1, 126.2, 115.9, 115.2, 70.5, 53.3, 25.5, 23.8. HRMS
(ESIþ): found 245.0851 [MþH]þ. C12H13N4S requires 245.0855;
found 267.0678 [MþNa]þ. C12H12N4NaS requires 267.0675.
4.5.3.2. 2-(3-(5-(Piperidin-1-yl)thiazol-2-yl)allylidene)malononi-
trile (1b). Reaction time: 4 h. Yield: purple solid as an E/Z mixture
(80:20 ratio) (41 mg; 47%). Found: C 62.45, H 5.43, N 20.54.
C14H14N4S requires C 62.20, H 5.22, N 20.72%. Mp 139e141 ꢁC. IR
(Nujol, cmꢀ1): 2216 (C^N), 1574 (C]C), 1554 (C]C). 1H NMR
1H NMR (400 MHz, CDCl3):
d
8.29 (dd, J¼14.7 Hz, J0¼12.4 Hz, 1H),
(300 MHz, CD2Cl2):
d
9.08 (dd, J¼12.2 Hz, J0¼0.6 Hz, 1H, (Z)-isomer),
8.15 (d, J¼12.4 Hz, 1H), 7.53 (d, J¼14.7 Hz, 1H), 7.19 (s, 1H),
4.60e4.51 (m, 4H), 3.42e3.37 (m, 4H), 1.80e1.73 (m, 4H), 1.72e1.66
(m, 2H), 1.34e1.22 (m, 6H). 13C NMR was not registered due to
decomposition of the product during the experiment (CDCl3 and
CD2Cl2). HRMS (ESIþ): found 405.1412 [MþH]þ. C19H25N4O2S2 re-
quires 405.1413; found 427.1231 [MþNa]þ. C19H24N4NaO2S2 re-
quires 427.1233.
7.50 (dd, J¼11.9 Hz, J0¼0.5 Hz, 1H, (E)-isomer), 7.28 (dd, J¼14.8 Hz,
J0¼0.5 Hz, 1H, (E)-isomer), 7.18 (s, 1H, (Z)-isomer), 7.15 (s, 1H, (E)-
isomer), 6.90 (dd, J¼14.8 Hz, J0¼11.9 Hz, 1H, (E)-isomer), 6.74 (dd,
J¼11.0 Hz, J0¼0.6 Hz, 1H, (Z)-isomer), 6.46 (dd, J¼12.2 Hz, J0¼11.0 Hz,
1H, (Z)-isomer), 3.39e3.27 (m, 8H, (E)þ(Z)-isomers), 1.79e1.61 (m,
12H, (E)þ(Z)-isomers). 13C NMR (75 MHz, CD2Cl2):
d 161.9, 159.2,
158.1, 145.8, 142.2, 134.6, 125.6, 125.3, 120.0, 119.1, 115.1, 113.1, 78.7,
52.9, 25.4, 23.8. HRMS (ESIþ): found 271.1011 [MþH]þ. C14H15N4S
requires 271.1012; found 293.0831 [MþNa]þ. C14H14N4NaS requires
293.0831.
4.5.6. Compounds
4a,b. General
procedure.
1,3-Diethyl-2-
thiobarbituric acid (19) (180 mg, 0.9 mmol) and the correspond-
ing aldehyde (16a,b) (1.0 mmol) were dissolved in EtOH (7 mL)
under argon atmosphere. The reaction mixture was refluxed for
5e30 min (TLC monitoring), then cooled down to 0 ꢁC. The
resulting precipitate was filtered and washed.
4.5.3.3. 2-((2-(Piperidin-1-yl)thiazol-5-yl)methylene)malononi-
trile (2a). Reaction time: 1 h. Yield: yellow solid (47 mg; 59%).
Found: C 58.77, H 4.73, N 23.09. C12H12N4S requires C 58.99, H 4.95,
N 22.93%. Mp 177e179 ꢁC. IR (Nujol, cmꢀ1): 2218 (C^N), 1585 (C]
4.5.6.1. 1,3-Diethyl-5-((2-(piperidin-1-yl)thiazol-5-yl)methy-
lene)-2-thioxo-dihydropyrimidine-4,6-dione (4a). Solvent used for
washing: cold EtOH. Yield: orange solid (191 mg; 56%). Found: C
54.19, H 5.58, N 14.59. C17H22N4O2S2 requires C 53.94, H 5.86, N
14.80%. Mp 240e241 ꢁC. IR (Nujol, cmꢀ1): 1647 (C]O), 1633 (C]C).
C), 1549 (C]C). 1H NMR (300 MHz, CDCl3):
d
7.75 (s, 1H), 7.60 (s,
1H), 3.78e3.64 (m, 4H), 1.80e1.68 (m, 6H). 13C NMR (75 MHz,
CDCl3): d 176.3, 157.6, 148.5, 120.6, 115.3, 114.6, 68.7, 50.4, 25.2, 23.7.
HRMS (ESIþ): found 245.0846 [MþH]þ. C12H13N4S requires

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E. Galan et al. / Tetrahedron 68 (2012) 6427e6437
6435
1H NMR (400 MHz, CDCl3):
4H), 3.90e3.66 (m, 4H), 1.78e1.72 (m, 6H), 1.34e1.27 (m, 6H). 13C
d
8.41 (s, 1H), 8.10 (s, 1H), 4.60e4.52 (m,
4.6 mmol) dissolved in anhydrous THF (5 mL) was added and the
reaction medium was slowly warmed to room temperature over-
night. A saturated solution of NH4Cl (15 mL) was added and the
mixture was stirred for 5 min. THF was evaporated and AcOEt was
added to the aqueous phase. The resulting precipitate was filtered
and washed with H2O and cold AcOEt. For compound 25 a further
purification by recrystallization from CH2Cl2/EtOH was needed.
NMR (75 MHz, CDCl3): d 180.1, 178.7, 166.0, 161.3, 160.5, 147.4, 124.1,
103.8, 43.6, 42.7, 25.4, 23.8, 12.5, 12.3. HRMS (ESIþ): found 379.1267
[MþH]þ. C17H23N4O2S2 requires 379.1257; found 401.1063
[MþNa]þ. C17H22N4NaO2S2 requires 401.1076.
4.5.6.2. (E)-1,3-Diethyl-5-(3-(2-(piperidin-1-yl)thiazol-5-yl)ally-
lidene)-2-thioxo-dihydropyrimidine-4,6-dione (4b). Solvent used for
washing: hexane. Yield: purple solid (326 mg; 81%). Found: C 56.63,
H 5.76, N 13.71. C19H24N4O2S2 requires C 56.41, H 5.98, N 13.85%. Mp
216 ꢁC (dec). IR (Nujol, cmꢀ1): 1656 (C]O). 1H NMR (400 MHz,
4.5.9.1. 2-((2,6-Diphenyl-4H-pyran-4-yliden)methyl)thiazole
(24). Yield: dark yellow solid (1.27 g; 85%). Found: C 76.74, H 4.38,
N
4.36. C21H15NOS requires
C 76.57, H 4.59, N 4.25%. Mp
148e150 ꢁC. IR (Nujol, cmꢀ1): 1651 (C]N), 1583 (C]C, Ar), 1559
CDCl3):
d
8.10 (d, J¼12.5 Hz, 1H), 7.90 (dd, J¼14.1 Hz, J0¼12.5 Hz,1H),
(C]C, Ar). 1H NMR (400 MHz, CDCl3):
d
8.23 (dd, J¼1.8 Hz,
7.62 (s, 1H), 7.51 (d, J¼14.1 Hz, 1H), 4.57e4.49 (m, 4H), 3.68e3.61
J0¼0.6 Hz, 1H), 7.92e7.89 (m, 2H), 7.82e7.78 (m, 3H), 7.52e7.40 (m,
(m, 4H), 1.76e1.68 (m, 6H), 1.32e1.25 (m, 6H). 13C NMR (100 MHz,
6H), 7.11 (d, J¼3.3 Hz, 1H), 6.49 (d, J¼1.8 Hz, J0¼0.3 Hz, 1H), 6.09 (s,
CDCl3):
d
178.7, 174.4, 161.0, 160.1, 158.3, 152.9, 146.4, 126.5, 121.9,
1H). 13C NMR (CDCl3, 75 MHz):
d 166.8, 154.3, 152.7, 143.2, 133.1,
110.4, 50.1, 43.5, 42.9, 25.2, 23.8, 12.4, 12.3. HRMS (ESIþ): found
405.1425 [MþH]þ. C19H25N4O2S2 requires 405.1413; found 427.1239
[MþNa]þ. C19H24N4NaO2S2 requires 427.1233.
133.0, 132.8, 129.6, 129.4, 128.6, 128.5, 125.2, 124.6, 115.2, 107.5,
104.7, 103.9. HRMS (ESIþ): found 330.0952 [MþH]þ. C21H16NOS
requires 330.0947.
4.5.7. (E)-2-(3-Cyano-5,5-dimethyl-4-(2-(5-(piperidin-1-yl)thiazol-
2-yl)vinyl)furan-2-ylidene)malononitrile (5). 5-(Piperidin-1-yl)thi-
azole-2-carbaldehyde (15a) (56 mg, 0.29 mmol) and acceptor TCF
(20) (57 mg, 0.29 mmol) were dissolved in EtOH (7 mL) under argon
4.5.9.2. 5-((2,6-Diphenyl-4H-pyran-4-yliden)methyl)thiazole
(25). Yield: yellow solid (983 mg; 65%). Found: C 76.69, H 4.47, N
4.47. C21H15NOS requires C 76.57, H 4.59, N 4.25%. Mp 174e178 ꢁC. IR
(Nujol, cmꢀ1): 3056 (]CH),1656 (C]C). 1H NMR (300 MHz, CDCl3):
atmosphere. A mixture of pyridine (218
m
L) and acetic acid (105
m
L)
d 8.65e8.63 (m, 1H), 7.85e7.74 (m, 5H), 7.51e7.40 (m, 6H), 6.98 (dd,
was added and the reaction mixture was stirred for 24 h (TLC
monitoring) at room temperature. Then, another portion of pyri-
dine/acetic acid was added and the reaction was stirred for 24
further hours. Then it was cooled down to 0 ꢁC and the resulting
precipitate was filtered, washed with EtOH and Et2O and finally
purified by recrystallization from CH2Cl2/hexane to afford a purple
solid (24 mg; 22%). Found: C 63.74, H 4.84, N 18.32. C20H19N5OS
requires C 63.64, H 5.07, N 18.55%. Mp 234 ꢁC (dec). IR (Nujol,
cmꢀ1): 2223 (C^N), 1567 (C]C), 1523 (C]C). 1H NMR (400 MHz,
J¼2.0 Hz, J0¼0.7 Hz, 1H), 6.45 (dd, J¼2.0 Hz, J0¼0.4 Hz, 1H), 6.10 (m,
1H). 13C NMR (100 MHz, CDCl3):
d 153.6, 151.4, 149.3, 140.7, 136.1,
133.0, 132.8, 130.2, 129.7, 129.3, 128.7, 128.6, 125.0, 124.5, 107.9,
102.8, 102.0. HRMS (ESIþ): found 330.0942 [MþH]þ. C21H16NOS
requires 330.0947.
4.5.10. Compounds 26a,b and 27a,b. General procedure. A solution
of 24 or 25 (329 mg, 1.0 mmol) in anhydrous THF (15 mL) was
cooled down to ꢀ78 ꢁC under argon atmosphere, and n-BuLi
(1.6 M in hexanes, 0.75 mL, 1.2 mmol) was added dropwise. The
mixture was stirred for 1 h. The corresponding electrophile 17a,b
(1.5 mmol) was added and stirring was continued for a further
hour at ꢀ78 ꢁC, then the reaction medium was slowly warmed to
CDCl3):
d
7.56 (d, J¼15.8 Hz, 1H), 7.24 (s, 1H), 6.69 (d, J¼15.8 Hz, 1H),
3.47e3.42 (m, 4H), 1.83e1.68 (m, 12H). 13C NMR was not registered
due to its low solubility. HRMS (ESIþ): found 378.1377 [MþH]þ.
C20H20N5OS requires 378.1383; found 400.1199 [MþNa]þ.
C20H19N5NaOS requires 400.1203.
0
ꢁC. Water (20 mL) was added for quenching the reaction and
then the crude mixture was warmed to room temperature. Hexane
was added, the resulting precipitate was filtered, washed with
cold hexane and dried. For 27b, THF was evaporated, the aqueous
layer was extracted with AcOEt (3ꢂ10 mL) and the combined or-
ganic phases were first washed with H2O (2ꢂ15 mL) and then
dried over MgSO4. Solvent was evaporated and the crude was
purified by flash chromatography on silica gel using CH2Cl2/AcOEt
(9.5:0.5) as eluent.
4.5.8. (E)-2-(3-Cyano-5,5-dimethyl-4-(2-(2-(piperidin-1-yl)thiazol-
5-yl)vinyl)furan-2-ylidene)malononitrile (6). 2-(Piperidin-1-yl)thi-
azole-5-carbaldehyde (16a) (121 mg, 0.62 mmol) and acceptor TCF
(20) (113 mg, 0.57 mmol) were dissolved in EtOH (10 mL) under
argon atmosphere. A mixture of pyridine (436
mL) and acetic acid
(210 L) was added and the reaction mixture was refluxed for 20 h
m
(TLC monitoring), then another portion of pyridine/acetic acid was
added and the reaction was refluxed for 4 further hours. It was
cooled down to 0 ꢁC and the resulting precipitate was filtered and
washed with pentane to afford a light blue solid (147 mg; 68%).
Found: C 63.73, H 4.79, N 18.61. C20H19N5OS requires C 63.64, H
5.07, N 18.55%. Mp >300 ꢁC. IR (Nujol, cmꢀ1): 2223 (C^N), 1571
4.5.10.1. 2-((2,6-Diphenyl-4H-pyran-4-ylidene)methyl)thiazol-5-
carbaldehyde (26a). Yield: red solid (340 mg; 95%). Found: C 74.08,
H 4.05, N 4.17. C22H15NO2S requires C 73.93, H 4.23, N 3.92%. Mp
249e252 ꢁC. IR (Nujol, cmꢀ1): 1650 (C]O), 1641 (C]N), 1576 (C]
(C]C), 1540 (C]C). 1H NMR (300 MHz, CDCl3):
d
7.74 (d, J¼15.2 Hz,
C), 1554 (C]C, Ar). 1H NMR (400 MHz, CDCl3):
d 9.95 (s, 1H), 8.39
1H), 7.69 (s, 1H), 6.09 (d, J¼15.2 Hz, 1H), 3.75e3.65 (m, 4H),
(dd, J¼1.8 Hz, J0¼0.4 Hz, 1H), 8.33 (s, 1H), 7.96e7.91 (m, 2H),
7.84e7.81 (m, 2H), 7.56e7.48 (m, 6H), 6.62 (d, J¼1.8 Hz), 6.13 (s, 1H).
1.78e1.73 (m, 6H), 1.73e1.69 (m, 6H). 13C NMR (75 MHz, CDCl3):
d
177.0, 175.3, 174.5, 155.5, 139.0, 126.0, 113.3, 112.7, 112.2, 109.3,
13C NMR (100 MHz, CDCl3):
d 181.5, 174.4, 171.1, 156.5, 155.0, 153.7,
97.3, 51.0, 26.9, 25.8, 24.3. HRMS (ESIþ): found 378.1401 [MþH]þ.
C20H20N5OS requires 378.1383; found 400.1211 [MþNa]þ.
C20H19N5NaOS requires 400.1203.
138.5, 132.5, 132.2, 130.4, 130.2, 128.9, 128.9, 125.6, 125.1, 108.1,
104.7, 104.5. HRMS (ESIþ): found 358.0892 [MþH]þ. C22H16NO2S
requires 358.0896.
4.5.9. Compounds 24 and 25. General procedure. A solution of (2,6-
diphenyl-4H-pyran-4-yl)diphenylphosphine oxide (21) (2.0 g,
4.6 mmol) in anhydrous THF (45 mL) was cooled down to ꢀ78 ꢁC,
and n-BuLi (1.6 M in hexanes, 2.9 mL, 4.6 mmol) was added drop-
wise under argon atmosphere. After stirring for 25e30 min, a so-
lution of the corresponding thiazole carbaldehyde 22, 23 (520 mg,
4.5.10.2. (E)-3-(2-((2,6-Diphenyl-4H-pyran-4-ylidene)methyl)
thiazol-5-yl)acrylaldehyde (26b). Yield: red solid (316 mg; 83%).
Found: C 75.39, H 4.29, N 3.85. C24H17NO2S requires C 75.17, H 4.47,
N 3.65%. Mp 231e233 ꢁC. IR (Nujol, cmꢀ1): 1660 (C]O), 1646 (C]
N),1604 (C]N), 1578 (C]C, Ar),1543 (C]C, Ar). 1H NMR (400 MHz,
CDCl3):
d
9.61 (d, J¼7.7 Hz, 1H), 8.32 (d, J¼1.7 Hz, 1H), 7.96 (s, 1H),

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E. Galan et al. / Tetrahedron 68 (2012) 6427e6437
6436
7.94e7.90 (m, 2H), 7.84e7.80 (m, 2H), 7.60 (d, J¼15.3 Hz, 1H),
7.55e7.46 (m, 6H), 6.58 (d, J¼1.7 Hz, 1H), 6.35 (dd, J¼15.3 Hz,
125.9, 125.3, 123.8, 109.2, 104.3, 103.2, 82.6. HRMS (ESIþ): found
432.1160 [MþH]þ. C27H18N3OS requires 432.1165.
J0¼7.7 Hz, 1H), 6.06 (s, 1H). 13C NMR (75 MHz, CD2Cl2):
d 192.7, 171.0,
156.4, 154.9, 149.9, 142.0, 137.4, 133.2, 132.9, 131.4, 130.8, 130.6,
129.4, 129.4, 128.5, 126.0, 125.5, 108.4, 105.1, 104.8. HRMS (ESIþ):
found 384.1046 [MþH]þ. C24H18NO2S requires 384.1053.
4.5.11.3. 2-((2-((2,6-Diphenyl-4H-pyran-4-yliden)methyl)thiazol-
5-yl)methylene)malononitrile (8a). Reaction time: 6 h. Yield: dark
violet solid (29 mg; 37%). Found: C 74.27, H 3.55, N 10.22.
C25H15N3OS requires C 74.05, H 3.73, N 10.36%. Mp 262e265 ꢁC. IR
(Nujol, cmꢀ1): 2214 (C^N), 1651 (C]N). 1H NMR (400 MHz, CDCl3):
4.5.10.3. 5-((2,6-Diphenyl-4H-pyran-4-yliden)methyl)thiazol-2-
carbaldehyde (27a). Yield: maroon solid (309 mg; 87%). Found: C
74.21, H 4.10, N 4.03. C22H15NO2S requires C 73.93, H 4.23, N 3.92%.
Mp 239e243 ꢁC (dec). IR (Nujol, cmꢀ1): 1661 (C]O), 1649 (C]N).
d
8.56 (d, J¼1.7 Hz, 1H), 8.19 (s, 1H), 7.95e7.93 (m, 2H), 7.86e7.84
(m, 2H), 7.80 (s, 1H), 7.56e7.50 (m, 6H), 6.70 (d, J¼1.7 Hz, 1H), 6.13
(s, 1H). 13C NMR (100 MHz, CDCl3):
175.8, 157.6, 156.8, 156.3, 148.2,
d
1H NMR (300 MHz, CDCl3):
d
9.95 (s, 1H), 7.92 (s, 1H), 7.90e7.85 (m,
141.0, 132.2, 131.9, 130.8, 130.7, 129.1, 129.0, 127.0, 125.8, 125.3, 114.7,
113.9, 108.6, 105.7, 103.9, 74.6. HRMS (ESIþ): found 406.0993
[MþH]þ. C25H16N3OS requires 406.1009.
2H), 7.83e7.77 (m, 2H), 7.58e7.44 (m, 6H), 7.11 (d, J¼1.9 Hz, 1H),
6.58 (d, J¼1.9 Hz, 1H), 6.19 (s, 1H). 13C NMR (100 MHz, CDCl3):
d
183.4, 160.0, 155.7, 153.2, 145.1, 143.7, 134.5, 132.3, 132.2, 130.5,
130.0, 129.0, 128.9, 125.4, 124.8, 108.5, 102.9, 102.5. HRMS (ESIþ):
found 358.0862 [MþH]þ. C22H16NO2S requires 358.0896; found
380.0722 [MþNa]þ. C22H15NNaO2S requires 380.0716.
4.5.11.4. (E)-5-(3-(2-((2,6-Diphenyl-4H-pyran-4-ylidene)methyl)
thiazol-5-yl)allylidene)malononitrile (8b). Reaction time:
1
h
30 min. Yield: dark green solid (34 mg; 38%). Found: C 75.28, H
3.85, N 9.86. C27H17N3OS requires C 75.15, H 3.97, N 9.74%. Mp
229e230 ꢁC. IR (Nujol, cmꢀ1): 2217 (C^N), 1648 (C]N), 1540 (C]
4.5.10.4. (E)-3-(5-((2,6-Diphenyl-4H-pyran-4-ylidene)methyl)
thiazol-2-yl)acrylaldehyde (27b). Yield: red solid (143 mg; 37%).
Found: C 75.38, H 4.38, N 3.84. C24H17NO2S requires C 75.17, H 4.47,
N 3.65%. Mp 158e162 ꢁC. IR (Nujol, cmꢀ1): 1674 (C]O), 1653 (C]
C, Ar). 1H NMR (300 MHz, CD2Cl2):
d
8.47 (d, J¼1.4 Hz, 1H), 7.99 (s,
1H), 7.98e7.90 (m, 2H), 7.88e7.81 (m, 2H), 7.57e7.48 (m, 7H), 7.43
(d, J¼14.5 Hz, 1H), 6.77 (dd, J¼14.5 Hz, J0¼11.7 Hz, 1H), 6.66 (d,
N). 1H NMR (300 MHz, CDCl3):
d
9.73 (d, J¼7.7 Hz, 1H), 7.88e7.83
J¼1.4 Hz, 1H), 6.10 (s, 1H). 13C NMR (75 MHz, CD2Cl2):
d 172.4, 159.6,
(m, 2H), 7.83 (s, 1H), 7.81e7.75 (m, 2H), 7.63 (d, J¼15.8 Hz, 1H),
7.58e7.43 (m, 6H), 7.03 (d, J¼1.5 Hz, 1H), 6.81 (dd, J¼15.8 Hz,
J0¼7.7 Hz, 1H), 6.53 (d, J¼1.5 Hz, 1H), 6.14 (s, 1H). 13C NMR (75 MHz,
157.0, 155.6, 152.3, 140.1, 138.8, 133.1, 132.8, 132.1, 131.0, 130.8, 129.5,
129.4, 126.1, 125.6, 122.2, 114.9,113.0,108.7,105.6, 104.9, 79.8. HRMS
(ESIþ): found 432.1185 [MþH]þ. C27H18N3OS requires 432.1165.
CD2Cl2):
d 192.9, 158.7, 155.3, 152.9, 144.0, 143.6, 141.7, 133.1, 133.0,
132.8, 130.7, 130.2, 130.0, 129.4, 129.3, 125.7, 125.2, 108.8, 103.9,
102.8. HRMS (ESIþ): found 384.1048 [MþH]þ. C24H18NO2S requires
384.1053.
4.5.12. Compounds 9 and 10. General procedure. 1,3-Diethyl-2-
thiobarbituric acid (19) (56 mg, 0.28 mmol) and the correspond-
ing aldehydes 27a, 26a (100 mg, 0.28 mmol) were dissolved in
EtOH (3 mL) under argon atmosphere. The reaction mixture was
refluxed for 15e25 min (TLC monitoring) and then it was cooled
down to 0 ꢁC. Hexane was added and the resulting solid was filtered
and washed.
4.5.11. Compounds 7a,b and 8a,b. General procedure. The corre-
sponding aldehydes 26a,b, 27a,b (0.21 mmol) were dissolved in
EtOH (10 mL) under argon atmosphere and malononitrile (18)
(16 mg, 0.25 mmol) was added (piperidine (2 drops) was added for
the synthesis of 7a and 8a). The reaction mixture was refluxed for
1e6 h (TLC monitoring), then it was cooled down to room tem-
perature. In the case of 7a, after cooling, the precipitate was isolated
by filtration, washed with cold EtOH and dried. For 7b, 8a,b, the
solvent was evaporated and the crude was purified by flash chro-
matography (silica gel) using CH2Cl2 as eluent.
4.5.12.1. 5-((5-((2,6-Diphenyl-4H-pyran-4-ylidene)methyl)thia-
zol-2-yl)methylene)-1,3-diethyl-2-thioxodihydropyrimidine-4,6-
dione (9). Solvent for washing: first hexane, then CH2Cl2/MeOH.
Yield: green solid (74 mg; 48%). Found: C 66.94, H 4.46, N 7.90.
C30H25N3O3S2 requires C 66.77, H 4.67, N 7.79%. Mp 254e255 ꢁC. IR
(Nujol, cmꢀ1): 1651 (C]O), 1529 (C]C, Ar). 1H NMR (400 MHz,
CDCl3): d 8.84 (s, 1H), 8.21 (s, 1H), 8.02e7.97 (m, 2H), 7.86e7.81 (m,
4.5.11.1. 2-((5-((2,6-Diphenyl-4H-pyran-4-yliden)methyl)thiazol-
2-yl)methylene)malononitrile (7a). Reaction time: 1 h. Yield: dark
green solid (48 mg; 58%). Found: C 74.21, H 3.94, N 10.12.
C25H15N3OS requires C 74.05, H 3.73, N 10.36%. Mp 248e252 ꢁC
(dec). IR (Nujol, cmꢀ1): 2218 (C^N), 1651 (C]N). 1H NMR
2H), 7.57e7.48 (m, 7H), 6.71 (d, J¼1.9 Hz, 1H), 6.29 (s, 1H), 4.67 (q,
J¼6.9 Hz, 2H), 4.61 (q, J¼6.9 Hz, 2H), 1.41 (t, J¼6.9 Hz, 3H), 1.34 (t,
J¼6.9 Hz, 3H). 13C NMR was not registered due to its low solubility.
HRMS (ESIþ): found 540.1378 [MþH]þ. C30H26N3O3S2 requires
540.1410.
(400 MHz, CDCl3):
2H), 7.54e7.49 (m, 6H), 7.22 (d, J¼1.8 Hz, 1H), 6.67 (d, J¼1.8 Hz, 1H),
6.26 (s, 1H). 13C NMR (100 MHz, CDCl3):
157.0, 154.4, 151.5, 148.7,
147.4,144.8,136.7,131.9,131.8,130.9,130.4,129.1,129.0,125.4,125.0,
114.4, 113.8, 108.9, 103.2, 103.0. HRMS (ESIþ): found 406.1012
[MþH]þ. C25H16N3OS requires 406.1009.
d 8.00 (s, 1H), 7.91e7.89 (m, 3H), 7.83e7.80 (m,
4.5.12.2. 5-((2-((2,6-Diphenyl-4H-pyran-4-ylidene)methyl)thia-
zol-5-yl)methylene)-1,3-diethyl-2-thioxodihydropyrimidine-4,6-
dione (10). Solvent for washing: first EtOH, then CH2Cl2/hexane.
Yield: purple solid (125 mg; 84%). Found: C 66.54, H 4.86, N 7.98.
C30H25N3O3S2 requires C 66.77, H 4.67, N 7.79%. Mp 310e311 ꢁC. IR
(Nujol, cmꢀ1): 1646 (C]O), 1530 (C]C, Ar). 1H NMR (300 MHz,
d
4.5.11.2. (E)-2-(3-(5-((2,6-Diphenyl-4H-pyran-4-ylidene)methyl)
thiazol-2-yl)allylidene)malononitrile (7b). Reaction time: 3 h. Yield:
dark green solid (25 mg, 28%). Found: C 75.33, H 4.10, N 9.57.
C27H17N3OS requires C 75.15, H 3.97, N 9.74%. Mp 249e251 ꢁC. IR
(Nujol, cmꢀ1): 2218 (C^N), 1654 (C]N), 1581 (C]C, Ar), 1546 (C]
CDCl3, 320 K): d 8.74 (s, 1H), 8.65 (s, 1H), 8.50 (s, 1H), 8.04e7.82 (m,
4H), 7.63e7.49 (m, 6H), 6.73 (s, 1H), 6.22 (s, 1H), 4.72e4.55 (m, 4H),
1.43e1.30 (m, 6H). 13C NMR was not registered due to its low sol-
ubility. HRMS (ESIþ): found 540.1385 [MþH]þ. C30H26N3O3S2 re-
quires 540.1410.
C, Ar). 1H NMR (400 MHz, CD2Cl2):
d 7.94e7.90 (m, 2H), 7.86 (d,
J¼0.6 Hz, 1H), 7.47e7.45 (m, 2H), 7.59 (d, J¼10.8 Hz, 1H), 7.57e7.45
(m, 6H), 7.43 (d, J¼14.8 Hz, 1H), 7.36 (dd, J¼14.8 Hz, J0¼10.8 Hz, 1H),
7.08 (dd, J¼2.0 Hz, J0¼0.6 Hz, 1H), 6.64 (dd, J¼2.0 Hz, J0¼0.2 Hz, 1H),
Acknowledgements
Financial support from MICINN-FEDER (CTQ2008-02942,
CTQ2011-22727, MAT2008-06522-C02-02 and MAT2011-27978-
6.24 (s, 1H). 13C NMR (100 MHz, CD2Cl2):
d 158.9, 157.9, 156.2, 153.6,
ꢀ
145.4, 143.6, 140.8, 134.1, 133.0, 132.8, 130.9, 130.4, 129.5, 129.4,
C02-02) and Gobierno de Aragon-Fondo Social Europeo (E39) is

ꢀ
E. Galan et al. / Tetrahedron 68 (2012) 6427e6437
6437
H. B.; Epstein, J. A.; Girton, D. G.; Dries, L. S.; Taylor, R. E.; Barto, R. R., Jr.; Eades,
W.; Van Eck, T. E.; Moss, A. S.; Anderson, W. W. Adv. Funct. Mater. 2002, 12,
605e610.
gratefully acknowledged. A predoctoral fellowship to E.G. (CSIC, JAE
2008) is also acknowledged.
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Supplementary data
NMR and UVevis spectra of new compounds, X-ray crystallo-
graphic data and diagrams of the crystal structures of 4a and 6,
computed energies and Cartesian coordinates of optimized HF/6-
31G* geometries can be found. Supplementary data associated
with this article can be found in online version at http://dx.doi.org/
10.1016/j.tet.2012.05.123.
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