Donor-π-acceptor benzothiazole-derived dyes with an extended heteroaryl-containing conjugated system: synthesis, DFT study and antimicrobial activity

Article abstract of DOI:10.1016/j.tet.2008.08.064

A series of novel derivatives containing an electron-donating N,N-dimethylaminophenyl ring connected to an electron-withdrawing benzothiazole or benzothiazolium moiety via a heteroaryl system (furan, thiophene or N-methylpyrrole) and up to two ethenylene

Full text of DOI:10.1016/j.tet.2008.08.064

Tetrahedron 64 (2008) 10605–10618
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Donor–
p-acceptor benzothiazole-derived dyes with an extended
heteroaryl-containing conjugated system: synthesis, DFT study
and antimicrobial activity
a
a
,
b
,
a
c
a,
*
*
´
´
´ ´ ´ ´
, Peter Magdolen , Pavlına Foltınova , Pavol Zahradnık
Marian Zajac , Peter Hrobarik
a
´
Department of Organic Chemistry, Comenius University, Mlynska dolina, 84215 Bratislava, Slovakia
Department of Theoretical Chemistry, Slovak Academy of Sciences, Du´bravska cesta 9, 84536 Bratislava, Slovakia
Institute of Subcellular Biology, Comenius University, Mlynska dolina, 84215 Bratislava, Slovakia
b
c
´
´
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 26 June 2008
Received in revised form 31 July 2008
Accepted 21 August 2008
Available online 28 August 2008
A series of novel derivatives containing an electron-donating N,N-dimethylaminophenyl ring connected
to an electron-withdrawing benzothiazole or benzothiazolium moiety via a heteroaryl system (furan,
thiophene or N-methylpyrrole) and up to two ethenylene groups have been synthesized and charac-
terized. Furthermore, their nonlinear optical (NLO) properties have been investigated at the theoretical
level using DFT and time-dependent DFT methods, and their antimicrobial activities were evaluated
against a standard set of unicellular organisms. Both benzothiazole and benzothiazolium systems are
predicted to exhibit large NLO responses, based on the calculated static molecular quadratic hyper-
polarizabilities b0 as well as intramolecular charge transfer (ICT) transition characteristics. Moreover, the
3-alkyl-benzothiazolium salts were found to display high toxicity against several tested microbes.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Benzothiazole
Heterocycles
Carbaldehydes
C–C coupling
Nonlinear optics
Antimicrobial activity
1. Introduction
along the conjugation path between a donor and an acceptor.
However, such modification leads to a decrease of
b values (aro-
Organic molecules containing both an electron-donating group
(donor) and an electron-withdrawing group (acceptor) at opposite
ends of a conjugated p-electron system (often referred to as push–
pull systems) are of fundamental importance in materials chem-
istry since they serve as critical components for many advanced
technologies, such as nonlinear optical (NLO) devices,1 organic
light-emitting diodes (OLEDs),2 photovoltaic cells,3 etc. In such
matic rings disfavour an intramolecular charge transfer since it
requires them to adopt quinoidal-like structure). Theoretical as
well as experimental studies revealed that good thermal and
photochemical stabilities of NLO chromophores with preserved
high hyperpolarizabilities can be achieved by replacement of an
aromatic ring with easily delocalizable heteroaromatics.5–8
In respect of these findings, benzothiazole-derived dyes with
donor–
p
-acceptor systems, the donor and acceptor moieties pro-
a donor–p-acceptor setup are promising candidates for NLO ap-
vide the necessity of ground-state charge asymmetry, whereas the
plications.9 Several such systems containing benzothiazole as an
(auxiliary) electron-withdrawing group have already been syn-
p
-conjugated bridge provides a pathway for the redistribution of
electron density under the influence of external electric fields.4 For
the practical application of second-order NLO materials, not only
thesized, and relatively high values of hyperpolarizability
been reported for them.10,11 However, a further improvement in
values can be achieved by proper introduction of donor and ac-
b have
a high molecular quadratic hyperpolarizability
b
but also a good
b
thermal, chemical and photochemical stabilities are required. It is
well known that additional stability of a NLO chromophore can be
gained by substitution of the polyene segments by aromatic ones
ceptor substituents onto the benzothiazole core due to its non-
symmetric character,9,10 or by quaternization of the benzothiazole
nitrogen.12,13
To date, only a few organic salts have been studied for NLO
properties, because their electric charge prohibits their use in
a poling process. However, donor–p-acceptor organic salts exhibit
* Corresponding authors. Tel.: þ421 2 59410 487; fax: þ421 2 59410 444 (P.H.);
tel.: þ421 2 60296 342; fax: þ421 2 60296 690 (P.Z.).
extremely large NLO responses, substantially higher stabilities and
greater chromophore number densities in comparison with organic
poled NLO polymers.14 Furthermore, changing of the counterion
E-mail addresses: peter.hrobarik@savba.sk (P. Hroba´rik), zahradnik@fns.uniba.sk
´
(P. Zahradnık).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.08.064

10606
M. Zajac et al. / Tetrahedron 64 (2008) 10605–10618
can influence the crystal packing, with the aim of producing non-
centrosymmetric bulk structures, which are a prerequisite for
macroscopic second-order NLO effects. Thus, with the progress in
fabrication processes of materials, push–pull organic salts also
become applicable in NLO devices and could even replace con-
temporary NLO polymers.
Y
S
N
NMe2
NMe2
m
m
n
n
2
Y
S
N
Over the last few years, our research group synthesized a large
number of push–pull 3-alkyl-benzothiazolium salts 1 with differ-
3
R
X
ent number of ethenylene units in a
p-conjugated bridge and
various donor and alkyl substituents (Fig. 1).15a–c As some benzo-
thiazole-derived cyanine dyes were recognized to exhibit in-
teresting biological activities (like e.g., commercially available
dithiazanine, which is used as an anthelmintic and antiparasitic
drug),16 benzothiazolium salts 1 were primarily studied for their
antimicrobial toxicities. Those were analyzed by means of QSAR
methods to identify structural blocks responsible for high biological
Figure 2. Structures of target compounds. Y¼O, S, NMe; R¼methyl (M), allyl (A), prop-
2-ynyl (P); X¼I, Br; m¼0, 1; n¼0, 1.
structural units are connected via an ethenylene spacer. In the first
class, the synthetic approach starts with 2-heteroaryl-benzothia-
zoles, readily available via condensation of the corresponding
heteroaryl-2-carbaldehydes with 2-amino-thiophenol to form the
benzothiazole ring.18–20 The target compounds without any ethe-
nylene groups in the bridge system were prepared by an aryl–aryl
coupling reaction, starting from 2-(5-bromofuran-2-yl)benzothia-
zole 4a or 2-(5-bromothiophen-2-yl)benzothiazole 4b, which were
activity.17 It was shown that the length of the
p-conjugated bridge
between electron-donating group and benzothiazolium moiety as
well as the donor ability have a significant influence.
Recently, Coe et al.12 reported the results of Hyper-Rayleigh
scattering (HRS) measurements for 3-methyl-benzothiazolium
salts 1 (n¼1–4; R¼R0¼CH3) in comparison with the analogous
1-methylpyridinium salts. Experimental measurements revealed
that the static molecular quadratic hyperpolarizability b0 increases
with the length of polyene chain, and the benzothiazolium salts
exhibit larger NLO responses than their pyridinium analogues.
Aware of above mentioned results, we decided to extend our
series of push–pull 3-alkyl-benzothiazolium salts 3 as well as the
corresponding non-ionic benzothiazole derivatives 2, by in-
corporation of five-membered electron-rich heteroaromatics,
reacted with 4-(dimethylamino)phenylboronic acid
5 under
Suzuki-coupling conditions,21 catalyzed by palladium acetate, to
form 2a and 2b, respectively, in good yields (Scheme 1). Com-
pounds 2c and 2d were built using Wittig olefination.22 The starting
2-heteroarylbenzothiazoles 6a and 6b were formylated by the
Vilsmeier–Haack protocol to give the corresponding carbaldehydes
7a and 7b.23 Subsequently, the products smoothly underwent
a Wittig reaction with phosphonium iodide 8 (Scheme 1), providing
target compounds 2c (E:Z¼11:1) and 2d (E:Z¼16:1) in good yields.
At this point, it is fitting to mention that the phosphonium iodide 8
can be easily prepared by one-pot reaction of N,N-dimethylaniline,
formaldehyde, PPh3 and NaI, an approach introduced by Roncali et
al.24 However, the extended reaction time needed (3 weeks) was
easily reduced to 2 h, when the reaction was performed under
microwave irradiation (see Section 4).
namely furan, thiophene or N-methylpyrrole, into a
p-conjugated
bridge (Fig. 2). Such setting could lead to enhanced chemical,
photochemical and thermal stabilities, compared to derivatives
with a polyenic
p-bridge, and even to higher molecular quadratic
hyperpolarizabilities b0
.
Herein, we report the synthesis and characterization of title
systems 2 and 3. Furthermore, the structure/NLO–activity re-
lationships in selected systems are investigated using density
functional theory (DFT) and time-dependent DFT methods. Calcu-
lated hyperpolarizabilities b0 as well as intramolecular charge
transfer (ICT) transition characteristics are confronted with those of
the analogous benzothiazolium salts 1aM–dM (n¼1–4; R¼R0¼CH3).
Also, antimicrobial activities of all compounds prepared in this
work are evaluated against a standard set of unicellular organisms.
S
N
S
N
5
Y
Y
Br
NMe2
i)
2a, Y=O, 50%
2b, Y=S, 80%
4a, Y=O
4b, Y=S
S
N
S
N
Y
Y
CHO
ii)
6a, Y=O
6b, Y=NMe
7a, Y=O, 50%
7b, Y=NMe, 61%
2. Results and discussion
2.1. Synthesis of target structures
S
N
Y
8
NMe2
The synthesis of our target structures can be divided into two
separate tasks: (a) preparation of neutral (in the sense of non-ionic)
chromophores 2a–d with a direct connection between the benzo-
thiazole and the heteroaryl moiety, and (b) preparation of neutral
derivatives 2e–j and benzothiazolium salts 3, where these two
iii)
2c, Y=O, 76%
2d, Y=NMe, 50%
+
-
NMe2
(HO)2B
NMe2
I
Ph P
3
5
8
acceptor
-spacer
donor
NR'2
Scheme 1. Preparation of 2-(heteroaryl)benzothiazoles 2a–d. Reagents and condi-
tions: (i) Pd(OAc)2, PPh3, aq Na2CO3, THF, reflux; (ii) POCl3, DMF, 0 ꢀC to rt; (iii) Na,
MeOH, reflux.
S
N
n
To access derivatives 2e–j and 3a–f of the second class, with an
ethenylene spacer connecting the benzothiazole and the heteroaryl
functionalities, an aldol-type condensation reaction between
2-methylbenzothiazole or 2-methyl-3-alkyl-benzothiazolium salts
and suitable heteroaryl-2-carbaldehydes was proposed.15a–c,25 The
first set of aldehydes 10a–c was prepared by aryl–aryl coupling
R
X
1
Figure 1. Structure of push–pull 3-alkyl-benzothiazolium salts with
a
polyenic
p
-bridge: 1a (n¼1), 1b (n¼2), 1c (n¼3), 1d (n¼4). The N-alkyl substituents R are in-
dicated as capitals (M¼methyl, A¼allyl, P¼prop-2-ynyl) appended to the label of
corresponding compounds.

M. Zajac et al. / Tetrahedron 64 (2008) 10605–10618
10607
reactions. Under Suzuki-coupling conditions, 5-bromofuran-
2-carbaldehyde 9a and 5-bromothiophene-2-carbaldehyde 9b
reacted with 4-(dimethylamino)phenylboronic acid 5, yielding
carbaldehydes 10a and 10b, respectively, in good yields (Scheme 2).
With the carbaldehyde substrates 10a–f in hand, the proposed
aldol-type condensations were performed (Scheme 4). At first, in
reactions with 2-methylbenzothiazole 15, catalyzed by aqueous
KOH in DMSO at rt, 2-ethenylbenzothiazole derivatives 2e–j were
prepared in yields ranging from 43% up to 92% (Table 1).
5
Y
Y
Y
NMe2
OHC
OHC
Br
S
OHC
i)
CH3
+
NMe2
N
n
9a, Y=O
9b, Y=S
10a, Y=O, 51%
10b, Y=S, 80%
15
10a-f
Y
aq.KOH
DMSO, r.t.
Me
N
Me
N
S
N
NMe2
n
NMe2
ii), iii), iv)
2e-j, 43-92%
11
12, 72%
Scheme 4. Aldol-type condensations of heteroarylcarbaldehydes 10a–f with 2-
methylbenzothiazole.
Me
N
OHC
NMe2
v)
Table 1
10c, 72%
Preparation of benzothiazole derivatives 2e–j
Scheme 2. Preparation of 5-(4-dimethylaminophenyl)-heteroaryl-2-carbaldehydes
10a–c. Reagents and conditions: (i) Pd(OAc)2, PPh3, aq Na2CO3, THF, reflux; (ii) BuLi,
THF, ꢁ78 ꢀC to rt; (iii) ZnCl2, THF, rt; (iv) 4-bromo-N,N-dimethylaniline, Pd(PPh3)4, THF,
reflux; (v) POCl3, DMF, 0 ꢀC to rt.
Product
Y
n
Reaction time (h)
Yield (%)
2e
2f
2g
2h
2i
O
S
NMe
O
S
0
0
0
1
1
1
3.5
5
16
6
16
16
54
52
43
92
79
46
The same approach to form a 2-methylpyrrole 10c derivative was
found to be uneconomical, since 5-bromo-1-methylpyrrole-2-carbal-
dehyde is noteasy to prepare.26 Much betteroverallyields were obtained
with a Negishi-coupling reaction27 and a subsequent formylation.
N-Methylpyrrole was transformed into N-methylpyrrole-2-zinc chloride
and subsequently coupled with 4-bromo-N,N-dimethylaniline in a one-
pot reaction to give 2-(4-dimethylaminophenyl)-1-methylpyrrole 12 in
good yield. This was transformed into the carbaldehyde 10c by Vilsme-
ier–Haack reaction in good yield as well (Scheme 2).
The intermediates 10d–f were prepared from heteroaryl-2-car-
baldehydes 13a–c by Wittig reaction with phosphonium iodide 8,
yielding heteroarylstyrenes 14a–c in good yields as mixtures of
E and Z isomers, which were in turn formylated (Scheme 3). Under
Vilsmeier–Haack conditions, the aldehydes 10d–f were obtained in
only low yields as pure E isomers. As a better alternative, the car-
baldehyde 10e was synthesized also by an alternative method.
Lithiation of 14b and following reaction with DMF gave the product
in much higher yield, again as pure E isomer (Scheme 3).28
2j
NMe
Benzothiazolium derivatives 3aM–fA were obtained in
a similar manner from 3-alkyl-2-methylbenzothiazolium salts
16M–P and carbaldehydes 10a–f using pyridine as a base catalyst in
methanol at reflux (Scheme 5, Table 2). It is important to remark
that the products, as well as the starting aldehydes, have a rather
low solubility in common solvents, therefore in some cases the 3-
alkyl-2-methylbenzothiazolium salts were employed in excess to
remove all the aldehyde from the reaction mixture, furnishing the
product in good purity (see Section 4).
S
N
Y
OHC
CH3
+
NMe2
n
X
R
10a-f
16M, R = methyl, X = I
16A, R = allyl, X = Br
16P, R = prop-2-ynyl, X = Br
NMe2
Y
8
Y
CHO
i)
14a, Y=O, 62% (E:Z=3.5:1)
14b, Y=S, 63% (E:Z=3.5:1)
14c, Y=NMe, 50% (E:Z=2.5:1)
13a, Y=O
Y
pyridine
MeOH, reflux
13b, Y=S
S
NMe2
13c, Y=NMe
n
N
R
X
3aM-3fA
NMe2
Y
Scheme 5. Aldol-type condensations of heteroarylcarbaldehydes 10a–f with 3-alkyl-
2-methylbenzothiazolium salts 16M–P.
ii)
OHC
10d, Y=O, 36%
10e, Y=S,15%
2.2. DFT study of molecular structures
10f, Y=NMe, 20%
As all compounds under investigation (in the case of benzo-
thiazolium salts only the cationic part is assumed) can exist in at
least two different conformations, all conformers were taken into
account, and the electric properties (static quadratic hyper-
polarizabilities b0, ICT excitation energies Emax, adiabatic dipole
moment changes between the ground-state and the first excited
state Dm12, transition dipole moments m12 and oscillator strengths
fosc) were calculated by Boltzmann averaging.29,30 More details are
provided in Supplementary data (Tables S1–S3).
NMe2
S
iii), iv)
OHC
10e, 65%
Scheme 3. Preparation of 5-[4-(dimethylaminophenyl)vinyl]-heteroaryl-2-carbalde-
hydes 10d–f. Reagents and conditions: (i) Na, MeOH, reflux; (ii) POCl3, DMF, 0 ꢀC to rt;
(iii) BuLi, THF, 0 ꢀC; (iv) DMF, rt.

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M. Zajac et al. / Tetrahedron 64 (2008) 10605–10618
phenyl ring (torsion angle is 44ꢀ and 34ꢀ, respectively), all other
energy minima take up a fully planar arrangement (if hydrogen
atoms are not assumed). In the case of derivatives 2j and 3fM with
Table 2
Preparation of benzothiazolium salts 3aM–fA
Producta
Y
n
R
X
Reaction
time (h)
Yield (%)
an extended
p-conjugated bridge (n¼1), the repulsion between the
3aM
3aA
3aP
3bM
3bA
3cM
3cA
3cP
3dM
3dA
3eA
3fA
O
O
O
S
0
0
0
0
0
0
0
0
1
1
1
1
Methyl
Allyl
Prop-2-ynyl
Methyl
Allyl
Methyl
Allyl
Prop-2-ynyl
Methyl
Allyl
I
14
14
16
35
24
16
17
16
16
12
20
15
58
43
31
40
60
43
43
64
84
38
54
54
N-pyrrolic methyl and olefinic hydrogen atoms H10 and H15 is less
pronounced than in 2g and 3cM (n¼0) due to the larger distance
between them, which allows a coplanar arrangement of the 4-
dimethylaminostyryl moiety with the pyrrole ring. Here, the s-cis
orientation of both ethenylene spacers attached to the pyrrole ring
with the endocyclic double bonds (s2¼:(C9–C10–C11–C12)¼0ꢀ;
s3¼:(C13–C14–C15–C16)¼0ꢀ) is found to be the most stable. In
contrast to N-methylpyrrole, the energy minima of furan and
thiophene analogues (2e–f, 2h–i, 3aM–bM, 3dM–eM) favour the
s-trans arrangement (s2¼180ꢀ; s3¼180ꢀ) of both ethenylene spacers
with the endocyclic double bonds in the five-membered hetero-
aromatics. The stability of these conformers can be attributed to the
electrostatic through-space interaction of the lone pairs on oxygen/
sulfur atom with the positively charged hydrogens. However, the
Br
Br
I
Br
I
Br
Br
I
Br
Br
Br
S
NMe
NMe
NMe
O
O
S
Allyl
Allyl
NMe
a
N-alkyl groups abbreviations: M¼methyl, A¼allyl, P¼propargyl (prop-2-ynyl).
It is worthwhile mentioning that in all benzothiazolium salts
within the series 1, there is a significant gap (DE )
rel>15 kJ molꢁ1
s-trans orientation of C13]C14–C15]C16
(
s3¼180ꢀ) in both 3dM and
between the energetically lowest lying conformer (all-s-trans), that
is found in crystal structure,12,13 and the others, which therefore
contribute only marginally to averaged values of electric properties.
On the other hand, the energy differences between various con-
formers of 2-(heteroarylethenyl)benzothiazole derivatives 2e–j and
their N-alkylated salts 3, respectively, are smaller and thus contri-
butions from the other conformations are also substantial. The
optimized structures of the energetically most favoured con-
formers of 3-methylbenzothiazolium salts 3aM–fM are depicted in
3eM is found to be more stable only by 2 kJ molꢁ1 than in analogous
conformers with s3¼0ꢀ. This can be rationalized by the less positive
charge of vinyl hydrogen H16 in comparison with H9.
2.3. DFT study of static molecular quadratic
hyperpolarizabilities
The results of density functional theory (DFT) and time-de-
Figure 3. Irrespective of the length and constitution of a
p
-bridge,
pendent DFT calculations (both at B3LYP/6-31G level of theory) of
*
the s-trans conformation with s1¼:(N–C2–C9–C10)¼180ꢀ is pre-
ferred over s-cis (s1¼0ꢀ) within series 1 and 3. In contrast to ben-
zothiazolium salts, neutral benzothiazoles 2e–j energetically prefer
the s-cis (s1¼0ꢀ) arrangement of benzothiazole with the adjacent
ethenylene spacer. Apart from 2g and 3cM, which are non-planar
due to steric repulsion of N-pyrrolic methyl group with an attached
molecular quadratic hyperpolarizabilities b0 and ICT transition
characteristics are summarized in Tables 3 and 4.
Obviously, the relative trends in b0 values obtained by both
approaches, the finite-field (FF) derivative method and the two-
state model (cf. Tables 3 and 4), are parallel. That supports the
appropriateness of applicability of the simplified two-state model
Figure 3. Optimized geometries (bond distances are given in Angstroms) of 3-methylbenzothiazolium salts 3aM–fM; only conformers with the lowest energy are depicted.

M. Zajac et al. / Tetrahedron 64 (2008) 10605–10618
10609
Table 3
Calculated static molecular hyperpolarizabilities b0 (B3LYP/6-31G
*
) and ICT transition characteristics (time-dependent DFT, B3LYP/6-31G )
*
Compound
Y
n
b0a [10ꢁ30 esu]
EHOMO [eV]
ELUMO [eV]
Emax [eV]
Configuration
m12 [D]
Dm12 [D]
fosc
b0 [10ꢁ30 esu]
b
2e
2f
2g
2h
2i
O
S
NMe
O
S
0
0
0
1
1
1
158
193
131
227
313
249
ꢁ4.71
ꢁ4.83
ꢁ4.65
ꢁ4.61
ꢁ4.69
ꢁ4.43
ꢁ1.85
ꢁ1.98
ꢁ1.61
ꢁ1.98
ꢁ2.13
ꢁ1.78
2.72
2.66
2.90
2.49
2.43
2.56
0.629 (HOMO/LUMO)
0.631 (HOMO/LUMO)
0.627 (HOMO/LUMO)
0.624 (HOMO/LUMO)
0.624 (HOMO/LUMO)
0.619 (HOMO/LUMO)
11.3
12.0
11.5
12.3
13.6
14.5
14.6
15.0
14.7
15.1
16.3
14.1
1.319
1.465
1.452
1.445
1.715
2.036
296
356
271
431
599
530
2j
NMe
a
Calculated by using the finite-field numerical derivative method.
Estimated from the two-state model (see Section 4.5).
b
Table 4
Calculated static molecular hyperpolarizabilities b0 (B3LYP/6-31G
*
) and ICT transition characteristics (time-dependent DFT, B3LYP/6-31G )
*
Compound
Y
n
b0a [10ꢁ30 esu]
EHOMO [eV]
ELUMO [eV]
Emax [eV]
Configuration
m12 [D]
Dm12 [D]
fosc
b0 [10ꢁ30 esu]
b
1aM
1bM
1cM
1dM
3aM
3bM
3cM
3dM
3eM
3fM
d
d
d
d
O
1
2
3
4
0
0
0
1
1
1
78
142
233
357
230
289
329
381
463
465
ꢁ8.18
ꢁ7.78
ꢁ7.45
ꢁ7.18
ꢁ7.57
ꢁ7.54
ꢁ7.44
ꢁ7.28
ꢁ7.25
ꢁ7.09
ꢁ5.53
ꢁ5.47
ꢁ5.41
ꢁ5.33
ꢁ5.46
ꢁ5.49
ꢁ5.29
ꢁ5.38
ꢁ5.41
ꢁ5.14
2.72
2.45
2.23
2.05
2.19
2.14
2.14
2.00
1.96
2.05
0.591 (HOMO/LUMO)
0.578 (HOMO/LUMO)
0.567 (HOMO/LUMO)
0.558 (HOMO/LUMO)
0.585 (HOMO/LUMO)
0.584 (HOMO/LUMO)
0.603 (HOMO/LUMO)
0.576 (HOMO/LUMO)
0.572 (HOMO/LUMO)
0.581 (HOMO/LUMO)
12.0
14.6
17.1
19.4
13.0
13.9
12.3
14.6
16.0
15.8
6.2
7.8
8.8
1.481
1.984
2.465
2.936
1.395
1.584
1.220
1.617
1.915
1.949
141
324
604
1019
540
683
782
943
1160
1274
9.8
13.2
13.8
20.4
15.2
15.0
18.4
S
NMe
O
S
NMe
a
Calculated by using the finite-field numerical derivative method.
Estimated from the two-state model (see Section 4.5).
b
in order to gain a better understanding of the structure–activity
relationships in all compounds under investigation.
Some structural aspects that influence the NLO activity are
discussed here.
It is well known that most of the total hyperpolarizability in
donor–p-acceptor organic systems is associated with ICT (intra-
2.3.1. Length of the p-conjugated bridge
molecular charge transfer) transitions. The CI (configuration in-
teraction) coefficients calculated by time-dependent DFT reveal that
the lowest energy excitations Emax correspond in everycase with the
HOMO–LUMO transitions (cf. Tables 3 and 4). For all compounds
Theoretical calculations reproduce the expected optical behav-
iour in the studied set of compounds. Increasing the length of
polyene chain in the set 1aM–dM (Table 4) is accompanied by the
decrease in Emax, along with increases in m12, Dm12, fosc, that leads to
studied here, both HOMO and LUMO are
p
-type orbitals, which
enhanced NLO response (larger b0 values). The same holds also for
2-heteroaryl derivatives within the both series 2 and 3. The only
exception is observed in Dm12 passing from 2g to 2j and 3cM to 3fM,
respectively, which can be rationalized by non-planar structures of
2g and 3cM.
appearanceis demonstrated for3fM in Figure4. TheHOMOismainly
constrained to the donor part, i.e., the 4-dimethylaminophenyl
moiety, whereas the LUMO has its largest atomic orbital (AO) co-
efficients at the atoms of the electron-withdrawing thiazole/thia-
zolium ring and adjacent ethenylene group. However, other carbon
atoms in a
p
-conjugated bridge with incorporated heteroaromatics
2.3.2. Polyene versus heteroaryl-containing spacer
also contribute to both HOMO and LUMO, leading to an extensive
overlap of those frontier orbitals, and thus to large values of transi-
tion dipole moments m12. Neutral benzothiazole derivatives render
a similar picture.
If the five-membered heteroaromatics are viewed as an equiv-
alent of two ethenylene units (or s-cis-buta-1,3-diene fragment), it
is evident from Table 4, that 2-(heteroarylethenyl)benzothiazolium
salts 3 display comparable (Y¼O) or even larger (Y¼S, NMe) b0
values compared to their analogues with a genuine polyenic chain
1. Although smaller transition dipole moments m12 are computed
for 2-(heteroarylethenyl)benzothiazolium salts 3, their enhanced
NLO response results from considerable larger change in dipole
moment Dm12 upon ICT excitation. This implies a slightly different
origin of b0 values, which can be understood from the following:
electron-rich heterocycles (furan, thiophene, N-methylpyrrole) in
the ground-state suppress an electron transfer from a 4-dimethyl-
amino-phenyl moiety to an electron-withdrawing (benzothiazole/-
ium) group due to their aromatic character, and therefore larger
change in dipole moment upon ICT excitation is observed. On the
other hand, smaller overlap of HOMO and LUMO orbitals, resulted
from the same reason as enhancement of Dm12, leads to a smaller
transition moment m12
.
2.3.3. Benzothiazole versus benzothiazolium derivatives
Calculated b0 values indicate somewhat (ca. two times) larger
NLO response of ionic 3aM–fM chromophores compared to their
neutral analogues 2e–j (cf. Tables 3 and 4). Here, enhanced NLO
response of benzothiazolium compounds can be explained by their
Figure 4. Frontier molecular orbitals HOMO and LUMO (isosurface þ/ꢁ0.03 a.u.) in the
benzothiazolium salt 3fM.

10610
M. Zajac et al. / Tetrahedron 64 (2008) 10605–10618
Table 5
2.3.5. Solvent effects
Calculated static molecular hyperpolarizabilities b0 (B3LYP/6-31G
*
) and ICT transi-
Since the hyperpolarizability values are also markedly influ-
enced by the solvent effects, DFT calculations with the inclusion of
bulk solvent effects by the polarizable continuum model (PCM)
were also performed for benzothiazolium salts (methanol as a sol-
tion characteristics (time-dependent DFT, B3LYP/6-31G
(CH3OH as a solvent)
*
) using PCM solvation model
Compound b0 [10ꢁ30 esu] Emax [eV] m12 [D] Dm12 [D] fosc
b0c [10ꢁ30 esu]
a
b
1aM
1bM
1cM
1dM
3aM
3bM
3cM
3dM
3eM
3fM
289
628
1192
2059
871
1218
955
1580
2299
1740
2.61 (2.37) 12.7
2.32 (2.19) 15.5
2.09 (2.13) 18.1
1.90 (2.11) 20.6
2.12 (2.13) 13.8
2.07 (2.20) 14.9
2.15 (2.21) 13.6
1.90 (2.09) 15.0
6.5
7.8
8.6
1.604
2.102
180
408
vent;
3
¼32.63). The results are gathered in Table 5. Generally, b0
values calculated by employing PCM solvation model are higher in
comparison with those in vacuo (cf. Table 4), which can be mainly
attributed to smaller excitation energies and larger transition mo-
2.584 757
3.059 1259
1.540 598
9.2
12.1
12.9
17.5
13.4
14.0
15.2
1.746
1.514
1.630
784
818
973
ments m12. Nevertheless, the trends in
b values are parallel with
those obtained in vacuo, apart from the fact that finite-field b0
values are superior to those estimated from the two-state model.
In addition, the calculated Emax values are compared with the
experimental ones measured in methanol solution (Table 5). Al-
though a qualitative agreement is found, the calculations predict
1.86
2.00
16.8
17.3
1.995 1341
2.255 1335
a
Calculated by using the finite-field numerical derivative method.
Experimental values are given in parenthesis.
Estimated from the two-state model (see Section 4.5).
b
c
a greater extent of red-shifting of the ICT bands with a
p-bridge
elongation (for instance, the calculated value of Emax on moving
D
from 3aM to 3dM is 0.22 eV, whereas that observed is only 0.04 eV).
much lower excitation energies Emax, as well as slightly larger
transition moments m12
.
Although non-ionic benzothiazole derivatives 2e–j are pre-
dicted to exhibit smaller static molecular hyperpolarizabilities b0
compared to their N-alkylated analogues, a functionalization of the
N-alkyl donor with hydroxyethyl groups would allow their use as
monomers in the synthesis of interesting NLO polymers.
2.4. Biological activity
Prepared benzothiazole derivatives 2 and benzothiazolium salts
3 were tested in vitro for their antimicrobial activity against uni-
cellular flagellate Euglena gracilis, as well as some Gram-positive
and Gram-negative bacteria, a yeast and a mould (see Section 4).
The log(1000/ED50) values, where ED50 is the dosage producing
a desired effect in half the test population (in 10ꢁ3 mol Lꢁ1), and
2.3.4. Character of heteroaryl moiety
According to computed b0 values, thiophene- and N-methyl-
pyrrole-containing derivatives are expected to be the most NLO-
active. While the former is more efficient in neutral benzothiazoles,
the latter leads to the highest b0 values in benzothiazolium salts.
However, as the calculated b0 values of pyrrole- and thiophene-
containing derivatives are in a narrow range of numerical values,
the ordering of the structures according to their calculated NLO
responses must not be necessarily consistent with experimental
observation.
minimum inhibitory concentrations (MIC in
Table 6.
mg/mL) are collected in
It is evident that all benzothiazolium salts 3 exhibit much higher
antimicrobial activities than the neutral benzothiazole derivatives
2, a fact observed already in our previous studies.15,17 Better solu-
bility of benzothiazolium salts in a polar medium, and therefore
easier transport of the substrate into the cellular environment, is
presumably responsible for higher toxicity of these compounds.
Table 6
Antimicrobial activities of tested benzothiazole derivatives 2a–j and benzothiazolium salts 3aM–fA in comparison with 1aM–cM
Compound
Eugena
gracilisa
Gram-positive bacteria
Gram-negative bacteria
Yeast
Mould
Staphylococcus
aureusb
Bacilus
Escherichia
colib
Pseudomonas
Candida
Microsporum
gypseumc
subtilisb
aeruginosab
albicansb
2a
2b
2c
2e
2f
2g
2h
2i
2.482
2.878
2.933
2.886
2.910
2.965
2.985
2.983
2.999
50
50
50
50
50
50
50
50
50
250
250
250
250
250
250
250
50
>250
>250
>250
>250
>250
>250
>250
>250
>250
>250
>250
>250
>250
>250
>250
>250
>250
>250
250
250
250
250
250
250
250
250
250
>250/250
>250/250
>250/250
>250/250
>250/250
>250/250
>250/250
>250/250
>250/250
2j
250
1aM
1bM
1cM
6.135
6.437
6.976
2
10
2
50
50
10
250
250
50
>250
>250
>250
50
50
50
50/10
50/10
5/2.5
3aM
3aA
3aP
3bM
3bA
3cM
3cA
3cP
3dM
3dA
3eA
3fA
6.480
6.428
6.410
6.563
6.533
6.590
6.508
6.612
6.575
6.557
6.571
6.484
10
2
2
10
2
2
2
2
10
2
2
50
10
10
50
10
10
10
10
50
50
10
10
250
250
250
250
250
50
50
50
250
250
50
>250
>250
>250
>250
>250
>250
>250
>250
>250
>250
>250
>250
250
50
50
250
50
10
10
10
50
50
10
50/10
10/2
10/2
50/10
50/10
10/2
10/2
10/2
50/10
10/2
2/0.4
2/0.4
2
50
10
a
Values given as log(1000/ED50).
Values for minimum inhibitory concentration (MIC) in
Fungicide/fungistatic concentration in g/mL.
b
c
mg/mL.
m

M. Zajac et al. / Tetrahedron 64 (2008) 10605–10618
10611
The toxicity values of the title structures 3 against the unicellular
flagellate E. gracilis are in general comparable to those of benzo-
thiazolium salts 1aM–cM. The highest toxicities were exhibited by
compounds 3cM (6.590, Y¼O, R¼Me, n¼0) and 3cP (6.612, Y¼NMe,
R¼Me, n¼0) and are somewhat lower compared with the structure
1cM (6.955, n¼3). The inclusion of heteroaryl moiety into
were removed by rotary evaporation. The starting compounds 4a,18
4b,19 5,31 6a,20 6b,20 9a,32 9b,33 13b33a and 13c34 were prepared
according to known literature procedures.
The 1H and 13C NMR spectra were recorded on a Varian Gemini
300 spectrometer, operating at 300 MHz (1H) and 75 MHz (13C)
with TMS as internal standard. Chemical shifts
d are referred in
a
p
-conjugated bridge slightly enhances the antimicrobial activity,
terms of parts per million and J-coupling constants are given in
hertz. Abbreviations for multiplicity are as follows: s (singlet),
d (doublet), t (triplet), q (quadruplet), m (multiplet). IR-spectra
were recorded on a Carl Zeiss/Jena Specord M 80 instrument or
Perkin Elmer Spectrum One FTIR with an Universal ATR Sampling
Accessory and the signals are given by wave numbers (cmꢁ1). UV–
vis absorption maxima were measured on a HP Diode Array 8245
spectrometer. Combustion analysis was measured on a Carlo Erba
Science 1106 instrument. The melting points were measured using
a Kofler apparatus and were not corrected.
but not as much as an inclusion of two ethenylene units. Thus,
unlike the effect observed in the NLO properties, the five-mem-
bered heteroaromatic fragment is not equivalent to two ethenylene
units in the terms of resulting toxicity. In general, the sensitivity of
Gram-positive bacteria to the tested substances is higher than that
of Gram-negative bacteria. The strongest antibacterial effect was
found for Staphylococcus aureus. Moreover, derivatives 3eA (Y¼S,
R¼Me, n¼1) and 3fA (Y¼NMe, R¼Me, n¼1) display interesting
fungicidal/fungistatic activity against Microsporum gypseum and
could be considered as new potential antifungal substances.
4.2. Synthesis
3. Conclusions
4.2.1. (40-Dimethylaminobenzyl)triphenylphosphonium iodide (8)
A suspension, containing N,N-dimethylaniline (10 g, 82 mmol,
1 equiv), 37% aqueousformaldehydesolution(8.2 g, 82 mmol,1 equiv),
PPh3 (21.5 g, 82 mmol, 1 equiv), NaI (12.3 g, 82 mmol, 1 equiv), acetic
acid (15.6 mL) and chloroform (60 mL), was stirred for 15 min at rt.
Afterwards, a few drops of water were added and the mixture was
heated in a microwave reactor (400 W) to reflux for 2 h and sub-
sequently left to stand at rt overnight. The chloroform was evaporated,
150 mL of water was added, the insoluble residue collected by filtra-
tion, washed several times with water and diethyl ether and dried in
vacuum. The reaction yielded 32.5 g of white solid (76%). Mp 238–
A series of novel donor–
(2 and 3) with an extended heteroaryl-containing
p
-acceptor benzothiazole-derived dyes
-conjugated
p
system have been synthesized and characterized. Fast and effective
access to the target compounds was accomplished through
the combination of palladium-catalyzed aryl coupling reactions,
Wittig olefination, Vilsmeier–Haack formylation and aldol-type
condensations.
Selected target structures were investigated for their molecular
nonlinear optical (NLO) properties at the theoretical level using DFT
and time-dependent DFT methods. A pronounced conformational
effect on calculated static quadratic hyperpolarizabilities b0 was
found for 2-(heteroarylethenyl)benzothiazole/-ium derivatives
(2 and 3). Pursuant to this finding, the influence of conformational
equilibria on b0 values should be taken into account in further
studies of related systems.
239 ꢀC (lit. 240 ꢀC);24 1HNMR(CDCl3)
d
¼7.83–7.75 (m, 3H, Ar–H), 7.69–
7.62 (m, 12H, Ar–H), 6.85 (dd, 2H, J¼8.9, 2.5 Hz, Ar–H), 6.46 (d, 2H,
J¼8.6 Hz, Ar–H), 4.93 (d, 2H, J¼13.0 Hz, CH2), 2.88 (s, 6H, NMe2) ppm.
4.2.2. 5-(Benzothiazol-2-yl)-furan-2-carbaldehyde (7a)
All the compounds under investigation could be considered as
efficient NLO-phores due to their very large b0 values. The benzo-
thiazolium salts 3aM–fM are predicted to exhibit somewhat larger
molecular quadratic NLO responses compared to their non-ionic
analogues 2e–j. In general, it was shown that inclusion of a five-
To a solution of furan derivative 6a (0.8 g, 4 mmol, 1 equiv) in
dry DMF (2 mL), cooled in an ice bath, POCl3 (0.84 mL, 1.38 g,
9 mmol, 2.25 equiv) was added with stirring. The reaction mixture
was stirred for 1 h at rt and 3 h at 80 ꢀC. After this time, the mixture
was allowed to cool and was poured on ice and neutralized with
aqueous solution of NaOH. The precipitated solid was collected by
filtration. The crude product was purified by column chromato-
graphy (SiO2, hexanes/EtOAc¼4:1) to give 0.45 g of beige solid
membered heteroaryl moiety into a
stantially enhances the NLO response of the donor–
p
-conjugated bridge sub-
-acceptor
p
systems. In this respect, benzothiazole-based chromophores con-
taining N-methylpyrrole-2,5-diyl or thiophene-2,5-diyl spacer are
predicted to be superior to those derived from furan.
In addition, the antimicrobial activities of the title systems (2
and 3) were evaluated against a standard set of unicellular organ-
isms. The title structures 3 exhibit high toxicity values against the
unicellular flagellate E. gracilis, as well as some interesting anti-
bacterial and fungicidal activities. The studied systems were found
to be comparably active than the previously prepared benzothia-
(50%). Mp 175–176 ꢀC (lit. 176 ꢀC);23 1H NMR (CDCl3)
d¼9.81 (s, 1H,
CHO), 8.12 (d, 1H, J¼8.2 Hz, HBT), 7.97 (d, 1H, J¼8.0 Hz, HBT), 7.56 (dt,
1H, J¼8.2, 1.1 Hz, HBT), 7.47 (ddd, 1H, J¼8.2, 8.0, 1.1 Hz, HBT), 7.40 (d,
1H, J¼3.8 Hz, HFUR), 7.36 (d, 1H, J¼3.6 Hz, HFUR) ppm.
4.2.3. 5-(Benzothiazol-2-yl)-1-methylpyrrole-2-carbaldehyde (7b)
To a solution of pyrrole derivative 6b (0.3 g,1.4 mmol,1 equiv) in
dry DMF (5 mL), cooled in an ice bath, POCl3 (0.38 mL, 0.63 g,
4.2 mmol, 3 equiv) was added with stirring. The reaction mixture
was stirred for 30 min at rt and 1 h at 80 ꢀC. After this time, the
mixture was allowed to cool and was poured on ice and neutralized
with aqueous solution of NaOH. The mixture was extracted with
chloroform (3ꢂ20 mL), combined organic layers were washed with
brine, dried (Na2SO4) and evaporated to give the crude product,
which was purified by column chromatography (SiO2, hexanes/
EtOAc¼4:1) to yield 0.2 g of beige solid (61%). Mp 188–190 ꢀC; 1H
zolium salts containing polyene p-conjugated bridge (1aM–cM).
Moreover, the preparedheteroaryl-2-carbaldehydeintermediates
10a–f can serve as valuable and versatile building blocks for the
synthesis of molecules with an extended
p-conjugated system,
finding potential application in many fields of material chemistry,
such as optical and electronic devices.
4. Experimental
4.1. General
NMR (CDCl3)
1H, J¼8.1 Hz, HBT), 7.52 (t, 1H, J¼8.2 Hz, HBT), 7.42 (t, 1H, J¼7.1 Hz,
BT), 6.98 (d, 1H, J¼4.1 Hz, HPYR), 6.84 (d, 1H, J¼4.2 Hz, HPYR), 4.49
(s, 3H, CH3–N) ppm; 13C NMR (CDCl3)
d
¼9.71 (s,1H, CHO), 8.07 (d,1H, J¼8.1 Hz, HBT), 7.90 (d,
H
Purchased chemicals and solvents were purified by distillation
or crystallization and dried as needed, using standard procedures.
For TLC and column chromatography, a mixture of hexane isomers
(hexanes, light petroleum) was used in eluent solutions. Solvents
d
¼179.2, 160.1, 154.4, 133.9,
132.8, 132.5, 125.9, 125.3, 124.5, 122.5, 121.0, 115.1, 34.9 ppm. Anal.
Calcd for C13H10N2OS: C 64.44, H 4.16, N 11.56; found: C 64.25, H
4.30, N 11.48%.

10612
M. Zajac et al. / Tetrahedron 64 (2008) 10605–10618
4.2.4. 2-[5-(4-Dimethylaminophenyl)-furan-2-yl]-
benzothiazole (2a)
(CHCl3) lmax¼414 nm (log
3
¼6.450); IR (MeOH) ¼1520, 1410, 1340,
n
920 cmꢁ1. Anal. Calcd for C21H18N2OS: C 72.80, H 5.24, N 8.09;
found: C 72.58, H 5.07, N 7.80%.
To a solution containing the boronic acid 5 (0.3 g, 1 mmol,
1.0 equiv), arylbromide 4a (0.21 g, 1.3 mmol, 1.3 equiv), Pd(OAc)2
(2 mg, 0.01 mmol, 0.01 equiv) and PPh3 (8 mg, 0.03 mmol,
0.03 equiv), in THF (7 mL) under nitrogen, 2 M aqueous Na2CO3
solution (3 mL) was added and the mixture was heated to reflux for
16 h. After this time, 20 mL of water was added and the mixture
was extracted with ethyl acetate (2ꢂ10 mL), combined organic
layers were dried (Na2SO4) and evaporated. The crude product was
purified by column chromatography (SiO2, hexanes/EtOAc¼4:1) to
yield 0.16 g of sightly yellow solid (50%). Mp 188–190 ꢀC; 1H NMR
4.2.7. 2-{5-[2-(4-Dimethylaminophenyl)-vinyl]-1-methylpyrrol-2-
yl}-benzothiazole (2d)
A sodium methanolate solution, prepared from sodium (16 mg,
0.68 mmol,1.1 equiv) and dry MeOH (2 mL), was added dropwise to
a stirred suspension of phosphonium iodide 8 (0.36 g, 0.68 mmol,
1.1 equiv) in MeOH (2 mL) at rt. The mixture was stirred for 15 min,
a solution of aldehyde 7b (0.15 g, 0.62 mmol, 1 equiv) in MeOH
(5 mL) was added and the reaction mixture was then set to reflux
for 4 h. After cooling to ambient temperature, the solvent was
evaporated, the residue was mixed with water (10 mL) and
extracted with chloroform (3ꢂ10 mL). Combined organic layers
were dried (Na2SO4), the solvent was evaporated and the crude
product was purified by column chromatography (SiO2, hexanes/
EtOAc¼4:1) to give 0.11 g of orange solid (E:Z isomer¼16:1, overall
(CDCl3)
d
¼8.02 (d, 1H, J¼8.6 Hz, HBT), 7.87 (d, 1H, J¼8.1 Hz, HBT),
7.68 (d, 2H, J¼9.0 Hz, H2Ph, H6Ph), 7.47 (t, 1H, J¼8.4 Hz, HBT), 7.35 (t,
1H, J¼8.1 Hz, HBT), 7.26 (d, 1H, J¼3.7 Hz, H3FUR), 6.76 (d, 2H,
J¼9.0 Hz, H3Ph, H5Ph), 6.62 (d, 1H, J¼3.7 Hz, H4FUR), 3.03 (s, 6H,
NMe2) ppm; 13C NMR (CDCl3)
d
¼157.7, 157.3, 153.9, 134.0, 126.5,
126.2, 125.7, 124.6, 124.5, 122.6, 121.9, 121.3, 113.9, 112.0, 104.9,
40.4 ppm; IR (MeOH)
n
¼2920, 1612, 1596, 1499, 1431, 1362, 1195,
yield 50%). (E)-isomer: mp 189–191 ꢀC; 1H NMR (CDCl3)
d¼7.92 (d,
905 cmꢁ1. Anal. Calcd for C19H16N2OS: C 71.22, H 5.03, N 8.74;
found: C 71.41, H 5.14, N 8.52%.
1H, J¼8.0 Hz, HBT), 7.80 (d, 1H, J¼7.7 Hz, HBT), 7.42 (m, 1H, HBT), 7.40
(d, 2H, J¼8.5 Hz, H2Ph, H6Ph), 7.29 (ddd, 1H, J¼8.5, 8.0, 0.9 Hz, HBT),
6.99 (d, 1H, J¼16.2 Hz, C]CHb), 6.85 (d, 1H, J¼4.4 Hz, H3PYR), 6.75
(d,1H, J¼15.7 Hz, C]CHa), 6.72 (d, 2H, J¼8.8 Hz, H3Ph, H5Ph), 6.50 (d,
4.2.5. 2-[5-(4-Dimethylaminophenyl)-thiophen-2-yl]-
benzothiazole (2b)
1H, J¼4.4 Hz,
NMe2) ppm; 13C NMR (CDCl3)
129.2,126.5,125.8,124.9,124.6, 123.2,121.2, 120.0,114.7, 111.5, 111.0,
105.5, 39.5, 32.1 ppm; UV–vis (CHCl3) lmax¼390 nm (log ¼6.38),
H4PYR), 4.23 (s, 3H, CH3–NPYR), 3.00 (s, 6H,
To a solution containing the boronic acid 5 (0.3 g, 1 mmol,
1.0 equiv), arylbromide 4b (0.20 g, 1.2 mmol, 1.2 equiv), Pd(OAc)2
(2 mg, 0.01 mmol, 0.01 equiv), and PPh3 (8 mg, 0.03 mmol,
0.03 equiv) in THF (7 mL) under nitrogen, 2 M aqueous Na2CO3
solution (3 mL) was added and the mixture was heated to reflux for
16 h. After this time, the mixture was allowed to cool to ambient
temperature, the precipitated solid was collected by filtration,
washed with diethyl ether and cold acetone and dried under vac-
uum to give 0.27 g of yellow solid (80%). Mp 219–220 ꢀC (lit. 211–
d
¼159.5, 153.4, 137.9, 132.8, 129.2,
3
518 nm (log
3
¼5.60); IR (MeOH) ¼1610, 1550, 1520, 1430, 1360,
n
910 cmꢁ1. Anal. Calcd for C22H21N3S: C 73.50, H 5.89, N 11.69;
found: C 73.33, H 6.05, N 11.48%.
4.2.8. 2-(4-Dimethylaminophenyl)-1-methylpyrrole (12)
To a solution of 1-methylpyrrole (0.65 g, 8 mmol, 1 equiv) in dry
THF (10 mL) under nitrogen, cooled to ꢁ78 ꢀC, a solution of
n-butyllithium in hexanes (5 mL,1.6 M, 8 mmol,1 equiv) was added
dropwise. The mixture was stirred for 5 min at ꢁ78 ꢀC, allowed to
warm to rt and was stirred for another 30 min. Afterwards a solu-
tion of ZnCl2 in THF (8 mL, 1 M, 8 mmol, 1 equiv) was added and the
mixture was stirred for 90 min at rt. The resulting solution was
added via a syringe to a second flask, charged with 4-bromo-N,N-
dimethylaniline (1.6 g, 8 mmol, 1 equiv) and [Pd(PPh3)4] (185 mg,
0.16 mmol, 0.02 equiv) under nitrogen. The mixture was heated to
reflux for 60 h, was allowed to cool and saturated aqueous NH4Cl
solution (5 mL) was added. After a while, the mixture was diluted
with water, mixed with aqueous Na2CO3 solution (50 mL) and
extracted with ethyl acetate (3ꢂ50 mL). Combined organic layers
were washed with brine, dried (Na2SO4) and evaporated. The crude
product was purified with column chromatography (SiO2, hexanes/
EtOAc¼5:1) to yield 1.16 g of beige solid (72%). Mp 66–67 ꢀC; 1H
212 ꢀC);11b 1H NMR (CDCl3)
d
¼8.01 (d, 1H, J¼8.1 Hz, HBT), 7.83 (d,
1H, J¼8.4 Hz, HBT), 7.58 (d, 1H, J¼3.7 Hz, H3THP), 7.56 (d, 2H,
J¼8.8 Hz, H2Ph, H6Ph), 7.45 (ddd, 1H, J¼8.2, 7.3, 1.1 Hz, HBT), 7.34
(ddd,1H, J¼8.2, 8.0,1.1 Hz, HBT), 7.18 (d,1H, J¼4.0 Hz, H4THP), 6.74 (d,
2H, J¼8.9 Hz, H3Ph, H5Ph), 3.02 (s, 6H, NMe2) ppm; 13C NMR (CDCl3)
d
¼161.8, 154.0, 150.8, 149.8, 134.8, 133.8, 130.0, 127.2, 126.5, 125.1,
122.9, 121.9, 121.7, 121.6, 112.6, 40.5 ppm; UV–vis (CHCl3)
lmax¼406 nm (log
3
¼6.510); IR (MeOH) ¼1610, 1520, 1460, 1430,
n
1350, 920 cmꢁ1. Anal. Calcd for C19H16N2S2: C 67.82, H 4.79, N 8.33;
found: C 68.03, H 4.95, N 8.30%.
4.2.6. 2-{5-[2-(4-Dimethylaminophenyl)-vinyl]-furan-2-yl}-
benzothiazole (2c)
A sodium methanolate solution, prepared from sodium (50 mg,
1.9 mmol, 1.1 equiv) and dry MeOH (5 mL), was added dropwise to
a stirred suspension of phosphonium iodide 8 (1 g, 1.9 mmol,
1.1 equiv) in MeOH (5 mL) at rt. The mixture was stirred for 15 min,
a solution of aldehyde 7a (0.4 g, 1.7 mmol, 1 equiv) in MeOH (5 mL)
was added and the reaction mixture was then set to reflux for 4 h.
After cooling to ambient temperature, the solvent was evaporated,
the residue was mixed with water (20 mL) and extracted with
chloroform (3ꢂ15 mL). Combined organic layers were dried
(Na2SO4), the solvent was evaporated and the crude product was
purified by column chromatography (SiO2, hexanes/EtOAc¼4:1) to
give 0.45 g of yellow solid (E:Z isomer¼11:1, overall yield 76%). (E)-
NMR (CDCl3)
d
¼7.28 (d, 2H, J¼8.9 Hz, H2Ph, H6Ph), 6.76 (d, 2H,
J¼8.9 Hz, H3Ph, H5Ph), 6.66 (d, 1H, J¼3.0 Hz, HPYR), 6.17 (d, 1H,
J¼2.6 Hz, HPYR), 6.12 (dd, 1H, J¼3.0, 2.6 Hz, HPYR), 3.62 (s, 3H, CH3–
N
PYR), 2.98 (s, 6H, NMe2) ppm; 13C NMR (CDCl3)
d¼149.5, 134.2,
128.7, 120.1, 117.9, 112.4, 110.2, 104.8, 40.4, 34.5 ppm; IR (MeOH)
n
¼2770, 1570, 1510, 1450, 1420, 1330, 1050, 940 cmꢁ1. Anal. Calcd
for C13H16N2: C 77.96, H 8.05, N 13.99; found: C 77.74, H 8.16, N
14.10%.
isomer: mp 164–166 ꢀC; 1H NMR (CDCl3)
H
d
¼8.04 (d, 1H, J¼7.7 Hz,
BT), 7.88 (d,1H, J¼8.0 Hz, HBT), 7.48 (ddd,1H, J¼8.2, 7.1, 1.1 Hz, HBT),
7.43 (d, 2H, J¼8.8 Hz, H2Ph, H6Ph), 7.36 (ddd, 1H, J¼8.2, 8.0, 1.1 Hz,
4.2.9. 2-[2-(4-Dimethylaminophenyl)-vinyl]-furan (14a)
A solution of sodium methanolate, prepared from sodium
(0.25 g, 10.4 mmol, 1 equiv) and dry MeOH (20 mL), was added
slowly to a suspension of phosphonium iodide 8 (5.45 g, 10.4 mmol,
1 equiv) in MeOH (20 mL). The mixture was stirred for 5 min and
a solution of furan-2-carbaldehyde (1 g, 10.4 mmol, 1 equiv) in
MeOH (20 mL) was added dropwise with stirring. The mixture was
heated to reflux for 3 h, was allowed to cool and the solvent was
H
BT), 7.22 (d, 1H, J¼16.2 Hz, C]CHb), 7.21 (d, 1H, J¼3.6 Hz, H3FUR),
6.76 (d, 1H, J¼16.2 Hz, C]CHa), 6.72 (d, 2H, J¼9.1 Hz, H3Ph, H5Ph),
6.45 (d, 1H, J¼3.6 Hz, H4FUR), 3.01 (s, 6H, NMe2) ppm; 13C NMR
(CDCl3)
d¼158.0, 157.2, 154.5, 150.9, 147.5, 134.7, 131.0, 128.4, 126.8,
125.3, 125.1, 123.3, 121.9, 114.5, 112.7, 111.7, 109.7, 40.8 ppm; UV–vis

M. Zajac et al. / Tetrahedron 64 (2008) 10605–10618
10613
evaporated. The residue was mixed with hot water (200 mL) and
4.2.13. 5-(4-Dimethylaminophenyl)-thiophene-2-
carbaldehyde (10b)
the insoluble solid product was collected by filtration. The crude
product was purified by column chromatography (SiO2, hexanes/
EtOAc¼5:1) to yield 1.4 g of yellowish solid (E:Z isomer¼3.5:1,
overall yield 62%). (E)-isomer: mp 103–106 ꢀC (lit. Mp not given);36
To a solution containing the boronic acid 5 (0.57 g, 3 mmol,
1 equiv), arylbromide 9a (0.75 g, 4.5 mmol, 1.5 equiv), Pd(OAc)2
(6.7 mg, 0.03 mmol, 0.01 equiv) and PPh3 (23 mg, 0.09 mmol,
0.03 equiv), in THF (20 mL) under nitrogen, 2 M aqueous Na2CO3
solution (10 mL) was added and the mixture was heated to reflux
for 20 h. After cooling to rt, the precipitated solid was collected by
filtration. The crude product was purified by crystallization from
MeOH to give 0.63 g of yellow solid (92%). Mp 190–192 ꢀC (lit. 189–
1H NMR (CDCl3)
d
¼7.36 (d, 2H, J¼8.8 Hz, H2Ph, H6Ph), 7.35 (d,
1H, J¼2.2 Hz, H5FUR), 6.97 (d, 1H, J¼15.7 Hz, C]CH), 6.71 (d, 1H,
J¼15.7 Hz, C]CH), 6.70 (d, 2H, J¼8.8 Hz, H3Ph, H5Ph), 6.39 (dd, 1H,
J¼3.3, 2.2 Hz, H4FUR), 6.24 (d, 1H, J¼3.3 Hz, H3FUR), 2.97 (s, 6H,
NMe2) ppm.
190 ꢀC);11b 1H NMR (CDCl3)
d
¼9.82 (s, 1H, CHO), 7.68 (d, 1H,
4.2.10. 2-[2-(4-Dimethylaminophenyl)-vinyl]-thiophene (14b)
A solution of sodium methanolate, prepared from sodium
(0.34 g, 14 mmol, 1 equiv) and dry MeOH (20 mL), was added
slowly to a suspension of phosphonium iodide 8 (7.3 g, 14 mmol,
1 equiv) and MeOH (20 mL). The mixture was stirred for 15 min and
a solution of thiophene-2-carbaldehyde (1.5 g, 14 mmol, 1 equiv) in
MeOH (20 mL) was added dropwise with stirring. The mixture was
heated to reflux for 6 h, was allowed to cool and the solvent was
evaporated. The residue was mixed with hot water (200 mL) and
the insoluble solid product was collected by filtration. The crude
product was purified by column chromatography (SiO2, hexanes/
EtOAc¼4:1) to yield 2 g of yellowish solid (E:Z isomer¼3.5:1, overall
yield 63%). (E)-isomer: mp 147–149 ꢀC (146–148 ꢀC);37 1H NMR
J¼4.0 Hz, H3THP), 7.56 (d, 2H, J¼9.0 Hz, H2Ph, H6Ph), 7.24 (d, 1H,
J¼4.0 Hz, H4THP), 6.72 (d, 2H, J¼9.0 Hz, H3Ph, H5Ph), 3.03 (s, 6H,
NMe2) ppm; 13C NMR (CDCl3)
d¼182.4, 156.0, 151.0, 140.1, 138.1,
121.5, 121.4, 112.2, 40.3, 29.6 ppm. Anal. Calcd for C13H13NOS: C
67.50, H 5.66, N 6.06; found: C 67.77, H 5.68, N 6.25%.
4.2.14. 5-(4-Dimethylaminophenyl)-1-methylpyrrole-2-
carbaldehyde (10c)
To dry DMF (0.32 mL, 0.3 g, 4 mmol, 1 equiv), cooled in an ice
bath, POCl3 (0.38 mL, 0.61 g, 4 mmol, 1 equiv) was added dropwise
and the mixture was stirred for 10 min. Afterwards, a solution of 12
(0.8 g, 4 mmol; 1 equiv) in DMF (5 mL) was slowly added with
cooling, the mixture was allowed to warm up to rt and was stirred
for further 2 h. The reaction mixture was subsequently poured on
ice, neutralized with aqueous NaOH solution and the precipitate
was collected by filtration. The crude product was crystallized from
methanol to give 0.65 g of yellowish solid (72%). Mp 112–114 ꢀC; 1H
(CDCl3)
d
¼7.36 (d, 2H, J¼8.8 Hz, H2Ph, H6Ph), 7.11 (dd, 1H, J¼4.8,
1.8 Hz, H5THP), 7.04 (d, 1H, J¼16.0 Hz, C]CH), 6.98–6.96 (m, 2H,
H
3THP, H4THP), 6.86 (d, 1H, J¼16.0 Hz, C]CH), 6.70 (d, 2H, J¼8.8 Hz,
H3Ph, H5Ph), 2.98 (s, 6H, NMe2) ppm.
NMR (CDCl3)
d
¼9.52 (d, 1H, CHO), 7.30 (d, 2H, J¼9.1 Hz, H2Ph, H6Ph),
4.2.11. 2-[2-(4-Dimethylaminophenyl)-vinyl]-1-
methylpyrrole (14c)
6.96 (d, 1H, J¼4.1 Hz, H3PYR), 6.77 (d, 2H, J¼9.1 Hz, H3Ph, H5Ph), 6.24
(d, 1H, J¼3.9 Hz, H4PYR), 3.94 (s, 3H, CH3–NPYR), 3.02 (s, 6H, CH3–
To a solution of sodium methanolate, prepared from sodium
(0.22 g, 9.2 mmol, 1 equiv) and dry MeOH (10 mL), phosphonium
iodide 8 (4.8 g, 9.2 mmol, 1 equiv) was added and the mixture was
stirred for 10 min. A solution of 1-methylpyrrole-2-carbaldehyde
(1 g, 9.2 mmol, 1 equiv) in MeOH (20 mL) was added dropwise
with stirring and the mixture was heated to reflux for 8 h. After
cooling to ambient temperature, the solvent was evaporated, the
residue was mixed with water and extracted with ethyl acetate
(3ꢂ50 mL), combined organic layers were dried (Na2SO4), evapo-
rated and the residue was purified by column chromatography
(SiO2, hexanes/EtOAc¼5:1) to give 0.3 g of Z isomer as yellow oil
and 0.75 g of E isomer as yellowish solid (E:Z isomer¼2.5:1, overall
N) ppm; 13C NMR (CDCl3)
d¼179.1, 150.6, 145.6, 132.7, 130.2, 125.0,
118.5, 112.1, 110.2, 40.4, 34.6 ppm; UV–vis (CHCl3) lmax¼312 nm
(log
3
¼6.248); IR (MeOH) ¼2780, 1640, 1600, 1540, 1510, 1470,
n
1450, 1430, 1350, 1040, 920 cmꢁ1. Anal. Calcd for C14H16N2O: C
73.66, H 7.06, N 12.27; found: C 73.63, H 7.35, N 11.99%.
4.2.15. (E)-5-[2-(4-Dimethylaminophenyl)-vinyl]-furan-2-
carbaldehyde (10d)
To dry DMF (0.4 mL, 0.38 g, 5.2 mmol, 1 equiv), cooled in an ice
bath, POCl3 (0.5 mL, 0.8 g, 5.2 mmol, 1 equiv) was added dropwise.
The mixture was stirred for 10 min and a solution of 14a (1.1 g,
5.2 mmol, 1 equiv, E:Z¼4:1) in DMF (5 mL) was added with cooling.
The mixture was allowed to warm up to rt and was stirred for
further 1 h at rt and 2.5 h at 70 ꢀC. Afterwards, the mixture cooled
to ambient temperature and was poured on ice, neutralized with
aqueous NaOH and was left to stand overnight. The precipitated
solid was collected by filtration, dried and purified by column
chromatography (SiO2, hexanes/EtOAc¼5:1) to yield 0.45 g of or-
yield 50%). (E)-isomer: mp 102–104 ꢀC; 1H NMR (CDCl3)
d¼7.35 (d,
2H, J¼8.8 Hz, H2Ph, H6Ph), 6.82 (d, 1H, J¼16.0 Hz, C]CH), 6.75 (d,
1H, J¼16.0 Hz, C]CH), 6.71 (d, 2H, J¼8.8 Hz, H3Ph, H5Ph), 6.59 (m,
1H, H5PYR), 6.40 (dd, 1H, J¼3.7, 1.6 Hz, H3PYR), 6.13 (dd, 1H, J¼3.7,
2.7 Hz, H4PYR), 3.66 (s, 3H, CH3–NPYR), 2.97 (s, 6H, NMe2) ppm.
Anal. Calcd for C15H18N2: C 79.61, H 8.02, N 12.38; found: 79.37, H
8.20, N 12.10%.
ange solid (E isomer, 36%). Mp 130–131 ꢀC; 1H NMR (CDCl3)
d¼9.53
(s,1H, CHO), 7.41 (d, 2H, J¼8.8 Hz, H2Ph, H6Ph), 7.34 (d,1H, J¼16.2 Hz,
C]CH), 7.24 (d, 1H, J¼3.8 Hz, H3FUR), 6.73 (d, 1H, J¼16.2 Hz, C]CH),
6.70 (d, 2H, J¼8.8 Hz, H3Ph, H5Ph), 6.43 (d, 1H, J¼3.8 Hz, H4FUR), 3.01
4.2.12. 5-(4-Dimethylaminophenyl)-furan-2-carbaldehyde (10a)
To a solution containing the boronic acid 5 (0.25 g, 1.4 mmol,
1 equiv), arylbromide 9a (0.3 g, 1.7 mmol, 1.2 equiv), Pd(OAc)2
(3.1 mg, 0.014 mmol, 0.01 equiv) and PPh3 (11 mg, 0.042 mmol,
0.03 equiv), in THF (9 mL) under nitrogen, 2 M aqueous Na2CO3
solution (5 mL) was added and the mixture was heated to reflux for
20 h. After cooling to rt, the mixture was filtered, water was added
(20 mL), the organic layer was separated and the aqueous layer was
extracted with ethyl acetate (2ꢂ10 mL). Combined organic layers
were dried (Na2SO4), evaporated and the crude product was puri-
fied by column chromatography (SiO2, hexanes/EtOAc¼4:1) to yield
0.23 g of yellow solid (77%). Mp 96–98 ꢀC (lit. 95–98 ꢀC);35 1H NMR
(s, 6H, NMe2) ppm; 13C NMR (CDCl3)
134.2, 128.6, 124.8, 124.0, 112.3, 110.4, 109.1, 40.4 ppm; UV–vis
d
¼176.5, 160.3, 151.3, 151.0,
(CHCl3) lmax¼414 nm (log
3
¼6.06); IR (MeOH) ¼1660, 1600, 1520,
n
1480,1410,1350,1010, 920 cmꢁ1. Anal. Calcd for C15H15NO2: C 74.67,
H 6.27, N 5.80; found: C 74.84, H 6.27, N 5.74%.
4.2.16. (E)-5-[2-(4-Dimethylaminophenyl)-vinyl]-thiophene-2-
carbaldehyde (10e)
Method A. To dry DMF (0.44 mL, 0.42 g, 5.7 mmol, 1 equiv),
cooled in an ice bath, POCl3 (0.53 mL, 0.87 g, 5.7 mmol,1 equiv) was
added dropwise. The mixture was stirred for 10 min and a solution
of 14b (1.3 g, 5.7 mmol, 1 equiv, E:Z¼3.5:1) in DMF (5 mL) was
added with cooling. The mixture was allowed to warm up to rt and
(CDCl3)
d
¼9.54 (s, 1H, CHO), 7.70 (d, 2H, J¼9.2 Hz, H2Ph, H6Ph), 7.29
(d, 1H, J¼3.7 Hz, H3FUR), 6.72 (d, 2H, J¼9.2 Hz, H3Ph, H5Ph), 6.62 (d,
1H, J¼3.7 Hz, H4FUR), 2.92 (s, 6H, NMe2) ppm.

10614
M. Zajac et al. / Tetrahedron 64 (2008) 10605–10618
was stirred for further 1 h at rt and 16 h at 70 ꢀC. Afterwards, the
mixture cooled to ambient temperature and was poured on ice,
neutralized with aqueous NaOH and was left to stand overnight.
The precipitated solid was collected by filtration, dried and purified
by column chromatography (SiO2, hexanes/EtOAc¼5:1) to yield
0.22 g of red solid (E isomer, 15%).
(2 mL) were used, reaction time 3.5 h, yield 170 mg of orange
solid (54%). Mp 160–162 ꢀC; 1H NMR (CDCl3)
¼7.97 (d, 1H,
J¼8.0 Hz, HBT), 7.84 (d, 1H, J¼8.2 Hz, HBT), 7.63 (d, 2H, J¼9.1 Hz,
2Ph, H6Ph), 7.46 (ddd, 1H, J¼8.2, 7.1, 1.1 Hz, HBT), 7.34 (ddd,
BT), 7.31 (m, 2H, C]CHa, C]CHb),
d
H
1H, J¼8.0, 6.9, 1.1 Hz,
H
6.75 (d, 2H, J¼9.1 Hz, H3Ph, H5Ph), 6.63 (d, 1H, J¼3.6 Hz, HFUR),
Method B. To
a solution of 14b (0.7 g, 3 mmol, 1 equiv,
6.53 (d, 1H, J¼3.6 Hz, HFUR), 3.02 (s, 6H, NMe2) ppm; 13C NMR
E:Z¼3.5:1) in dry THF (15 mL), cooled in an ice bath, a 1.6 M solu-
tion of n-BuLi in hexanes (2.8 mL, 5.2 mmol, 1.7 equiv) was added
dropwise with stirring under an atmosphere of nitrogen. The
resulting mixture was stirred at 0 ꢀC for 1 h and subsequently dry
DMF (0.35 mL, 0.33 g, 4.5 mmol, 1.5 equiv) was added with cooling.
Afterwards, the mixture was allowed to warm to ambient tem-
perature and was stirred for further 16 h. Water was added and the
mixture was extracted with ethyl acetate (3ꢂ20 mL), combined
organic layers were washed with brine, dried (Na2SO4) and evap-
orated. The residue was crystallized from methanol to give 0.50 g of
red product (E isomer, 65%). Mp 178–181 ꢀC; 1H NMR (CDCl3)
(CDCl3)
d
¼167.2, 157.0, 154.3, 150.6, 149.9, 134.6, 126.4, 125.7,
125.1, 124.4, 122.8, 121.6, 118.7, 118.2, 116.1, 112.4, 105.5,
40.5 ppm; UV–vis (CHCl3) lmax¼436 nm (log
3
¼6.47); IR (MeOH)
n
¼1600, 1490, 1460, 1420, 1350, 1010, 910 cmꢁ1. Anal. Calcd for
C
21H18N2OS: C 72.80, H 5.24, N 8.09; found: C 72.94, H 5.32,
N 7.98%.
4.3.2. (E)-2-{2-[5-(4-Dimethylaminophenyl)-thiophen-2-yl]-
vinyl}-benzothiazole (2f)
According to GP1, aldehyde 10b (0.15 g, 0.6 mmol), 2-methyl-
benzothiazole (0.1 g, 0.7 mmol), DMSO (1.7 mL) and 50% aq KOH
(1 mL) were used, reaction time 5 h, yield 110 mg of orange solid
d
¼9.81 (s, 1H, CHO), 7.63 (d, 1H, J¼3.8 Hz, H3THP), 7.40 (d, 2H,
J¼9.1 Hz, H2Ph, H6Ph), 7.39 (d, 1H, J¼16.0 Hz, C]CH), 7.06 (d,
1H, J¼3.8 Hz, H4THP), 7.05 (d, 1H, J¼16.0 Hz, C]CH), 6.69 (d, 2H,
J¼9.1 Hz, H3Ph, H5Ph), 3.01 (s, 6H, NMe2) ppm; 13C NMR (CDCl3)
(52%). Mp 210–214 ꢀC; 1H NMR (CDCl3)
d
¼7.97 (d, 1H, J¼8.0 Hz,
H
BT), 7.84 (d, 1H, J¼7.7 Hz, HBT), 7.62 (d, 1H, J¼15.7 Hz, C]CHb),
7.52 (d, 2H, J¼8.8 Hz, H2Ph, H6Ph), 7.46 (ddd, 1H, J¼8.0, 7.1,
0.8 Hz, HBT), 7.35 (ddd, 1H, J¼8.0, 6.9, 1.1 Hz, HBT), 7.16 (d, 1H,
J¼3.8 Hz, HTHP), 7.12 (d, 1H, J¼15.7 Hz, C]CHa), 7.11 (d, 1H,
J¼3.8 Hz, HTHP), 6.73 (d, 2H, J¼8.8 Hz, H3Ph, H5Ph), 3.01 (s, 6H,
d
¼181.3, 155.6, 148.7, 140.1, 137.3, 132.1, 129.2, 124.5, 122.1, 112.6,
110.5, 40.5 ppm; UV–vis (MeOH) lmax¼418 nm (log ¼6.37). Anal.
3
Calcd for C15H15NOS: C 70.01, H 5.87, N 5.44; found: C 69.85, H 5.94,
N 5.34%.
NMe2) ppm; 13C NMR (CDCl3)
d¼167.0, 154.2, 150.6, 147.8, 138.0,
134.5, 131.3, 130.9, 127.1, 126.5, 125.2, 122.9, 122.2, 121.7, 121.6,
4.2.17. (E)-5-[2-(4-Dimethylaminophenyl)-vinyl]-1-methyl-
pyrrole-2-carbaldehyde (10f)
119.7, 112.5, 40.6 ppm; UV–vis (MeOH) lmax¼430 (log ¼6.46); IR
3
(MeOH)
n
¼1600, 1510, 1470, 1440, 1420, 1040, 920 cmꢁ1. Anal.
To dry DMF (0.4 mL, 0.37 g, 5.0 mmol, 1 equiv), cooled in an ice
bath, POCl3 (0.47 mL, 0.77 g, 5.0 mmol, 1 equiv) was added drop-
wise. The mixture was stirred for 10 min, dry 1,2-dichloroethane
was added and subsequently a solution of 14c (1.14 g, 5.0 mmol,
1 equiv, E isomer) in 1,2-dichloroethane (5 mL) was added drop-
wise with cooling. The mixture was allowed to warm up to ambient
temperature and was stirred for 10 min. Afterwards the mixture
was heated to reflux for 30 min, cooled to rt and saturated aqueous
solution of sodium acetate was added. The mixture was extracted
with CHCl3 (3ꢂ20 mL), combined organic layers were washed with
brine, dried (Na2SO4) and evaporated. The crude product was pu-
rified by column chromatography (SiO2, hexanes/EtOAc¼4:1) to
yield 0.25 g of yellow solid (20%, E isomer). Mp 146–150 ꢀC; 1H NMR
Calcd for C21H18N2S2: C 69.58, H 5.00, N 7.73; found: C 69.15,
H 4.90, N 7.38%.
4.3.3. (E)-2-{2-[5-(4-Dimethylaminophenyl)-1-methylpyrrol-2-yl]-
vinyl}-benzothiazole (2g)
According to GP1, aldehyde 10c (0.1 g, 0.43 mmol), 2-methyl-
benzothiazole (71 mg, 0.47 mmol), DMSO (2 mL) and 50% aq KOH
(1 mL) were used, reaction time 16 h, yield 95 mg of yellow solid
(43%). Mp 174–176 ꢀC; 1H NMR (CDCl3)
d
¼7.93 (d, 1H, J¼8.0 Hz,
H
BT), 7.82 (d, 1H, J¼8.0 Hz, HBT), 7.50 (d, 1H, J¼15.7 Hz, C]CHb),
7.44 (ddd, 1H, J¼8.0, 7.4, 1.1 Hz, HBT), 7.32 (ddd, 1H, J¼8.0, 7.4,
1.1 Hz, HBT), 7.29 (d, 2H, J¼8.8 Hz, H2Ph, H6Ph), 7.12 (d, 1H,
J¼15.7 Hz, C]CHa), 6.78 (d, 2H, J¼8.8 Hz, H3Ph, H5Ph), 6.76 (d,
1H, J¼4.1 Hz, H3PYR), 6.24 (d, 1H, J¼3.8 Hz, H4PYR), 3.73 (s, 3H,
(CDCl3)
d
¼9.44 (s, 1H, CHO), 7.40 (d, 2H, J¼8.8 Hz, H2Ph, H6Ph), 7.07
(d, 1H, J¼16.2 Hz, C]CH), 6.90 (d, 1H, J¼4.4 Hz, H3PYR), 6.77 (d, 1H,
J¼15.9 Hz, C]CH), 6.71 (d, 2H, J¼8.8 Hz, H3Ph, H5Ph), 6.50 (d, 1H,
CH3–NPYR), 3.01 (s, 6H, NMe2) ppm; 13C NMR (CDCl3)
d¼168.1,
154.3, 150.1, 140.2, 134.3, 131.2, 130.2, 126.4, 126.4, 124.8, 122.5,
121.5, 120.5, 116.7, 112.4, 111.2, 109.9, 40.6, 32.7 ppm; UV–vis
J¼4.1 Hz, H4PYR), 3.01 (s, 3H, CH3–NPYR), 3.01 (s, 6H, NMe2) ppm; 13
C
NMR (CDCl3)
d
¼178.6, 150.8, 143.2, 133.9, 132.2, 130.1, 128.1, 124.9,
(CHCl3) lmax¼416 nm (log
3
¼6.45), 550 nm (log ¼5.86); IR
3
112.4, 110.4, 107.3, 40.5, 32.6 ppm; UV–vis (CHCl3) lmax¼342 nm
(MeOH)
n
¼1610, 1540, 1520, 1450, 1440, 1420, 1050, 920 cmꢁ1
.
(log
3
¼6.21); IR (MeOH)
n
¼1660, 1600, 1520, 1480, 1410, 1360,
Anal. Calcd for C22H21N3S: C 73.50, H 5.89, N 11.69; found: C 73.55,
H 5.83, N 11.40%.
920 cmꢁ1. Anal. Calcd for C16H18N2O: C 75.56, H 7.14, N 11.01;
found: C 75.72, H 7.05, N 10.78%.
4.3.4. (E,E)-2-(2-{5-[2-(4-Dimethylaminophenyl)-vinyl]-furan-2-
yl}-vinyl)-benzothiazole (2h)
4.3. GP1: condensation reactions of 2-methylbenzothiazole15c
According to GP1, aldehyde 10d (0.1 g, 0.41 mmol), 2-methyl-
benzothiazole (69 mg, 0.46 mmol), DMSO (2 mL) and 50% aq KOH
(1 mL) were used, reaction time 6 h, yield 140 mg of red solid (92%).
To a solution of the corresponding aldehyde (1 equiv) and
2-methylbenzothiazole (1.1 equiv) in DMSO, 50% aqueous solution
of KOH was added, the mixture was stirred for 10 min and after-
wards left at rt without stirring for the given time. The precipitate
was collected by filtration, washed with water (50 mL) and cold
methanol (5 mL) and dried in vacuum to yield the product in good
purity.
Mp 192–195 ꢀC; 1H NMR (CDCl3)
d¼7.97 (d, 1H, J¼7.7 Hz, HBT), 7.84
(d, 1H, J¼8.0 Hz, HBT), 7.46 (ddd, 1H, J¼8.5, 7.1, 1.4 Hz, HBT), 7.41 (d,
2H, J¼8.8 Hz, H2Ph, H6Ph), 7.36 (d, 1H, J¼15.7 Hz, C]CHb), 7.35 (ddd,
1H, J¼8.0, 6.9, 1.4 Hz, HBT), 7.27 (d, 1H, J¼15.9 Hz, C]CHa), 7.15
(d, 1H, J¼16.2 Hz, C]CHd), 6.72 (d, 2H, J¼8.8 Hz, H3Ph, H5Ph), 6.70
(d, 1H, J¼16.2 Hz, C]CHg), 6.59 (d, 1H, J¼3.6 Hz, H3FUR), 6.33 (d, 1H,
4.3.1. (E)-2-{2-[5-(4-Dimethylaminophenyl)-furan-2-yl]-vinyl}-
benzothiazole (2e)
According to GP1, aldehyde 10a (0.2 g, 0.9 mmol), 2-methyl-
benzothiazole (0.15 g, 1.0 mmol), DMSO (5 mL) and 50% aq KOH
J¼3.6 Hz,
H4FUR), 3.01 (s, 6H, NMe2) ppm; UV–vis (CHCl3)
lmax¼448 nm (log
3
¼6.56); IR (MeOH) ¼1610, 1520, 1420, 1010,
n
920 cmꢁ1. Anal. Calcd for C23H20N2OS: C 74.16, H 5.41, N 7.52;
found: C 73.77, H 5.29, N 7.15%.

M. Zajac et al. / Tetrahedron 64 (2008) 10605–10618
10615
4.3.5. (E,E)-2-(2-{5-[2-(4-Dimethylaminophenyl)-vinyl]-thiophen-
4.4.2. (E)-2-{2-[5-(4-Dimethylaminophenyl)-furan-2-yl]-vinyl}-3-
2-yl}-vinyl)-benzothiazole (2i)
(prop-2-enyl)-benzothiazolium bromide (3aA)
According to GP1, aldehyde 10e (0.1 g, 0.39 mmol), 2-methyl-
benzothiazole (64 mg, 0.43 mmol), DMSO (2 mL) and 50% aq
KOH (1 mL) were used, reaction time 16 h, yield 120 mg of or-
According to GP2, aldehyde 10a (0.15 g, 0.7 mmol), 3-allyl-2-
methylbenzothiazolium bromide (0.19 g, 0.7 mmol) and MeOH
(3 mL) were used, reaction time 14 h, yield 140 mg of dark green
ange solid (79%). Mp 209–211 ꢀC; 1H NMR (CDCl3)
d
¼7.97 (d, 1H,
solid (43%). Mp 165 ꢀC (decomp.); 1H NMR (DMSO-d6)
d¼8.37 (d,1H,
J¼7.6 Hz, HBT), 7.84 (d, 1H, J¼8.4 Hz, HBT), 7.60 (d, 1H, J¼15.7 Hz,
C]CHb), 7.46 (ddd, 1H, J¼8.4, 7.3, 1.2 Hz, HBT), 7.39 (d, 2H,
J¼8.6 Hz, H2Ph, H6Ph), 7.35 (ddd, 1H, J¼8.4, 7.3, 1.2 Hz, HBT), 7.12
(d, 1H, J¼15.7 Hz, C]CHa), 7.11 (d, 1H, J¼3.8 Hz, H3THP), 7.00 (d,
1H, J¼16.0 Hz, C]CHd), 6.92 (d, 1H, J¼3.8 Hz, H4THP), 6.91 (d, 1H,
J¼16.0 Hz, C]CHg), 6.70 (d, 2H, J¼8.7 Hz, H3Ph, H5Ph), 3.00 (s,
J¼8.0 Hz, H7BT), 8.13 (d, 1H, J¼8.2 Hz, H4BT), 8.06 (d, 1H, J¼15.1 Hz,
C]CHb), 7.88 (d, 2H, J¼9.1 Hz, H2Ph, H6Ph), 7.80 (t,1H, J¼8.2 Hz, H5BT),
7.71 (t, 1H, J¼7.7 Hz, H6BT), 7.52 (d, 1H, J¼3.8 Hz, H3FUR), 7.46 (d, 1H,
J¼15.1 Hz, C]CHa), 7.17 (d, 1H, J¼3.8 Hz, H4FUR), 6.83 (d, 2H,
J¼9.1 Hz, H3Ph, H5Ph), 6.18–6.04 (m,1H, C]CH), 5.57 (d, 2H, J¼4.9 Hz,
CH2), 5.37 (d,1H, J¼10.7 Hz, C]CH2), 5.30 (d,1H, J¼17.3 Hz, C]CH2),
6H, NMe2) ppm; UV–vis (CHCl3) lmax¼452 nm (log
3¼6.55); IR
3.04 (s, 6H, NMe2) ppm; 13C NMR (DMSO-d6)
d¼170.4, 161.4, 151.2,
(MeOH)
n
¼1600, 1520, 1420, 1350 cmꢁ1
.
Anal. Calcd for
149.1, 141.0, 133.2, 130.6, 129.0,127.6, 127.2, 126.9, 126.8, 124.1, 118.9,
116.0, 115.5, 111.8, 108.3, 105.8, 50.0, 39.6 ppm; UV–vis (MeOH)
C
23H20N2S2: C 71.10, H 5.19, N 7.21; found: C 70.85, H 5.20, N
6.95%.
lmax¼596 nm (log
3
¼6.68); IR (ATR) ¼2900,1593,1497, 1408,1369,
n
1235, 1193, 1031, 942 cmꢁ1. Anal. Calcd for C24H23BrN2OS: C 61.67, H
4.96, N 5.99; found: C 61.36, H 5.11, N 5.87%.
4.3.6. (E,E)-2-(2-{5-[2-(4-Dimethylaminophenyl)-vinyl]-1-
methylpyrrol-2-yl}-vinyl)-benzothiazole (2j)
According to GP1, aldehyde 10f (0.1 g, 0.39 mmol), 2-methyl-
benzothiazole (65 mg, 0.43 mmol), DMSO (2 mL) and 50% aq
KOH (1 mL) were used, reaction time 16 h, yield 70 mg of red
4.4.3. (E)-2-{2-[5-(4-Dimethylaminophenyl)-furan-2-yl]-vinyl}-3-
(prop-2-ynyl)-benzothiazolium bromide (3aP)
According to GP2, aldehyde 10a (0.15 g, 0.7 mmol), 2-methyl-3-
(prop-2-ynyl)-benzothiazolium bromide (0.17 g, 0.7 mmol) and
MeOH (5 mL) were used, reaction time 16 h, yield 100 mg of dark
solid (46%). Mp 202–205 ꢀC; 1H NMR (CDCl3)
d¼7.93 (d, 1H,
J¼8.0 Hz, HBT), 7.82 (d, 1H, J¼8.0 Hz, HBT), 7.47 (d, 1H, J¼15.7 Hz,
C]CHb), 7.44 (ddd, 1H, J¼8.2, 7.1, 1.4 Hz, HBT), 7.38 (d, 2H,
J¼8.8 Hz, H2Ph, H6Ph), 7.31 (ddd, 1H, J¼8.2, 7.1, 1.4 Hz, HBT), 7.09 (d,
1H, J¼15.7 Hz, C]CHa), 6.93 (d, 1H, J¼15.9 Hz, C]CHd), 6.79 (d, 1H,
J¼15.9 Hz, C]CHg), 6.75 (d, 1H, J¼4.1 Hz, H3PYR), 6.71 (d, 2H,
J¼8.8 Hz, H3Ph, H5Ph), 6.54 (d, 1H, J¼4.1 Hz, H4PYR), 3.76 (s, 3H,
green solid (31%). Mp 177 ꢀC (decomp.); 1H NMR (DMSO-d6)
d
¼8.37
(d, 1H, J¼8.0 Hz, H7BT), 8.20 (d, 1H, J¼8.8 Hz, H4BT), 8.10 (d, 1H,
J¼15.1 Hz, C]CHb), 7.91 (d, 2H, J¼8.8 Hz, H2Ph, H6Ph), 7.85 (t, 1H,
J¼8.2 Hz, H5BT), 7.73 (t, 1H, J¼8.0 Hz, H6BT), 7.58 (d, 1H, J¼15.1 Hz,
C]CHa), 7.57 (d, 1H, J¼3.8 Hz, H3FUR), 7.21 (d, 1H, J¼4.1 Hz, H4FUR),
6.85 (d, 2H, J¼9.1 Hz, H3Ph, H5Ph), 5.86 (d, 2H, J¼2.2 Hz, CH2), 3.78
(m, 1H, C^CH), 3.05 (s, 6H, NMe2) ppm; 13C NMR (DMSO-d6)
CH3–NPYR), 3.00 (s, 6H, NMe2) ppm; 13C NMR (CDCl3)
154.3, 150.3, 137.7, 134.3, 131.2, 129.5, 127.6, 126.4, 125.9, 125.4,
124.8, 122.4, 121.5, 116.7, 112.7, 112.3, 111.8, 107.8, 40.7, 31.0 ppm;
d
¼167.9,
d
¼171.4, 163.0, 152.3, 150.2, 141.4, 134.6, 130.1, 128.7, 128.8, 128.1,
UV–vis (CHCl3) lmax¼464 nm (log
3
¼6.52); IR (MeOH) ¼1600,
n
127.9, 125.2, 116.7, 116.3, 112.8, 109.7, 106.2, 79.3, 76.9, 40.6,
1520, 1420, 920 cmꢁ1. Anal. Calcd for C24H23N3S: C 74.77, H
6.01, N 10.90; found: C 74.85, H 6.24, N 10.54%.
38.7 ppm; UV–vis (MeOH) lmax¼612 nm (log ¼6.64); IR (ATR)
3
n
¼2901, 1590, 1529, 1494, 1407, 1371, 1335, 1184, 1016, 943 cmꢁ1
.
Anal. Calcd for C24H21BrN2OS: C 61.94, H 4.55, N 6.02; found: C
62.05, H 4.94, N 5.85%.
4.4. GP2: condensation reactions of 3-alkyl-2-methyl-
benzothiazolium salts15c
4.4.4. (E)-2-{2-[5-(4-Dimethylaminophenyl)-thiophen-2-yl]-
vinyl}-3-methylbenzothiazolium iodide (3bM)
To a solution of the corresponding aldehyde (1 equiv) and the
corresponding 2-methyl-3-alkylbenzothiazolium salt (1 equiv) in
dry MeOH, a few drops of pyridine were added and the mixture was
heated to reflux for the given time. Afterwards, the mixture
was cooled to ꢁ10 ꢀC in the refrigerator and the crystallized solid
was collected by filtration, washed with cold MeOH and dried in
vacuum to give the product in good purity.
According to GP2, aldehyde 10b (0.2 g, 0.8 mmol), 2,3-dime-
thylbenzothiazolium iodide (0.32 g, 1.2 mmol) and MeOH (5 mL)
were used, reaction time 35 h, yield 160 mg of dark green solid
(40%). Mp 214 ꢀC (decomp.); 1H NMR (DMSO-d6)
d
¼8.39 (d, 1H,
J¼15.4 Hz, C]CHb), 8.37 (d, 1H, J¼7.1 Hz, H7BT), 8.17 (d, 1H,
J¼8.2 Hz, H4BT), 7.90 (d, 1H, J¼3.8 Hz, H3THP), 7.83 (t, 1H, J¼8.0 Hz,
H
5BT), 7.74 (t, 1H, J¼7.1 Hz, H6BT), 7.63 (d, 2H, J¼8.8 Hz, H2Ph, H6Ph),
7.58 (d,1H, J¼3.8 Hz, H4THP), 7.48 (d, 1H, J¼15.1 Hz, C]CHa), 6.79 (d,
2H, J¼8.8 Hz, H3Ph, H5Ph), 4.27 (s, 3H, CH3–NBT), 3.00 (s, 6H,
4.4.1. (E)-2-{2-[5-(4-Dimethylaminophenyl)-furan-2-yl]-vinyl-1-
yl}-3-methylbenzothiazolium iodide (3aM)
According to GP2, aldehyde 10a (0.11 g, 0.5 mmol), 2,3-dime-
thylbenzothiazolium iodide (0.15 g, 0.5 mmol) and MeOH (5 mL)
were used, reaction time 14 h, yield 140 mg of dark green solid
NMe2) ppm; 13C NMR (DMSO-d6)
d
¼171.5, 154.8, 153.8, 142.7, 142.0,
139.4, 136.7, 128.0, 128.7, 128.1, 128.0, 124.9, 124.1, 120.7, 117.2, 113.1,
110.0, 36.9 ppm (the CH3–N signal is overlapped with the DMSO
signal); UV–vis (MeOH) lmax¼562 nm (log ¼6.54); IR (ATR)
3
(58%). Mp¼160 ꢀC (decomp.); 1H NMR (DMSO-d6)
d
¼8.35 (d, 1H,
n
¼2988, 2901, 1571, 1430, 1411, 1361, 1347, 1275, 1190, 1064,
J¼8.1 Hz, H7BT), 8.16 (d, 1H, J¼8.4 Hz, H4BT), 8.01 (d, 1H, J¼15.2 Hz,
C]CHb), 7.88 (d, 2H, J¼9.0 Hz, H2Ph, H6Ph), 7.82 (t, 1H, J¼8.4 Hz,
956 cmꢁ1. Anal. Calcd for C22H21IN2S2: C 52.38, H 4.20, N 5.55;
found: C 52.19, H 4.35, N 5.39%.
H
5BT), 7.71 (t, 1H, J¼8.1 Hz, H6BT), 7.50 (d, 1H, J¼15.2 Hz, C]CHa),
7.48 (d, 1H, J¼3.8 Hz, H3FUR), 7.15 (d, 1H, J¼3.8 Hz, H4FUR), 6.81 (d,
4.4.5. (E)-2-{2-[5-(4-Dimethylaminophenyl)-thiophen-2-yl]-
vinyl}-3-(prop-2-enyl)-benzothiazolium bromide (3bA)
2H, J¼9.2 Hz, H3Ph, H5Ph), 4.29 (s, 3H, CH3–NBT), 3.03 (s, 6H,
NMe2) ppm; 13C NMR (DMSO-d6)
d
¼176.4, 161.1, 151.3, 149.2, 142.0,
According to GP2, aldehyde 10b (0.2 g, 0.8 mmol), 3-allyl-2-
methylbenzothiazolium bromide (0.25 g, 0.9 mmol) and MeOH
(5 mL) were used, reaction time 24 h, yield 230 mg of dark green
132.8,129.1,127.1, 126.9,126.4,124.0,116.2, 115.8,112.0,108.2,106.6,
105.6, 35.8 ppm (the CH3–N signal is overlapped with the DMSO
signal); UV–vis (MeOH) lmax¼582 nm (log
3
¼6.64); IR (ATR)
solid (60%). Mp 254 ꢀC (decomp.); 1H NMR (CD3OD)
d
¼8.36 (d, 1H,
n
¼2987, 2900, 1591, 1535, 1497, 1462, 1431, 1398, 1369, 1222, 1191,
J¼15.1 Hz, C]CHb), 8.18 (d, 1H, J¼8.0 Hz, H7BT), 8.04 (d, 1H,
1028, 914 cmꢁ1. Anal. Calcd for C22H21IN2OS: C 54.10, H 4.33, N 5.74;
found: C 54.00, H 4.65, N 5.57%.
J¼8.2 Hz, H4BT), 7.81 (t, 1H, J¼8.0 Hz, H5BT), 7.74 (d, 1H, J¼3.8 Hz,
H3THP), 7.72 (t, 1H, J¼8.2 Hz, H6BT), 7.65 (d, 2H, J¼8.8 Hz, H2Ph, H6Ph),

10616
M. Zajac et al. / Tetrahedron 64 (2008) 10605–10618
7.45 (d, 1H, J¼4.1 Hz, H4THP), 7.31 (d, 1H, J¼14.9 Hz, C]CHa), 6.80 (d,
2H J¼9.1 Hz, H3Ph, H5Ph), 6.21–6.09 (m, 1H, C]CH), 5.47 (d, 2H,
J¼5.2 Hz, CH2), 5.44 (d, 1H, J¼10.7 Hz, C]CH2), 5.24 (d, 1H,
J¼17.3 Hz, C]CH2), 3.05 (s, 6H, NMe2) ppm; satisfactory 13C NMR
was not obtained due to very low solubility; UV–vis (MeOH)
4.4.9. (E,E)-2-(2-{5-[2-(4-Dimethylaminophenyl)-vinyl]-furan-2-
yl}-vinyl)-3-methylbenzothiazolium iodide (3dM)
According to GP2, aldehyde 10d (0.15 g, 0.6 mmol), 2,3-dime-
thylbenzothiazolium iodide (0.17 g, 0.6 mmol) and MeOH (3 mL)
were used, reaction time 16 h, yield 260 mg of dark green solid
lmax¼580 nm (log
3
¼6.70); IR (ATR)
n
¼2905, 1583, 1485, 1405,
(84%). Mp 237 ꢀC (decomp.); 1H NMR (CD3OD)
d
¼8.15 (d, 1H,
1365, 1229,1071, 947 cmꢁ1. Anal. Calcd for C24H23BrN2S2: C 59.62, H
4.79, N 5.79; found: C 59.75, H 4.77, N 5.78%.
J¼7.4 Hz, H7BT), 8.06 (d, 1H, J¼8.5 Hz, H4BT), 7.90 (d, 1H, J¼15.1 Hz,
C]CHb), 7.82 (t, 1H, J¼8.5 Hz, H5BT), 7.72 (t, 1H, J¼7.7 Hz, H6BT), 7.48
(d, 1H, J¼16.2 Hz, C]CHd), 7.47 (d, 1H, J¼15.1 Hz, C]CHa), 7.46 (d,
2H, J¼8.0 Hz, H2Ph, H6Ph), 7.29 (d, 1H, J¼3.6 Hz, H3FUR), 6.89 (d, 1H,
J¼16.2 Hz, C]CHg), 6.74 (d, 2H, J¼8.8 Hz, H3Ph, H5Ph), 6.69 (d, 1H,
4.4.6. (E)-2-{2-[5-(4-Dimethylaminophenyl)-1-methylpyrrol-2-
yl]vinyl}-3-methylbenzothiazolium iodide (3cM)
According to GP2, aldehyde 10c (0.2 g, 0.88 mmol), 2,3-dime-
thylbenzothiazolium iodide (0.26 g, 0.88 mmol) and MeOH (3 mL)
were used, reaction time 16 h, yield 190 mg of dark green solid
J¼3.8 Hz, H4FUR), 4.29 (s, 3H, CH3–NBT), 3.00 (s, 6H, NMe2) ppm; 13
C
NMR (CD3OD)
d
¼172.2, 163.3, 152.7, 151.5, 150.1, 143.6, 136.0, 134.1,
130.6, 129.9, 129.3, 128.8, 125.6, 125.4, 124.6, 116. 9, 113.2, 111.0,
(43%). Mp 254 ꢀC (decomp.); 1H NMR (CD3OD)
d
¼8.04 (d, 1H,
107.5, 40.3, 36.2 ppm; UV–vis (MeOH) lmax¼592 nm (log ¼6.61).
3
J¼7.7 Hz, H7BT), 7.99 (d, 1H, J¼15.1 Hz, C]CHb), 7.92 (d, 1H,
Anal. Calcd for C24H23IN2OS: C 56.34, H 4.51, N 5.45; found: C 56.58,
H 4.76, N 5.40%.
J¼8.5 Hz, H4BT), 7.74 (t, 1H, J¼8.5 Hz, H5BT), 7.62 (t, 1H, J¼7.7 Hz,
H
6BT), 7.54 (d,1H, J¼4.6 Hz, H3PYR), 7.41 (d, 2H, J¼8.8 Hz, H2Ph, H6Ph),
7.33 (d, 1H, J¼14.6 Hz, C]CHa), 6.87 (d, 2H, J¼9.0 Hz, H3Ph, H5Ph),
6.55 (d, 1H, J¼3.8 Hz, H4PYR), 4.15 (s, 3H, CH3–NBT), 3.88 (s, 3H, CH3–
4.4.10. (E,E)-2-(2-{5-[2-(4-Dimethylaminophenyl)-vinyl]-furan-2-
yl}-vinyl)-3-(prop-2-enyl)-benzothiazolium bromide (3dA)
N
PYR), 3.04 (s, 6H, NMe2) ppm; 13C NMR (DMSO-d6)
d
¼169.8, 150.4,
According to GP2, aldehyde 10d (0.15 g, 0.6 mmol), 3-allyl-2-
methylbenzothiazolium bromide (0.16 g, 0.6 mmol) and MeOH
(3 mL) were used, reaction time 12 h, yield 90 mg of dark red solid
146.1, 141.9, 136.0, 132.3, 129.8, 128.7, 127.0, 126.4, 123.6, 119.8, 117.4,
115.5, 113.5, 112.0, 104.0, 35.2, 32.6 ppm (the CH3–N signal is
overlapped with the DMSO signal); UV–vis (MeOH) lmax¼560 nm
(30%). Mp 218 ꢀC (decomp.); 1H NMR (DMSO-d6)
d
¼8.39 (d, 1H,
(log
3
¼6.79); IR (ATR)
n
¼2970, 1566, 1435, 1365, 1229, 1201, 1070,
J¼8.0 Hz, H7BT), 8.15 (d, 1H, J¼8.2 Hz, H4BT), 8.06 (d, 1H, J¼15.1 Hz,
C]CHb), 7.82 (t,1H, J¼8.0 Hz, H5BT), 7.73 (t,1H, J¼8.2 Hz, H6BT), 7.53–
7.43 (m, 5H, H2Ph, H6Ph, H3FUR, C]CHa, C]CHd), 7.00 (d, 1H,
J¼16.2 Hz, C]CHg), 6.85 (d, 1H, J¼3.6 Hz, H4FUR), 6.76 (d, 2H,
J¼9.1 Hz, H3Ph, H5Ph), 6.17–6.05 (m,1H, C]CH), 5.57 (d, 2H, J¼4.7 Hz,
CH2), 5.37 (d,1H, J¼10.4 Hz, C]CH2), 5.30 (d,1H, J¼17.6 Hz, C]CH2),
3.00 (s, 6H, NMe2) ppm; satisfactory 13C NMR was not obtained due
1019, 919 cmꢁ1. Anal. Calcd for C23H24IN3S: C 55.09, H 4.82, N 8.38;
found: C 55.39, H 4.98, N 8.47%.
4.4.7. (E)-2-{2-[5-(4-Dimethylaminophenyl)-1-methylpyrrol-2-yl]-
vinyl}-3-(prop-2-enyl)-benzothiazolium bromide (3cA)
According to GP2, aldehyde 10c (0.2 g, 0.88 mmol), 3-allyl-2-
methylbenzothiazolium bromide, (0.24 g, 0.88 mmol) and MeOH
(3 mL) were used, reaction time 17 h, yield 180 mg of dark blue
to very lowsolubility; UV–vis (MeOH) lmax¼606 nm (log ¼6.56); IR
3
(ATR)
n
¼2988, 2900, 1575, 1525, 1462, 1414, 1363, 1239, 1159, 1026,
solid (43%). Mp 246 ꢀC (decomp.); 1H NMR (CD3OD)
d¼8.06 (d, 1H,
943 cmꢁ1. Anal. Calcd for C26H25BrN2OS: C 63.28, H 5.11, N 5.68;
found: C 62.97, H 5.32, N 5.51%.
J¼8.0 Hz, H7BT), 7.99 (d, 1H, J¼14.6 Hz, C]CHb), 7.86 (d, 1H,
J¼8.2 Hz, H4BT), 7.71 (ddd, 1H, J¼8.5, 7.4, 1.1 Hz, H5BT), 7.60 (ddd,
1H, J¼8.5, 7.4, 1.1 Hz, H6BT), 7.54 (d, 1H, J¼4.4 Hz, H3PYR), 7.42 (d, 2H,
J¼8.8 Hz, H2Ph, H6Ph), 7.24 (d, 1H, J¼14.6 Hz, C]CHa), 6.86 (d,
2H, J¼8.8 Hz, H3Ph, H5Ph), 6.57 (d, 1H, J¼4.6 Hz, H4PYR), 6.17–6.06 (m,
1H, C]CH), 5.39 (d, 1H, J¼10.4 Hz, C]CH2), 5.33 (d, 2H, J¼4.9 Hz,
CH2), 5.20 (d, 1H, J¼17.0 Hz, C]CH2), 3.88 (s, 3H, CH3–NPYR), 3.04 (s,
4.4.11. (E,E)-2-(2-{5-[2-(4-Dimethylaminophenyl)-vinyl]-thiophen-
2-yl}-vinyl)-3-(prop-2-enyl)-benzothiazolium bromide (3eA)
According to GP2, aldehyde 10e (0.15 g, 0.58 mmol), 3-allyl-2-
methylbenzothiazolium bromide (0.24 g, 0.58 mmol) and MeOH
(4 mL) were used, reaction time 20 h, yield 160 mg of dark green
6H, NMe2) ppm; 13C NMR (CD3OD)
134.3, 131.3, 131.0, 130.2, 130.0, 128.4, 127.9, 124.4, 122.5, 119.4,
119.0, 116.1, 115.7, 113.3, 103.2, 35.2, 40.4, 33.2 ppm; UV–vis (MeOH)
d
¼171.5, 152.6, 142.7, 137.8,
solid (54%). Mp 210 ꢀC (decomp.); 1H NMR (DMSO-d6)
d
¼8.44 (d,
1H, J¼15.1 Hz, C]CHb), 8.40 (d, 1H, J¼7.7 Hz, H7BT), 8.16 (d, 1H,
J¼8.5 Hz, H4BT), 7.88 (d, 1H, J¼3.8 Hz, H3THP), 7.83 (t, 1H, J¼8.2 Hz,
H5BT), 7.74 (t, 1H, J¼8.0 Hz, H6BT), 7.50 (d, 2H, J¼9.1 Hz, H2Ph, H6Ph),
7.45 (d, 1H, J¼15.1 Hz, C]CHa), 7.33 (d, 1H, J¼4.1 Hz, H4THP), 7.31 (d,
1H, J¼15.9 Hz, C]CHd), 7.15 (d, 1H, J¼15.9 Hz, C]CHg), 6.75
(d, 2H, J¼8.8 Hz, H3Ph, H5Ph), 6.16–6.03 (m, 1H, C]CH), 5.56 (d, 2H,
J¼4.4 Hz, CH2), 5.35 (d, 1H, J¼10.4 Hz, C]CH2), 5.26 (d, 1H,
J¼17.0 Hz, C]CH2), 2.98 (s, 6H, NMe2) ppm; 13C NMR (DMSO-d6)
lmax¼570 nm (log
3
¼6.81); IR (ATR) ¼2970, 2886,1576,1474, 1350,
n
1263, 1183, 1058, 943 cmꢁ1. Anal. Calcd for C25H26BrN3S: C 62.50, H
5.45, N 8.75; found: C 62.89, H 5.62, N 8.87%.
4.4.8. (E)-2-{2-[5-(4-Dimethylaminophenyl)-1-methylpyrrol-2-yl]-
vinyl}-3-(prop-2-ynyl)-benzothiazolium bromide (3cP)
According to GP2, aldehyde 10c (0.2 g, 0.88 mmol), 2-methyl-3-
(prop-2-ynyl)-benzothiazolium bromide, (0.24 g, 0.88 mmol) and
MeOH (3 mL) were used, reaction time 16 h, yield 270 mg of dark
d
¼170.8, 153.1, 150.5, 141.6, 140.9, 138.0, 136.4, 133.4, 130.5, 129.2,
128.4, 127.9, 127.8, 127.5, 127.1, 124.1, 123.4, 118.8, 116.2, 112.0, 109.2,
50.2 ppm (the CH3–N signal is overlapped with the DMSO signal);
green solid (64%). Mp 240 ꢀC (decomp.); 1H NMR (CD3OD)
d¼8.03 (d,
UV–vis (MeOH) lmax¼590 nm (log
3
¼6.60); IR (ATR) ¼2987, 2900,
n
1H, J¼8.8 Hz, H7BT), 8.00 (d, 1H, J¼14.3 Hz, C]CHb), 7.94 (d, 1H,
1564, 1521, 1407, 1353, 1242, 1159, 1048, 941, 805 cmꢁ1. Anal. Calcd
for C26H25BrN2S2: C 61.29, H 4.95, N 5.50; found: C 61.56, H 5.01, N
5.37%.
J¼8.2 Hz, H4BT), 7.73 (t, 1H, J¼8.5 Hz, H5BT), 7.62 (d, 1H, J¼4.7 Hz,
H
3PYR), 7.60 (t, 1H, J¼8.2 Hz, H6BT), 7.43 (d, 2H, J¼8.8 Hz, H2Ph, H6Ph),
7.36 (d,1H, J¼14.3 Hz, C]CHa), 6.86 (d, 2H, J¼9.0 Hz, H3Ph, H5Ph), 6.62
(d, 1H, J¼4.7 Hz, H4PYR), 5.54 (d, 2H, J¼2.5 Hz, CH2), 3.90 (s, 3H, CH3–
4.4.12. (E,E)-2-(2-{5-[2-(4-Dimethylaminophenyl)-vinyl]-1-
methylpyrrol-2-yl}-vinyl)-3-(prop-2-enyl)-benzothiazolium
bromide (3fA)
N
PYR), 3.15 (m,1H, C^CH), 3.04 (s, 6H, NMe2) ppm; 13C NMR (DMSO-
d6)
d
¼169.9, 151.1, 148.0, 140.9, 137.6, 133.5, 130.5, 129.3, 127.5, 126.7,
124.3, 121.7, 117.5, 115.5, 115.0, 112.5, 103.3, 78.3, 76.8, 37.5, 40.6 ppm
(the CH3–N signal is overlapped with the DMSO signal); UV–vis
According to GP2, aldehyde 10f (0.1 g, 0.4 mmol), 3-allyl-2-
methylbenzothiazolium bromide (0.11 g, 0.4 mmol) and MeOH
(2 mL) were used, reaction time 15 h, yield 110 mg of dark green
(MeOH) lmax¼578 nm (log
1264, 1182, 1157, 1058, 1018, 949, 794 cmꢁ1. Anal. Calcd for
25H24BrN3S: C 62.76, H 5.06, N 8.78; found: C 62.44, H 4.91, N 8.58%.
3¼6.83); IR (ATR)
n¼2910, 1577, 1426,
solid (54%). Mp 264 ꢀC (decomp.); 1H NMR (DMSO-d6)
1H, J¼7.7 Hz, H7BT), 7.91 (d, 1H, J¼7.9 Hz, H4BT), 7.88 (d, 1H,
d
¼8.21 (d,
C

M. Zajac et al. / Tetrahedron 64 (2008) 10605–10618
10617
J¼14.2 Hz, C]CHb), 7.71–7.66 (m, 2H, H3PYR, H5BT), 7.61–7.54 (m,
Supplementary data
3H, H2Ph, H6Ph, H6BT), 7.38 (d, 1H, J¼16.0 Hz, C]CHd), 7.32 (d, 1H,
J¼14.3 Hz, C]CHa), 7.12 (d, 1H, J¼15.9 Hz, C]CHg), 7.05 (d,
1H, J¼4.6 Hz, H4PYR), 6.74 (d, 2H, J¼8.9 Hz, H3Ph, H5Ph), 6.11–5.97 (m,
1H, C]CH), 5.35 (d, 2H, J¼4.8 Hz, CH2), 5.32 (d, 1H, J¼11.5 Hz,
C]CH2), 5.22 (d, 1H, J¼17.1 Hz, C]CH2), 3.90 (s, 3H, CH3–NPYR),
Computational results of static molecular quadratic hyper-
polarizabilities b0 and electronic transition characteristics for all
conformers at B3LYP and HF level of theory. Supplementary data
associated with this article can be found in the online version, at
doi:10.1016/j.tet.2008.08.064.
2.98 (s, 6H, NMe2) ppm; 13C NMR (DMSO-d6)
d¼168.4, 150.8, 146.0,
141.0, 135.6, 134.8, 132.7, 130.7, 128.8, 128.6, 126.6, 126.2, 124.1,
123.6, 121.6, 118.5, 114.9, 112.2, 112.0, 110.3, 102.4, 48.6, 30.6 ppm
(the CH3–N signal is overlapped with the DMSO signal); UV–vis
References and notes
(MeOH) lmax¼624 nm (log
1527, 1407, 1376, 1240, 1107, 1048, 946, 803 cmꢁ1. Anal. Calcd for
27H28BrN3S: C 64.03, H 5.57, N 8.30; found: C 63.86, H 5.76, N 7.98%.
3
¼6.98); IR (ATR)
n
¼2988, 2900, 1566,
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4.5. Computational details
All molecular geometries were fully optimized at the BP86 level
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)
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*
Moreover, b0 values were estimated from the two-state model.44
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2
3
Dm12
ð
m12
Þ
b0
z
(1)
2
ðEmax
Þ
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´
´
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´
´
´
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4.6. Biological activity
The toxicity against an autotrophic form of unicellular flagellate
E. gracilis was monitored in a liquid Cramer–Myers medium con-
taining appropriate concentrations (2.0–300 mg/mL) of the test
12. Coe, B. J.; Harris, J. A.; Hall, J. J.; Brunschwig, B. S.; Hung, S.-T.; Libaers,
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aeruginosa CCM 8221) as well as against yeast (Candida albicans
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standard dilution method in Sabouraud medium.48
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