Facile, Regioselective Synthesis of Highly Solvatochromic Thiophene-Spaced N-Alkylpyridinium Dicyanomethanides for Second-Harmonic Generation

Article abstract of DOI:10.1021/jo970059x

The facile and clean synthesis of a novel class of highly solvatochromic chromophores 1 is reported. Compounds 1 are push-pull systems containing a negatively charged dicyanomethanide as a donor group and a positively charged N-alkylpyridinium as an acceptor group. The terminal polar functions are spaced by a thiophene-based moiety containing one or two heterocyclic rings and none, one, or two ethylene bridges. Chromophores 1 have been obtained through a general synthetic scheme involving, as the last step, the 100% regioselective alkylation of the precursor bidentate anions 2, where two competing nucleophilic sites, one neutral at the pyridic nitrogen and one anionic at the carbanionic carbon of the dicyanomethanide group, are present. The unprecedented highly regioselective attack of the alkylating agent onto the neutral pyridic nitrogen rather than the highly charged carbanionic carbon has been also confirmed in the case of the intermolecular competition. Multinuclear (¹³C and ¹⁵N) NMR spectroscopy has been used to investigate the structure and the extent of intramolecular charge transfer in 1, which are shown to exist in the ground state as highly charge-separated zwitterionic systems. Experimental results are discussed and compared with semiempirical (PM3) computations. The solvatochromic response of compounds 1, among the highest ever reported in the literature for similar systems, candidates this class of compounds as very attractive active components of nonlinear optical materials.

Full text of DOI:10.1021/jo970059x

J . Org. Chem. 1997, 62, 5755-5765
5755
F a cile, Regioselective Syn th esis of High ly Solva toch r om ic
Th iop h en e-Sp a ced N-Alk ylp yr id in iu m Dicya n om eth a n id es for
Secon d -Ha r m on ic Gen er a tion
Alessandro Abbotto, Silvia Bradamante, Antonio Facchetti, and Giorgio A. Pagani*
Dipartimento di Chimica Organica e Industriale dell’Universita` di Milano, and Centro CNR Speciali
Sistemi Organici, Via Golgi 19, I-20133 Milano, Italy
Received J anuary 10, 1997 (Revised Manuscript Received May 28, 1997X)
The facile and clean synthesis of a novel class of highly solvatochromic chromophores 1 is reported.
Compounds 1 are push-pull systems containing a negatively charged dicyanomethanide as a donor
group and a positively charged N-alkylpyridinium as an acceptor group. The terminal polar
functions are spaced by a thiophene-based moiety containing one or two heterocyclic rings and
none, one, or two ethylene bridges. Chromophores 1 have been obtained through a general synthetic
scheme involving, as the last step, the 100% regioselective alkylation of the precursor bidentate
anions 2, where two competing nucleophilic sites, one neutral at the pyridic nitrogen and one anionic
at the carbanionic carbon of the dicyanomethanide group, are present. The unprecedented highly
regioselective attack of the alkylating agent onto the neutral pyridic nitrogen rather than the highly
charged carbanionic carbon has been also confirmed in the case of the intermolecular competition.
Multinuclear (13C and 15N) NMR spectroscopy has been used to investigate the structure and the
extent of intramolecular charge transfer in 1, which are shown to exist in the ground state as
highly charge-separated zwitterionic systems. Experimental results are discussed and compared
with semiempirical (PM3) computations. The solvatochromic response of compounds 1, among the
highest ever reported in the literature for similar systems, candidates this class of compounds as
very attractive active components of nonlinear optical materials.
Much of the impetus for the study of systems that use
light as a carrier of information comes from the search
for materials that offer the possibility of extremely high-
speed data processing, transmission, and storage.1 Many
of these photonic systems require high-performance
nonlinear optical (NLO) materials,2,3 particularly those
that have second and third NLO effects.4 In the area of
electro-optical applications, early attempts included the
improvement of electronic biasing strengths by varying
classical donor and acceptor groups in push-pull sys-
tems,5 changing the substitution patterns, and varying
the extension of the conjugation between donor and
acceptor moieties.6,7 One of the strategies8 aimed at
increasing the first molecular hyperpolarizability â and
providing stability involves the insertion of five-mem-
bered heteroaromatics in the conjugated backbone. J en
et al. have shown that high â values can be achieved by
replacing benzenoid rings with easily delocalizable
thiophene moieties.9 Furthermore, thiophene-derived
chromophores have been recently developed with en-
hanced thermal stability.10 Within these compounds,
particularly large molecular hyperpolarizabilities were
found when dicyanovinyl and tricyanovinyl acceptors
were present.
Ab initio and semiempirical calculations have predicted
extremely large â values for heterocyclic betaines.11 This
class of NLO phores have recently attracted attention due
to their zwitterionic nature, which leads to high ground-
state dipole moments and large negative solvato-
chromism.12,13 In this connection, we have shown14 that
the 4-pyridine moiety is among the highest ranked
electron-acceptor groups, showing a charge demand15
c
(9) (a) Rao, V. P.; J en, A. K.-Y.; Wong, K. Y.; Drost, K. J . Tetrahedron
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K. Y.; J en, A. K.-Y.; Rao, V. P.; Drost, K. J . J . Chem. Phys. 1994, 100,
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Mater. 1994, 6, 494-496. (b) J en, A. K-Y.; Rao, V. P.; Drost, K. J .;
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(15) We have previously defined the charge demand cX of a sub-
stituent group X as the fraction of π-charge withdrawn from an
adjacent charged trigonal carbon atom and have subsequently used
charge demands as a measure of the capacity of group X to delocalize
positive or negative charge: (a) Bradamante, S.; Pagani, G. A. J . Chem.
Soc., Perkin Trans. 2 1986, 1035-1045. (b) Bradamante, S.; Pagani,
G. A. Pure Appl. Chem. 1989, 61, 709-716. (c) Barchiesi, E.; Brada-
mante, S.; Ferraccioli, R.; Pagani, G. A. J . Chem. Soc., Perkin Trans.
2 1990, 375-383.
X Abstract published in Advance ACS Abstracts, J uly 15, 1997.
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Optics: Chemical Perspectives; ACS Symposium Series, Vol. 455;
American Chemical Society: Washington, DC, 1991.
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Organic Molecules and Crystals; Academic Press: New York, 1987.
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Rev. 1994, 94, 243. (e) Dalton, L. R.; Harper, A. W.; Ghosn, R.; Steier,
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Y.; Shea, K. J . Chem. Mater. 1995, 7, 1060-1081. (f) Drost, K. J .; J en,
A. K.-Y.; Rao, V. P. CHEMTECH 1995, 25, 16-25
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S0022-3263(97)00059-5 CCC: $14.00 © 1997 American Chemical Society

5756 J . Org. Chem., Vol. 62, No. 17, 1997
Abbotto et al.
Sch em e 1a
a
Key: (i) NaCH(CN)2, DME, Pd(PPh3)4, overnight, rt; (ii) CF3SO3Me, acetone, overnight, rt.
that is comparable to that of a methoxycarbonyl group.
If the pyridic acceptor is alkylated at the nitrogen atom,
the strength of the group can become very high and
efficiently promote charge transfer from the donor moi-
ety.
also report on the solvatochromic response of compounds
1a -e, which is found to be among the highest reported
in the literature for analogous systems. Recently, our
group has prepared Langmuir-Blodgett films starting
with N-cetyl derivatives 1a ′,20 1b′, and 1c′.21
Because of the strict connection between solvato-
chromism and first hyperpolarizability,16 the aim of the
present work was to combine the various optimization
strategies and synthesize highly solvatochromic hybrid
molecules consisting of an N-alkylpyridinium ring (the
acceptor) bonded to a negatively charged dicyano-
methanide functionality (the donor) through a π-conju-
gated spacer group containing the thiophene ring. Com-
pounds 1 responded to these criteria. We considered as
a spacer moiety from one to three thiophene rings,
containing none or one or two ethylene bridges. Our
synthetic interest in push-pull systems17 based on
carbanions18,19 led us to consider carbanions 2 as the
closest precursor to the conjugated zwitterionic push-
pull compounds 1. Since carbanions 2 are ambident
nucleophiles, one site being the pyridyl nitrogen and the
second the dicyanomethyl carbanion fragment, we were
faced with the problem of developing a strategy that could
suitably control the regiochemistry of the electrophilic
attack of the alkylating agent.
Resu lts
Syn th esis of Zw itter ion ic Dyes 1. The synthesis
of compounds 1a -e is reported in Schemes 1 and 2. We
were not able to isolate the terthiophene-bridged dye 1f
for the reasons given below. Sodium salts 2 were
obtained from bromothiophenes 3 by reaction with ma-
lononitrile sodium salt in dimethoxyethane, using tet-
rakis(triphenylphosphine)palladium (0) as catalyst22
(Scheme 1). Sodium salts 2 can be easily isolated in a
pure form from the reaction mixture and are stable in
air. Carbanion 2a is stable for months in air, but
stability decreases on going from 2a to 2e. Compounds
2d and 2e start to decompose after a few days; they were
used for the synthesis of 1 preferably as soon as they were
obtained. These salts exhibit a particularly interesting
fluorescence in solution; for example, compound 2a has
a strong fluorescence band at λ ) 449 nm when irradiated
in acetone at λ ) 445 nm. All the bromo derivatives 3
are new compounds. They were obtained according to
(16) (a) Buckely, A.; Choe, E.; DeMartino, R.; Leslie, T.; Nelson, G.;
Starnatoff, J .; Stuetz, D.; Yoon, H. Polym. Mater. Sci. Eng. 1986, 54,
502. (b) Paley, M. S.; Harris, J . M.; Looser, H.; Baumert, J . C.;
Bjorklund, G. C.; J undt, D.; Twieg, R. J . J . Org. Chem. 1989, 54, 3774-
3778.
(17) (a) Abbotto, A.; Bradamante, S.; Capri, N.; Rzepa, H.; Williams,
D. J .; White, A. J . Org. Chem. 1996, 61, 1770-1778. (b) Bradamante,
S.; Facchetti, A.; Pagani, G. A. J . Phys. Org. Chem. 1997, in press.
(18) Abbotto, A.; Bradamante, S.; Pagani, G. A. J . Org. Chem. 1993,
58, 449-455.
(19) Abbotto, A.; Bradamante, S.; Pagani, G. A. J . Org. Chem. 1996,
61, 1761-1769.
(20) Ricceri, R.; Abbotto, A.; Facchetti, A.; Gabrielli, G.; Pagani, G.
A. Langmuir 1997, 13, 3434-3437.
(21) Ricceri, R.; Abbotto, A.; Facchetti, A.; Gabrielli, G.; Pagani, G.
A. Langmuir 1997, 13, 4182-4184.
(22) Yui, K.; Aso, Y.; Otsubo, T.; Ogura, F. Bull. Chem. Soc. J pn.
1989, 62, 1539-1546.
In this paper, we show the highly efficient and clean
access to the zwitterionic systems 1a -e and describe the
regioselective strategy that we used to achieve it. We

Synthesis of N-Alkylpyridinium Dicyanomethanides
J . Org. Chem., Vol. 62, No. 17, 1997 5757
Sch em e 2
Sch em e 3
Scheme 2 either by high-yield bromination of the thie-
nylpyridines 4a and 4b or via Horner-Wittig condensa-
tion between diethyl [(5-bromothien-2-yl)methyl]phos-
phonate and the proper aldehyde (4-pyridinecarbaldehydes
5d and 5e for the synthesis of 3c, 3d , and 3e, respec-
tively). No effective methods were known for the syn-
thesis of 4-(2-thienyl)pyridine (4a ), with the exception of
a coupling between 2-iodothiophene and 4-iodopyridine
in the presence of palladium amalgam, which occurred
with modest yields.23 We obtained pure compound 4a
in much more satisfactory yields (84%) via a palladium
complex-catalyzed cross-coupling reaction24 of the Grig-
nard reagent of 2-bromothiophene with 4-bromopyridine.
The same method was used for the synthesis of the
unknown 4-pyridylbisthiophene derivative 4b, as well as
the new 4-pyridylterthiophene derivatives 7 and 10
(Scheme 3). Deprotonation of 4a and subsequent quench-
ing with DMF led easily to 4-(5-formylthien-2-yl)pyridine
(5d ) in good yields. Also, the preparation of this com-
pound was previously reported25 from the coupling be-
tween 4-iodopyridine and 2-iodo-5-methylthiophene in
the presence of PdHg, followed by oxidation of the methyl
group with SeO2; again, yields were very modest. The
unknown aldehyde 5e was prepared similarly from 1-(4-
pyridyl)-2-(2-thienyl)ethylene (6), which was obtained
from the Horner-Wittig condensation between diethyl
[(2-thienyl)methyl]phosphonate and 4-pyridinecarbalde-
hyde with almost quantitative yields.26
not need particular precautions during storage. Solu-
tions of 1 are similarly stable but need to be stored in
the dark since stability is somewhat decreased in the
presence of light. Details on thermal and photochemical
stability, as well as results on decomposition of the dyes,
will be presented elsewhere.27
We were not able to isolate the terthiophene-bridged
chromophore 1f. The precursor carbanion 2f could not
be prepared from the bromo derivative 8 due to the too
scarce solubility of the reagent under the conditions
required for the coupling with the sodium salt of mal-
ononitrile (Scheme 3). We succeeded in improving the
solubility by introducing a C8-aliphatic chain on the
terminal thiophene ring. From the bromo derivative 11,
the sodium salt 12 was successfully obtained and iso-
lated. Unfortunately, the desired chromophore 13 was
extremely unstable under the reaction conditions, and
only a mixture of decomposition products was recovered.
We planned the regioselective alkylation of the sodium
salts 2 on considering the hard and soft properties of the
two nucleophilic sites present in the reagent. We envis-
aged the dicyanomethyl carbanion fragment as a soft
nucleophile, while we expected the pyridic one to be a
harder one.28 We therefore anticipated that hard alky-
lating agents such as alkyl triflates would favor the
selective formation of the N-alkylated derivative. Indeed,
carbanions 2a -e upon treatment with methyl triflates
All of the dyes 1 investigated in this study are
chemically stable as a solid in the air for months and do
(26) During the course of our work, a preparation of 6 was reported
from 2-thiophenecarbaldehyde and 4-picoline in acetic anhydride and
acetic acid with 66% yield: Pan, H.; Gao, X.; Zhang, Y.; Prasad, P. N.;
Reinhardt, B.; Kannan, R. Chem. Mater. 1995, 7, 816-821.
(27) Abbotto, A.; Bradamante, S.; Facchetti. A.; Pagani, G. A. Results
to be published.
(28) Pearson, R. G. In Advances in Linear Free Energy Relationship;
Chapman, N. B., Shorter, J ., Eds.; Plenum Press: London, 1972; p
281.
(23) Nakajima, R.; Iida, H.; Hara, T. Bull. Chem. Soc. J pn. 1990,
63, 636-637.
(24) Kumada, M. Pure Appl. Chem. 1980, 52, 669-679.
(25) Nakajima, R.; J amamoto, A. Hara, T. Bull. Chem. Soc. J pn.
1990, 63, 1968-1972.

5758 J . Org. Chem., Vol. 62, No. 17, 1997
Abbotto et al.
Ta ble 1. Solva toch r om ic Da ta [λm a x (n m ) of th e
Sch em e 4
Ch a r ge-Tr a n sfer Ba n d ] for th e Ch r om op h or es 1a -1e in
Selected Solven ts
MeOH
acetone
a
MeOH
∆λ
THF
a
compd MeOH CH3CN acetone THF CHCl3 ∆λ
1a
1b
1c
1d
1e
537
610
609
622
634
546
627
623
643
649
559
665
639
692
705
586
752
686
c
600
c
702
c
-22
-55
-30
-70
-71
-49 (-63)b
-142
-77 (-93)b
afforded exclusively the push-pull systems 1a -e, in the
satisfactory yields shown in Scheme 1. Analogously,
reaction with cetyl triflate led to the clean obtainment
of cetyl derivatives 1a ′-c′, which were used for the
preparation of Langmuir-Blodgett films.20,21 In contrast,
the reaction of dicyanomethyl carbanion 2a with the soft
methyl iodide afforded a complex, untractable mixture
of alkylated products (Scheme 4), where, along with the
desired chromophore 1a , solvatochromic inactive prod-
ucts deriving from alkylation of the carbanionic carbon
atom or from polyalkylation are likely to be present.
Although the favored attack to the pyridic nitrogen was
predicted by the use of the hard alkyl triflate, the clean
and exclusive obtainment of 1 was nevertheless surpris-
ing. We wanted to investigate this reaction in more
detail. In particular, we were interested in knowing if
the exclusive attack to the pyridic nitrogen was due to
the intrinsic nature of this electrophilic site or rather
promoted by the intramolecular charge transfer from the
negatively charged dicyanomethyl carbanionic center to
the heterocyclic ring. Consequently, we investigated the
intermolecular (vs. intramolecular) competitive alkyla-
tion between the two nucleophilic centers present in 2
by planning the model reactions presented in the next
paragraph.
c
c
a
∆λ ) λmax (polar solvent) - λmax (nonpolar solvent): positive
b
values ∆λ mean positive solvatochromism. ∆λ ) λmax (MeOH)
- λmax (CHCl3). c Compound not soluble.
Solva toch r om ic Da ta : Zw itter ion ic vs. Qu in oid ic
Str u ctu r e of 1. The description of the bonding in the
highly delocalized dipolar N-alkylpyridinium dicya-
nomethanides 1 could involve the quinoidic structures
1Q, where intermolecular charge transfer (CT) took place
from the negatively charged donor to the positively
charged heterocyclic acceptor. Both the ground state and
the excited state structures of molecules 1 can be de-
scribed as linear combination, with different coefficients,
of the two limit resonance formula 1 and 1Q.
In ter m olecu la r Regioselective Alk yla tion . We
conceived the two model molecules 2-thienylpyridine (4a )
and the sodium salt of phenylmalononitrile (14) as the
intermolecular equivalent of the two competing nucleo-
philic sites of 2a . The sodium salt 14 was obtained by
treatment of phenylmalononitrile29 with MeONa in MeOH
and isolated as a solid before running the subsequent
competitive alkylation. An equivalent mixture of the two
compounds 4a and 14 was submitted to alkylation either
with methyl triflate or methyl iodide in acetone. The
results are given in Scheme 5. Both reactions occurred
regioselectively with opposite results. The extent of
regioselectivity was determined by 1H-NMR. The action
of methyl triflate led to the preferential formation (ca.
80%) of the N-alkylated derivative 15a , whereas selective
obtainment (70%) of the C-alkylated product 16 was
observed in the case of the reaction with methyl iodide.
Although the degree of regioselectivity is lower than in
the case of the intramolecular competitive attack of the
two nucleophilic sites of anion 2a , the direction of the
regioselectivity is the same both for intramolecular and
intermolecular competition.
All of the compounds 1a -e present a strong CT band
in the visible region of the spectrum. Table 1 collects
absorption data relative to the CT band in selected
solvents. As an example, Figure 1 shows the absorption
spectra of compound 1c in four solvents of different
polarity, and it can be seen that the solvatochromic shift
from MeOH (ET ) 55.5) to THF (ET ) 37.4) is about 80
nm toward longer wavelengths. From the spectra re-
corded in solvents of different polarity, it was determined
that compounds 1 show a strong negative solvato-
chromism with respect to their CT absorption band, that
is, the position of the absorption maximum shifts to
shorter wavelengths with increasing the solvent polarity.
Within the conventional interpretation of solvatochromic
interactions,32 the negative solvatochromism indicates
that the value of the dipole moment in the excited state
is smaller than in the ground state. Although other
factors can affect the sign of solvatochromism (aggrega-
tion or different solvent polarizabilities),33 in the hypoth-
esis that the various solvents here considered do not
dramatically affect the electronic nature of the ground
and of the excited state, respectively, the result of a
negative solvatochromism indicates that the ground state
of 1 is better represented by the zwitterionic limit
formula 1.
With the exception of a very old report with no
spectroscopic data,30 2-cyano-2-phenylpropiononitrile (16)
was not previously described in the literature. The
N-methyl-4-(2-thienyl)pyridinium cation is known as
iodide31 but not as triflate. We prepared the pure
products 15a and 16 by the action of methyl triflate and
methyl iodide on 4a and phenylmalononitrile, respec-
tively.
1
The analysis of H, 13C, and 15N NMR spectra of the
(29) Suzuki, H.; Kobayashi, T.; Osuka, A. Chem. Lett. 1983, 589-
590.
chromophore 1a , and their comparison with spectra of
(30) Hessler, J . C. Am. Chem. J . 1908, 39, 63 (cf. Beilstein H, 9, 872
or Chem. Abstr. 1908, 2, 1003).
(31) Albers, W. M.; Canters, G. W.; Reedijk, J . Tetrahedron 1995,
51, 3895-3904.
(32) Reichardt, C. Solvent Effects in Organic Chemistry; Verlag
Chemie: New York, 1979; Chapter 6.
(33) Chen, C.-T.; Marder, S. R. Adv. Mater. 1995, 7, 1030-1033.

Synthesis of N-Alkylpyridinium Dicyanomethanides
J . Org. Chem., Vol. 62, No. 17, 1997 5759
Sch em e 5a
a
Key: (A) CF3SO3Me, acetone, rt; (B) MeI, acetone, rt.
makes compounds 1 very attractive and promising, as
confirmed by the large solvatochromic response.
The use of methyl triflate on the ambident anions 2
led to the N-alkylated zwitterionic compounds 1 in a
completely regioselective manner. The reported majority
of the selective alkylations concern 1,3-ambident nucleo-
philes only, involving systems centered on enolate, indolyl
anions, and the like.37 Very often, selectivity is obtained,
by varying the leaving group of the alkylating agent, the
counterion of the negatively charged ambident anion, the
solvent, and the temperature as well as adding chelating
molecules or inorganic salts38 (all factors that, more or
less directly, affect the nature and the concentration of
the monomeric, aggregated and mixed inorganic-organic
aggregated species present in solution).39 Without going
into the details of each of these factors, our aim was
simply that of having a supporting rationale for the
expected, but nonetheless surprising, behavior of 2a
toward electrophiles. For these reasons, we carried out
an intermolecular competition reaction exactly under the
same conditions (counterion, solvent, temperature, con-
centration) of the reaction of 2a with methyl triflate and
methyl iodide. Our results are the first examples in
which the competing nucleophiles are a carbanionic and
a neutral center, respectively, with an unprecedented
selectivity for the neutral one: they are a successful
experimental application, never treated before, of the
HSAB (hard and soft acids and bases) theory40 to
competing nucleophilic centers. The intermolecular con-
firmation of the direction of the N vs C alkylation with
F igu r e 1. UV-vis spectra of 1c in different solvents: THF,
-‚‚-; acetone, ‚‚‚; acetonitrile, s; methanol, - - -.
the charged precursor 2a , 4-(2-thienyl)pyridine (4a ), and
N-methyl-4-(2-thienyl)pyridinium triflate (15a ), provides
further information about the ground state structure and,
qualitatively, about the extent of the charge transfer from
the donor to the heterocyclic acceptor. All of the 13C and
15N chemical shift data are shown in Figure 2.
(35) See also, more recently: (a) Blenkle, M.; Boldt, P.; Bra¨uchle,
C.; Grahn, W.; Ledoux, I.; Nerenz, H.; Stadler, S.; Wichern, J .; Zyss,
J . J . Chem. Soc., Perkin Trans. 2 1996, 1377-1384. (b) Alain, V.; Fort,
A.; Barzoukas, M.; Chen, C.-T.; Blanchard-Desce, M.; Marder, S. R.;
Perry, J . W. Inorg. Chim. Acta 1996, 242, 43-49. (c) Ashwell, G. J .;
Walker, T. W.; Gentle, I. R.; Foran, G. J .; Bahra, G. S.; Brown, C. R.
J . Mater. Chem. 1996, 6, 969-974. (d) Ashwell, G. J .; J ackson, P. D.;
J efferies, G.; Gentle, I. R.; Kennard, C. H. L. J . Mater. Chem. 1996, 6,
137-141.
(36) (a) Ashwell, G. J .; Dawnay, E. J . C.; Kuczynski, A. P.; Sz-
ablewski, M.; Sandy, I. M.; Bryce, M. R.; Grainger, A. M.; Hasan, M.
J . Chem. Soc., Faraday Trans. 1990, 86, 1117-1121. (b) Ashwell, G.
J . Thin Solid Films 1990, 187, 155-165. (c) Ashwell, G. J .; Malhotra,
M.; Bryce, M. R.; Grainger, A. M. Synth. Met. 1991, 41-43, 3173-
3176. (d) Ashwell, G. J .; Hargreaves, R. C.; Baldwin, C. E.; Bahra, G.
S.; Brown, C. R. Nature 1992, 357, 393-395.
Discu ssion
This study reports the easy, clean, and high-yield
obtainment of a novel series of highly solvatochromic
systems for second-harmonic generation. The synthesis
scheme appears to be of general applicability and allows
access to a series of a potentially large class of chro-
mophores, with spacers of different structure and length.
Whereas the N-alkylpyridinium acceptor moiety was
already used as an acceptor in a number of chro-
mophores, including cyanine dyes, which are among the
most interesting systems for NLO applications,34,35 the
dicyanomethanide carbanion appeared as a donor only
in a limited series of benzenoid derivatives investigated
by Ashwell for the preparation of Langmuir-Blodgett
films.36 The inclusion of a thiophene-based spacer9
(37) Reutov, O. A.; Beletskaya, I. P.; Kurts, A. L. Ambident Anions;
Consultants Bureau: New York, 1983.
(38) See, for instance, the investigation on the C/O alkylation ratio
of lithium enolates: (a) J ackman, L. M.; Lange, B. C. J . Am. Chem.
Soc. 1981, 103, 4494. (b) J ackman, L. M.; Dunne, T. S. J . Am. Chem.
Soc. 1985, 107, 2805.
(39) (a) J ackman, L. M.; Rakiewicz, E. F. J . Am. Chem. Soc. 1991,
113, 1202. (b) Abbotto, A.; Streitwieser, A. J . Am. Chem. Soc. 1995,
117, 6358-6359. (c) Abu-Hasanayn, F.; Stratakis, M.; Streitwieser, A.
J . Org. Chem. 1995, 60, 4688-4689. (d) Abu-Hasanayn, F.; Streit-
wieser, A. J . Am. Chem. Soc. 1996, 118, 8136-8137.
(34) Bosshard, C.; Sutter, K.; Preˆtre, P.; Hulliger, J .; Flo¨rsheimer,
M.; Kaatz, P.; Gu¨nter, P. In Organic Nonlinear Optical Materials In
Advances in Nonlinear Optics; Garito, A. F., Kajzar, F., Eds.; Gordon
and Breach Publishers: Basel, 1995; Vol. 1.
(40) Pearson, R. G. Hard and Soft Acids and Bases; Dowden,
Hutchinson and Ross: Stroudsville, PA, 1973.

5760 J . Org. Chem., Vol. 62, No. 17, 1997
Abbotto et al.
F igu r e 2. 13C (roman type) and 15N (italic type) NMR data in DMSO at 27 °C for compounds 4a , 2a , 1a , and 15a (assignments
marked with an asterisk are tentative).
Sch em e 6
involved atom must have the same substitution pattern
in both compounds associated with the shift variation.
The validity of these relationships was assessed by its
successful application to a high number of aliphatic,
aromatic, and heteroaromatic derivatives.14,15,18,19,41
methyl triflate excludes the fact that the origin of the
exclusive electrophilic attack to the pyridic nitrogen of
2a is a possible charge transfer from the dicyanomethanide
moiety to the heterocyclic ring. According to the NMR
analysis that will be discussed below, the charge transfer
in carbanion 2a is very limited, and the negative charge
residing on the pyridic nitrogen is comparable to that of
4-(2-thienyl)pyridine (4a ). Nevertheless, the results of
the intermolecular competition show very clearly that
toward methyl triflate the neutral pyridine derivative is
much more reactive than the competitive carbanionic
nucleophile. To our knowledge, this is the first example
where a neutral species is found to be much more reactive
than the classical highly nucleophilic cyano-disubstituted
carbanion in a reaction with an energetic electrophilic
agent. Also, for the first time, a negatively charged
carbanionic carbon is not perturbed by the reaction with
a strong methylating agent and is found unaltered in the
product. This result is even more impressive in view of
the fact the negative charge is almost completely localized
on the carbanionic carbon of the dicyanomethanide
moiety of 2a and not on the heterocyclic rings (see below)
or the cyano groups.18 Finally, the same complete
regioselectivity was found in the reaction with the hard
hydronium ion: treatment of 2a with hydrochloric acid
led exclusively to the product 17 protonated at the pyridic
nitrogen (Scheme 6).
∆δ13C ) -160∆qπC
(1)
(2)
∆δ13N ) -366.34∆qπN
Comparison between 4a and 2a shows that the intro-
duction of the dicyanomethanide carbanion group does
not significantly affect the electronic distribution in 2a .
The 15N shift of 4a is typical of a substituted pyridine.42
The pyridic nitrogen experiences a small increase (∆q )
0.028)43 of π-electron density, whereas the mean increase
for the carbon atoms of the two heterocyclic rings is
almost zero.44 We can therefore conclude that more than
90% of the negative charge is localized on the dicya-
nomethanide moiety. We have previously shown18 that
the charge demand15 of the cyano groups is very modest.
In the sodium salt of malononitrile, where the 13C shift
of the carbanionic carbon is -0.25 ppm (DMSO), almost
60% of the negative charge is localized on this atom. A
more proper comparison is, however, with the sodium salt
of phenylmalononitrile, where the substitution of the
carbanionic carbon is closer to that of 2a . In this anion,
the 13C shift of the central carbon atom is 27.11 ppm
(DMSO),18 which corresponds to a negative π-charge of
0.50 electrons (localized on this site). The chemical shift
of the corresponding site of 2a (28.27 ppm) and the above
The analysis of the 13C and 15N NMR of 1a and their
comparison with the synthetic precursors or models 2a ,
15a , and 4a gives very useful and detailed insights on
its structure and electronic distribution (see Figure 2).
We have previously proposed the π-electron density/shift
relationships (1)15a and (2)41 for 13C and 15N, respectively,
which allow the empirical calculation of the variation of
the electron density of a sp2 carbon or nitrogen atom,
respectively, upon variation of the chemical shift. The
(42) Witanowski, M.; Stefaniak, L.; Webb, G. A. In Annual Reports
on NMR Spectroscopy; Webb, G. A., Ed.; Academic Press: London,
1986; Vol. 18.
(43) A positive value of ∆q corresponds to an increase in π-electron
density.
(44) The difference between (Σδ13C)rings going from 4a to 2a is only
-7.4 ppm, corresponding to a total ∆q of 0.05 electrons. Although
differently substituted, it is justified to compare C-2′ in 4a and in 2a
since the shielding contribution of the group CH(CN)2 is almost zero
(as can be seen by comparing the 13C chemical shift of benzene with
that of Cipso in phenylmalononitrile).18 Finally, we assume that the
sulfur atom does not delocalize any negative charge. This was
confirmed in an earlier study of R-thiazolylmethyl carbanions.19
(41) See ref 18 and: (a) Abbotto, A.; Alanzo, V.; Bradamante, S.;
Pagani, G. A. J . Chem. Soc., Perkin Trans. 2 1991, 481-488. (b)
Abbotto, A.; Bradamante, S.; Pagani, G. A. J . Org. Chem. 1993, 58,
444-448. (c) Gatti, C.; Ponti, A.; Gamba, A.; Pagani, G. A. J . Am. Chem.
Soc. 1992, 114, 8634-8644.

Synthesis of N-Alkylpyridinium Dicyanomethanides
J . Org. Chem., Vol. 62, No. 17, 1997 5761
considerations led us to conclude that a considerable
quantity of negative π-charge is resident on the carban-
ionic carbon. In view of this result, the regioselectivity
of the electrophilic attack appears even more surprising.
Similar conclusions can be drawn by comparing the
chemical shifts of 1a and 15a . The pyridic nitrogen in
the former is modestly high-field shifted with respect to
15a . Its chemical shift, and therefore the corresponding
π-electron density, is that typical of a pyridinium salt.
On going from 15a to 1a there is an increase in the
electron density of the nitrogen atom by only 0.05
electrons, which corresponds exactly to the decrease (by
0.05 electrons) experienced by the carbanionic carbon
atom on going from 2a to 1a . In conclusion, apart from
this almost negligible charge transfer, the electronic
structure of the sample chromophore 1a resembles, on
the N-alkylpyridinium side, that of a simple pyridinium
salt, like 15, and on the dicianomethanide portion, that
of a localized carbanion salt, like 2a . That is, the ground-
state electronic structure of 1a is, at least in DMSO, that
of a highly charge-separated zwitterionic system.
semiempirical theoretical approach is not able to compute
adequately the chromophores 1. If, instead, PM3 calcu-
lations are assumed to be sufficiently reliable, we must
conclude that the chromophores 1 are intrinsically
(semiempirical calculations) better described by the
neutral quinoidic structure 1Q and that the charge-
separated zwitterionic formula is more relevant only in
solution (experimental data). The latter can be consid-
ered a realistic situation since it is likely that polar
solvents like DMSOswhere NMR analysis was per-
formed47sor the ones used in the solvatochromic study
(from MeOH to CHCl3) favor the charge-separated form
thanks to stabilizing intermolecular interactions. In any
case, the calculated â values are not reported due to the
inadequacy of computations to describe accurately the
situation in solution, where experimental EFISH or
hyper-Rayleigh scattering48 measures are generally per-
formed.
On the basis of the highly zwitterionic ground state
structure of 1 and the dipole moment values calculated
semiempirically for the neutral and charge-separated
forms, it is justified to expect a large difference between
the dipole moments of the ground and excited states of 1
in solution. According to the two-state model49 derived
from the perturbation theory, the dyes 1 should exhibit
large negative â values. These expectations are experi-
mentally corroborated by the very large solvatochromic
response of compounds 1a -e, which is among the largest
reported in the literature for similar type of systems. As
an example, the merocyanine dye 18, which shows the
There are some additional experimental facts that
support this conclusion. Firstly, the absence of hindered
rotation for the carbon atoms of the pyridine ring
suggests that the quinoidic limit structure 1Q is not
important in the description of the chromophores 1. In
fact, we have previously shown that in correspondence
of a charge delocalization on the 4-pyridine ring, the
consequent double-bond character of the exocyclic bond
has the effect to make the pyridine C-3 and C-5 shifts
extremely large âµ value of 7600 × 10-48 esu,50 has a
3
anisochronous.41b Secondly, the value of the J H-H cou-
MeOH
CHCl3
solvatochromic response of ∆λ
) -128 nm,51 which
pling constants of the central trans carbon-carbon double
bond in the chromophore 1c (15 Hz) is almost identical
to that of the anionic precursor 2c (15.9 Hz) and of the
simple ethylene derivative 6 (16.1 Hz), where neither the
donor nor the acceptor group are present. Finally, the
crystallographic analysis of a 2-pyridine benzenoid analog
of our systems 1 showed the zwitterionic nature of the
chromophore.45
is comparable to those recorded in this study.52
Con clu sion s
In this study, we have prepared a novel class of
compounds 1 for second-harmonic generation using a
high-yield clean procedure of general applicability. In
the 100% regioselective alkylation carried out to prepare
1 from the bidentate nucleophilic precursors 2, for the
first time a neutral site has been found to be much more
reactive than a highly negatively charged carbanionic
center with respect to hard electrophiles. The same
surprising result was obtained when competitive inter-
molecular nucleophilic attacks were investigated. The
structure of 1 in solution was determined by multinuclear
NMR analysis and other experimental data to be almost
exclusively described by the charge-separated zwitteri-
onic limit formula 1, with highly localized positive and
negative charges. Since in the gas phase the structure
of 1 is computed to be preferentially quinoidic, it was
concluded that the zwitterionic structure is stabilized by
solvent-dye intermolecular interactions. The solvato-
chromic response of 1 was found to be very large, with
respect to values reported in the literature for similar
compounds. This and other data suggest that large
molecular hyperpolarizabilities should be exhibited by
these chromophores.53
Semiempirical calculations have been carried out using
the program MOPAC 6.046 with the aim to calculate the
dipole moments of the ground and excited state and the
first molecular hyperpolarizabilities of compounds 1a -
e. Computations have been performed in the gas phase
using the keywords PM3, EF, PRECISE, and POLAR for
the ground state and PM3 and EXCITED for the excited
state. Geometries were fully optimized without any
symmetry constraint. All of the structures were quinoidic
in the ground state with a high charge transfer from the
carbanionic carbon to the pyridic nitrogen. Calculated
bond lengths are in accord with the description of the
chromophore as the limit formula 1Q. For compound 1a
the σ-charge and π-charge for the carbanionic carbon of
the dicyanomethanide moiety are calculated to be +0.19
and -0.22, respectively. Corresponding values for the
nitrogen atom are +0.45 and -0.63, respectively. Cal-
culated charges for the other compounds 1 are similar
to that of 1a and are not reported. The ground state
dipole moment ranges from 13.9 to 15.6 D. The excited
state dipole moment of 1a is calculated to be 33.6 D. It
is clear that, in terms of contribution of the zwitterionic
and quinoidic limit formulas in the ground state struc-
ture, computations give an opposite description with
respect to experimental evidence. It is possible that the
(47) Less polar solvents could not be considered due to solubility
limits.
(48) See ref 34, p. 117.
(49) Oudar, J . L.; Chemla, D. S. J . Chem. Phys. 1977, 66, 2664.
(50) Dulcic, A.; Flytzanis, C. Opt. Commun. 1978, 25, 402.
(51) Benson, H. G.; Murrell, J . N. J . Chem. Soc., Faraday Trans.2
1972, 68, 137-143.
(52) For instance, for compound 1b solvatochromism recorded
between MeOH and THF is -142 nm (it must be noted that the
corresponding data between MeOH and CHCl3 is expected to be larger,
as can be seen from Table 1).
(45) Metzger, R. M.; Heimer, N. E.; Ashwell, G. J . Mol. Cryst. Liq.
Cryst. 1984, 107, 133.
(46) Stewart, J . J . P. QCPE 455, 1990.

5762 J . Org. Chem., Vol. 62, No. 17, 1997
Abbotto et al.
was added dropwise to a suspension of 4-[5-(dicyanomethani-
do)thien-2-yl]pyridine sodium salt (2a ) (2.00 g, 8.09 mmol) in
dry acetone (100 mL). The color of the mixture immediately
changed from yellow to violet. After being stirred overnight
at room temperature, the precipitate was collected and washed
with water and then with EtOH to give the analytically pure
product (1.51 g, 6.32 mmol, 78%) as a violet solid: mp > 240
°C; 1H NMR (DMSO-d6) δ 8.26 (d, 2 H, J ) 7.0), 7.92 (d, 1 H,
J ) 4.4), 7.62 (d, 2 H, J ) 7.0), 6.41 (d, 1 H, J ) 4.4), 3.96 (s,
3 H). Anal. Calcd for C13H9N3S: C, 65.26; H, 3.79; N, 17.57.
Found: C, 65.10; H, 3.81; N, 17.23.
2-(4-N -C e t y lp y r i d i n i u m )-5-(d i c y a n o m e t h a n i d o )-
th iop h en e (1a ′). A solution of trifluoromethanesulfonic
anhydride (0.62 g, 2.20 mmol) in CH2Cl2 (5 mL) was added, in
a period of 15 min, to a solution of cetyl alcohol (0.50 g, 2.06
mmol) in the same solvent (8 mL). After being stirred at room
temperature for 20 min, the reaction mixture was poured onto
ice (20 mL), and then the organic layer was washed with water,
dried, and evaporated to leave the crude cetyl triflate (0.64 g,
1.71 mmol, 83.0%). Cetyl triflate (0.64 g, 1.71 mmol) in dry
acetone (10 mL) was added dropwise to a suspension of 4-[5-
(dicyanomethanido)thien-2-yl]pyridine sodium salt (2a ) (0.47
g, 1.71 mmol) in the same solvent (10 mL). The color of the
mixture immediately changed from yellow to violet. After the
mixture was stirred for 12 h at room temperature, the
precipitate was collected and washed with H2O and then with
EtOH to give the product (0.25 g, 0.56 mmol, 33%) as a violet
solid: mp 207-208 °C (EtOH); 1H NMR (DMSO-d6) δ 8.31 (d,
2 H, J ) 7.8), 7.92 (d, 1 H, J ) 4.2), 7.58 (d, 2 H, J ) 7.8), 6.41
(d, 1 H, J ) 4.2), 4.20 (t, 2 H, J ) 7.1), 1.85-1.70 (m , 2 H),
1.40-1.10 (m, 26 H), 0.85 (t, 3 H, J ) 7.1); UV-vis (DMF)
λmax ) 551 nm, ꢀ ) 75 700 ( 600 M-1 cm-1. Anal. Calcd for
C28H39N3S: C, 74.79; H, 8.75; N, 9.35. Found: C, 75.17; H,
8.77; N, 9.65.
4-[5-(2-Th ien yl)th ien -2-yl]p yr id in e (4b). 5-(2,2′-Bithie-
nyl)magnesium bromide was prepared by adding a solution
of 5-bromo-2,2′-bithiophene54 (1.72 g, 7.01 mmol) in anhydrous
diethyl ether (5 mL) to a suspension of magnesium (0.21 g,
8.73 mmol) in the same solvent (10 mL). The reaction mixture
was refluxed for 45 min under nitrogen. After cooling, the
Grignard solution was added dropwise to a stirred suspension
of 4-bromopyridine (0.95 g, 6.01 mmol) and PdCl2(dppf) (0.04
g, 0.05 mmol) in the same solvent (15 mL), maintaining the
temperature at -20 °C. After being stirred for 4 h at 0-5 °C
and overnight at room temperature, the reaction mixture was
poured into a saturated aqueous ammonium chloride solution
(30 mL), and the aqueous layer was extracted with methylene
chloride (4 × 30 mL). The combined organic layers were
washed with H2O and dried, and the solvent was evaporated
to leave a brown solid (1.20 g), which was submitted to flash
chromatography (diethyl ether-petroleum ether 1:1) on silica
gel. The title product was obtained as a yellow solid (0.88 g,
3.61 mmol, 60%): mp 147-148 °C. A pure analytical sample
was obtained by sublimation (110 °C/0.005 mmHg): mp 148
°C; 1H NMR (CDCl3) δ 8.57 (d, 2 H, J ) 6.1), 7.44 (d, 2 H, J )
6.1), 7.41 (d, 1 H, J ) 3.9), 7.26 (d, 1 H, J ) 5.1), 7.23 (d, 1 H,
J ) 3.7), 7.16 (d, 1 H, J ) 3.9), 7.03 (dd, 1 H, J ) 5.1, 3.7).
Anal. Calcd for C13H9NS2: C, 64.15; H, 3.74; N, 5.76. Found:
C, 64.24; H, 3.68; N, 5.58.
Exp er im en ta l Section
1H NMR spectra were recorded at 300 and 500 MHz.
Coupling constants are reported in Hz. Mass spectra were
determined at an ionizing voltage of 70 eV. Anhydrous
solvents were prepared by continuous distillation over sodium
sand, in the presence of benzophenone and under nitrogen or
argon, until the blue color of sodium ketyl was permanent.
Anhydrous N,N-dimethylformamide (DMF) was supplied by
Fluka. Acetone was dried over Na2SO4 for
a few days.
Diisopropylamine was refluxed over CaH2 for 4 h and distilled
under nitrogen prior to use. Extracts were dried over Na2SO4
(4 h). Melting points are uncorrected.
Ma ter ia ls. 4-Pyridinecarbaldehyde and 2-bromothiophene
are commercially available (Fluka). The unstable 4-bromopy-
ridine as a free base was obtained from the commercially
available hydrochloride (Fluka), by addition to its aqueous
solution of an equimolar amount of potassium carbonate at 0
°C. Extraction with diethyl ether, drying of the organic layers,
and evaporation of the solvent below 30 °C yielded almost pure
4-bromopyridine. Because of its instability, it was used
immediately for further reactions.
4-(2-Th ien yl)p yr id in e (4a ). 2-Thienylmagnesium bro-
mide was prepared by adding a solution of 2-bromothiophene
(9.27 g, 56.86 mmol) in anhydrous diethyl ether (70 mL) to a
suspension of magnesium (1.71 g, 70.34 mmol) in the same
solvent (20 mL). This Grignard solution was kept under dry
nitrogen atmosphere and added dropwise to a stirred suspen-
sion of 4-bromopyridine (8.01 g, 50.70 mmol) and PdCl2(dppf)
(0.319 g, 0.43 mmol) in the same solvent (30 mL), maintaining
the temperature between -30 and -20 °C. A white precipitate
formed immediately. After being stirred for 2 h at 0-5 °C,
the reaction mixture was poured into a saturated aqueous
ammonium chloride solution (120 mL), and the aqueous layer
was extracted with diethyl ether (3 × 60 mL). The combined
organic layers were dried, and the solvent was evaporated to
give the practically pure compound as a light yellow solid (6.86
g, 42.55 mmol, 84%): mp 87-88 °C (lit.23 mp 93-94 °C); H
NMR (CDCl3) δ 8.59 (d, 2 H, J ) 4.8), 7.51 (d, 1 H, J ) 3.8),
7.49 (d, 2 H, J ) 4.8), 7.41 (d, 1 H, J ) 5.0), 7.13 (dd, 1 H, J
) 5.0, 3.8).
1
4-(5-Br om oth ien -2-yl)p yr id in e (3a ). Bromine (13.54 g,
85.06 mmol) was added to a solution of 4-(2-thienyl)pyridine
(4a ) (6.86 g, 42.55 mmol) in methylene chloride (300 mL). After
being stirred for 15 min at room temperature, the reaction
mixture was poured onto 10% aqueous K2CO3 (300 mL), and
the aqueous layer was extracted with methylene chloride
(2 × 100 mL). The combined organic layers were dried, and
the solvent was evaporated to give a brown solid (9.51 g) that,
after sublimation, afforded the pure product (8.41 g, 35.02
mmol, 82%): mp 152-153 °C (EtOH); 1H NMR (CDCl3) δ 8.57
(d, 2 H, J ) 6.1), 7.36 (d, 2 H, J ) 6), 7.24 (d, 1 H, J ) 4.0),
7.08 (d, 1 H, J ) 4). Anal. Calcd for C9H6BrNS: C, 45.02; H,
2.52; N, 5.83. Found: C, 45.20; H, 2.66; N, 6.17.
4-[5-(Dicya n om et h a n id o)t h ien -2-yl]p yr id in e Sod iu m
Sa lt (2a ). Malononitrile (5.92 g, 89.94 mmol) was added
portionwise to an ice-cooled suspension of sodium hydride (7.19
g, 60% in oil, 179.75 mmol) in 1,2-dimethoxyethane (300 mL),
and the mixture was stirred at room temperature for 20 min
under nitrogen. 4-(5-Bromothien-2-yl)pyridine (3a ) (8.85 g,
36.85 mmol) and tetrakis(triphenylphosphine)palladium(0)
(4.33 g, 3.75 mmol) were added to the above solution, and the
mixture was heated under reflux for 2 h. The resulting
precipitate was collected by filtration, washed with benzene
(30 mL) to eliminate the catalyst, and then recrystallized from
H2O to give the product as a yellow solid (3.62 g, 13.20 mmol,
4-[[5-(5-Br om oth ien -2-yl)]th ien -2-yl]p yr id in e (3b).
A
solution of N-bromosuccinimide (0.40 g, 2.2 mmol) in anhy-
drous DMF (25 mL) was added dropwise to a solution of 4-[5-
(2-thienyl)thien-2-yl]pyridine (4b) (0.50 g, 2.0 mmol) in the
same solvent (25 mL) under nitrogen in the dark. After being
stirred for 2 h at room temperature, keeping the reaction flask
removed from light, the mixture was poured onto ice (50 mL)
and extracted with methylene chloride (4 × 40 mL). The
combined organic layers were washed with H2O, dried, and
evaporated to dryness to give the product as a light brown solid
(0.65 g, 2.0 mmol, 100%): mp 153 °C (EtOH); 1H NMR (CDCl3)
δ 8.57 (d, 2 H, J ) 5.9), 7.42 (d, 2 H, J ) 5.9), 7.39 (d, 1 H, J
) 3.9), 7.10 (d, 1 H, J ) 3.9), 6.99 (d, 1 H, J ) 3.9), 6.97 (d, 1
H, J ) 3.9). Anal. Calcd for C13H8BrNS2: C, 48.45; H, 2.51;
N, 4.35. Found: C, 48.11; H, 2.71; N, 4.52.
1
36%): mp > 240 °C; H NMR (DMSO-d6) δ 8.31 (d, 2 H, J )
6.3), 7.43 (d, 1 H, J ) 3.1), 7.27 (d, 2 H, J ) 6.3), 6.11 (d, 1 H,
J ) 3). Anal. Calcd for C12H6N3NaS: C, 58.30; H, 2.45; N,
17.01. Found: C, 57.87; H, 2.43; N, 16.59.
2-(4-N -Me t h ylp yr id in iu m )-5-(d ic y a n o m e t h a n id o)-
th iop h en e (1a ). Methyl triflate (1.32 g, 0.88 mL, 8.09 mmol)
(53) Preliminary EFISH measures for compounds 1a and 1c in
CHCl3 solutions indicate âµ values of ca. -7000 and -13000 × 10-48
esu at λ ) 1.9 µm, respectively. Full data of the measures currently in
progress will be reported elsewhere.
(54) Rossi, R.; Carpita, A.; Ciofalo, M.; Nouben, J . L. Gazz. Chim.
Ital. 1985, 115, 575.

Synthesis of N-Alkylpyridinium Dicyanomethanides
J . Org. Chem., Vol. 62, No. 17, 1997 5763
4-[[5-[5-(Dicya n om eth a n id o)th ien -2-yl]]th ien -2-yl]p y-
r id in e Sod iu m Sa lt (2b). Malononitrile (0.32 g, 4.77 mmol)
was added to an ice-cooled suspension of sodium hydride (0.38
g, 60% oily, 9.50 mmol) in anhydrous 1,2-dimethoxyethane (30
mL), and under nitrogen atmosphere, the mixture was stirred
at room temperature for 30 min. 4-[[5-(5-Bromothien-2-
yl)]thien-2-yl]pyridine (3b) (0.58 g, 1.80 mmol) and tetraki-
s(triphenylphosphine)palladium(0) (0.23 g, 0.20 mmol) were
added to the above solution, and the mixture was stirred
overnight at room temperature. The solvent was removed
under reduced pressure, and the resulting solid was taken up
with benzene (2 × 10 mL) to eliminate the catalyst and then
washed with H2O (5 mL) to give the product as a red solid
(0.52 g, 1.57 mmol, 87%): mp > 240 °C; this was used without
further purification in the next step; 1H NMR (DMSO-d6) δ
8.49 (d, 2 H, J ) 6.0), 7.67 (d, 1 H, J ) 3.9), 7.53 (d, 2 H, J )
6.0), 7.02 (d, 1 H, J ) 3.9), 6.98 (d, 1 H, J ) 3.9), 6.03 (d, 1 H,
J ) 3.9).
mL), and under nitrogen atmosphere, the mixture was stirred
at room temperature for 20 min. 1-(4-Pyridyl)-2-(5-bromothien-
2-yl)ethylene (3c) (1.00 g, 3.76 mmol) and tetrakis(triph-
enylphosphine)palladium(0) (0.43 g, 0.37 mmol) were added
to the above solution, and the mixture was stirred overnight
at room temperature. The solvent was removed under reduced
pressure, and the resulting solid (2.68 g) was taken up with
benzene (2 × 30 mL) and washed with H2O (40 mL) to give
the product as an orange solid (0.95 g, 3.48 mmol, 92%): mp
> 240 °C (H2O); 1H NMR (DMSO-d6) δ 8.36 (dd, 2 H, J ) 6.1,
1.4), 7.50 (d, 1 H, J ) 15.9), 7.34 (dd, 2 H, J ) 6.1, 1.4), 6.89
(d, 1 H, J ) 3.8), 6.24 (d, 1 H, J ) 16), 6.02 (d, 1 H, J ) 3.8).
Anal. Calcd for C14H8N3NaS‚H2O: C, 57.72; H, 3.46; N, 14.42.
Found: C, 57.65; H, 3.66; N, 14.32.
1-(4-N-Met h ylp yr id in iu m )-2-[5-(d icya n om et h a n id o)-
th ien -2-yl]eth ylen e (1c). A procedure similar to that used
for the synthesis of 2-(4-N-methylpyridinium)-5-(dicyano-
methanido)thiophene (1a ) was employed. From the sodium
salt 2c (0.20 g, 0.73 mmol) and methyl triflate (0.12 g, 0.73
mmol) was obtained the title product as a blue solid (0.18 g,
2-(4-N-Met h ylp yr id in iu m )-5-[5-(d icya n om et h a n id o)-
th ien -2-yl]th ien e (1b). A procedure similar to that used for
the synthesis of 3-(4-N-methylpyridinium)-5-(dicyanomethani-
do)thiophene (1a ) was employed. From the sodium salt 2b
(0.100 g, 0.33 mmol) and methyl triflate (0.053 g, 0.33 mmol)
was obtained the title product as a very dark solid (0.083 g,
1
0.68 mmol, 93%): mp > 240 °C; H NMR (DMSO-d6) δ 8.38
(d, 2 H, J ) 6.8), 7.96 (d, 1 H, J ) 15.2), 7.73 (d, 2 H, J ) 6.8),
7.18 (d, 1 H, J ) 4.2), 6.32 (d, 1 H, J ) 15), 6.25 (d, 1 H, J )
4), 4.00 (s, 3 H). Anal. Calcd for C15H11N3S: C, 67.90; H, 4.18;
N, 15.84. Found: C, 67.64; H, 4.32; N, 15.58.
1
0.26 mmol, 78%): mp > 240 °C; H NMR (DMSO-d6) δ 8.65
(d, 2 H, J ) 6.7), 8.10 (d, 1 H, J ) 4.1), 8.05 (d, 2 H, J ) 6.7),
7.27 (d, 1 H, J ) 3.9), 7.20 (d, 1 H, J ) 3.9), 6.15 (d, 1 H, J )
4.1), 4.15 (s, 3 H). Anal. Calcd for C17H11N3S2: C, 63.53; H,
3.45; N, 13.07. Found: C, 63.29; H, 3.29; N, 13.12.
1-(4-N-Cetylpyr idin iu m )-2-[5-(dicyan om eth an ido)th ien -
2-yl]eth ylen e (1c′). Cetyl triflate (0.85 g, 2.27 mmol) in dry
acetone (13 mL) was added dropwise to a suspension of 1-(4-
pyridyl)-2-[5-(dicyanomethanido)thien-2-yl]ethylene sodium salt
(2c) (0.62 g, 2.27 mmol) in the same solvent (13 mL). The
color of the mixture immediately changed from orange to blue.
After the mixture was stirred overnight at room temperature,
the precipitate was collected and washed with EtOH to give
the practically pure product (0.83 g, 1.74 mmol, 77%) as a blue
solid: mp 238-239 °C (EtOH); 1H NMR (DMSO-d6) δ 8.43 (d,
2 H, J ) 7.0), 7.96 (d, 1 H, J ) 15.1), 7.71 (d, 2 H, J ) 7), 7.20
(d, 1 H, J ) 4.2), 6.30 (d, 1 H, J ) 15), 6.27 (d, 1 H, J ) 4),
4.24 (t, 2 H, J ) 7.1), 1.85-1.75 (m, 2 H), 1.40-1.10 (m , 26
H), 0.85 (t, 3 H, J ) 7.1); UV-vis (DMF) λmax ) 629 nm, ꢀ )
79 500 ( 400 M-1cm-1. Anal. Calcd for C30H41N3S: C, 75.74;
H, 8.69; N, 8.83. Found: C, 75.47; H, 8.85; N, 8.69.
2-(4-N-Cetylpyr idin iu m )-5-[5-(dicyan om eth an ido)th ien -
2-yl]th iop h en e (1b′). Cetyl triflate (0.114 g, 0.30 mmol) in
dry acetone (3 mL) was added dropwise to a suspension of the
sodium salt 2b (0.100 g, 0.30 mmol) in the same solvent (4
mL). After the mixture was stirred for 4 h at room temper-
ature, the precipitate was collected to give the product (0.080
1
g, 0.15 mmol, 50%) as a dark solid: mp > 240 °C (DMF); H
NMR (DMSO-d6) δ 8.67 (d, 2 H, J ) 6.4), 8.07 (d, 1 H, J )
3.9), 8.01 (d, 2 H, J ) 6.4), 7.24 (d, 1 H, J ) 4.3), 7.17 (d, 1 H,
J ) 4.3), 6.16 (d, 1 H, J ) 3.9), 4.35 (t, 2 H, J ) 7.0), 1.92-
1.80 (m, 2 H), 1.35-1.15 (m, 26 H), 0.82 (t, 3 H, J ) 7.1). Anal.
Calcd for C32H41N3S2: C, 72.25; H, 7.78; N, 7.90. Found: C,
72.05; H, 7.83; N, 7.86.
4-(5-For m ylth ien -2-yl)pyr idin e (5d). A solution of lithium
diisopropylamide (LDA) in anhydrous diethyl ether [prepared
in situ from freshly distilled diisopropylamine (3.16 g, 31.0
mmol) and n-BuLi 1.6 M in hexane (19.4 mL, 31.0 mmol) in
anhydrous diethyl ether (20 mL) at room temperature under
nitrogen] was added dropwise to a solution of 4-(2-thienyl)py-
ridine (4a ) (2.50 g, 15.5 mmol) in the same solvent (50 mL) at
-10 °C under nitrogen. After the mixture was stirred for 1 h
at room temperature, a solution of anhydrous DMF (2.27 g,
31.1 mmol) in anhydrous diethyl ether (10 mL) was added.
The reaction mixture was stirred for 3 h at room temperature,
poured into a saturated aqueous solution of ammonium
chloride (600 mL), and extracted with diethyl ether (4 × 400
mL). The solvent was removed from the dried extracts to give
the crude product as a brown solid (2.01 g, 10.6 mmol, 67%):
mp 107-109 °C. A sample was purified by recrystallization
to give a pale yellow solid: mp 131-132 °C (H2O) (lit.25 mp
135-136 °C); 1H NMR (CDCl3) δ 9.95 (s, 1 H), 8.69 (d, 2 H, J
) 6.0), 7.79 (d, 1 H, J ) 4.0), 7.56 (d, 1 H, J ) 4.0), 7.53 (d, 2
H, J ) 6.0).
1-[5-(4-P yr id yl)th ien -2-yl]-2-(5-br om oth ien -2-yl)eth yl-
en e (3d ). A suspension of sodium hydride in oil (60% by
weight; 0.29 g corresponding to 0.17 g, 7.2 mmol) was
thoroughly washed with anhydrous THF and finally suspended
in THF (15 mL). A solution of diethyl [(5-bromothien-2-
yl)methyl]phosphonate (2.50 g, 7.99 mmol) (prepared as in the
synthesis of 3c) in THF (10 mL) was first added to this
suspension kept under nitrogen, followed after 10 min by the
addition of a solution of 4-(5-formylthien-2-yl)pyridine (5d )
(1.001 g, 5.28 mmol) in the same solvent (7 mL). The mixture
was cautiously heated in an oil bath at 50 °C until the
evolution of hydrogen had ceased and then at reflux for 2 h.
The mixture was allowed to cool to room temperature, poured
into a saturated aqueous solution of ammonium chloride (80
mL), and extracted with chloroform (4 × 100 mL). The solvent
was removed from the dried extracts to give a brown solid (3.6
1-(4-P yr idyl)-2-(5-br om oth ien -2-yl)eth ylen e (3c). A mix-
ture of 5-bromo-2-(chloromethyl)thiophene55 (4.60 g, 21.76
mmol) and triethyl phosphite (3.60 g, 21.76 mmol) was refluxed
for 6 h at 110 °C. The resulting oil was heated at 200 °C and
1 mmHg in a Kugelrohr apparatus to distill low-boiling
components and leave the diethyl [(5-bromothien-2-yl)meth-
yl]phosphonate (6.02 g, 19.22 mmol, 88%) as a lightly red oily
residue: this was used for subsequent steps without further
purification: 1H NMR (CDCl3) δ 6.88 (d, 1 H, J ) 3.7), 6.71
(tt, 1 H, J (PH) ) 3.7, J ) 1.0), 4.07 (dq, 4 H, J (PH) ) 8.22),
3.26 (dd, 2 H, J (PH) ) 20.7), 1.28 (t, 6 H, J ) 7.1).
A
suspension of sodium hydride in oil (60% by weight; 0.77 g
corresponding to 0.46 g, 19.2 mmol) was thoroughly washed
with anhydrous THF and finally suspended in the same
solvent (50 mL). A solution of diethyl [(5-bromothien-2-
yl)methyl]phosphonate (5.98 g, 19.1 mmol) in anhydrous THF
(20 mL) was first added to this suspension kept under nitrogen,
followed by the addition of a solution of 4-pyridinecarbaldehyde
(2.05 g, 19.1 mmol) in the same solvent (25 mL). The mixture
was cautiously heated in an oil bath at 50 °C until the
evolution of hydrogen had ceased and then at reflux for 1 h.
The mixture was poured onto ice (250 mL) to give a brown
solid (3.08 g) that was collected and washed with H2O. After
drying, sublimation afforded the pure product as a light yellow
solid (2.72 g, 10.22 mmol, 54%): mp 106-107 °C; 1H NMR
(CDCl3) δ 8.54 (d, 2 H, J ) 6.1), 7.27 (d, 2 H, J ) 6.1), 7.27 (d,
1 H, J ) 16.4), 6.97 (d, 1 H, J ) 3.9), 6.87 (d, 1 H, J ) 3.9),
6.68 (d, 1 H, J ) 16.4). Anal. Calcd for C11H8BrNS: C, 49.64;
H, 3.03; N, 5.26. Found: C, 49.87; H, 3.29; N, 5.35.
1-(4-P yr id yl)-2-[5-(d icya n om eth a n id o)th ien -2-yl]eth yl-
en e Sod iu m Sa lt (2c). Malononitrile (0.59 g, 9.00 mmol) was
added to an ice-cooled suspension of sodium hydride (0.72 g,
60% oily, 18.00 mmol) in anhydrous 1,2-dimethoxyethane (30
(55) Gronowitz, S.; Lilijefors, S. Chem. Scr. 1979, 13, 39.

5764 J . Org. Chem., Vol. 62, No. 17, 1997
Abbotto et al.
g), which was submitted to flash chromatography (AcOEt) on
silica gel to provide the product as a yellow solid (1.05 g, 3.02
mmol, 57%): mp 125 °C. An analytical pale yellow sample
was obtained by recrystallization: mp 140 °C (AcOEt); 1H
NMR (CDCl3) δ 8.58 (d, 2 H, J ) 6.0), 7.48 (d, 2 H, J ) 6.0),
7.42 (d, 1 H, J ) 4.7), 7.05 (d, 1 H, J ) 4.7), 6.95 (d, 1 H, J )
3.9), 6.93 (d, 1 H, J ) 15.7), 6.88 (d, 1 H, J ) 15.7), 6.81 (d, 1
H, J ) 3.9). Anal. Calcd for C15H10BrNS2: C, 51.74; H, 2.89;
N, 4.02. Found: C, 51.57; H, 2.99; N, 4.28.
1-[5-(4-P yr id yl)t h ien -2-yl]-2-[5-(d icya n om et h a n id o)-
th ien -2-yl]eth ylen e Sod iu m Sa lt (2d ). A procedure similar
to that used for the synthesis of 1-(4-pyridyl)-2-[5-(dicya-
nomethanido)thien-2-yl]ethylene sodium salt (2c) was em-
ployed. From 1-[5-(4-pyridyl)thien-2-yl]-2-(5-bromothien-2-
yl)ethylene (3d ) (0.505 g, 1.45 mmol), malononitrile (0.190 g,
2.88 mmol), sodium hydride (0.24 g, 60% oily, 5.9 mmol), and
tetrakis(triphenylphosphine)palladium(0) (0.154 g, 0.133 mmol),
the product was obtained as a reddish solid (0.50 g, 1.40 mmol,
97%): mp > 240 °C; this was used for the subsequent step
without further purification; an analytical sample was ob-
tained after washing with H2O and EtOH at room tempera-
ture: 1H NMR (DMSO-d6) δ 8.51 (d, 2 H, J ) 6.2), 7.68 (d,
1H, J ) 3.9), 7.55 (d, 2 H, J ) 6.2), 7.07 (d, 1 H, J ) 3.9), 7.02
(d, 1 H, J ) 14.6), 6.84 (d, 1 H, J ) 3.7), 6.53 (d, 1 H, J )
15.6), 6.00 (d, 1 H, J ) 3.7). Anal. Calcd for C18H10N3S2Na‚
1/3H2O: C, 59.82; H, 2.97; N, 11.63. Found: C, 59.97; H, 2.98;
N, 11.87.
1-[5-(4-N -Me t h ylp yr id in iu m )t h ie n -2-yl]-2-[5-(d icy-
a n om eth a n id o)th ien -2-yl]eth ylen e (1d ). A procedure simi-
lar to that used for the synthesis of 2-(4-N-methylpyridinium)-
5-(dicyanomethanido)thiophene (1a ) was employed. From the
sodium salt 2d (0.518 g, 1.46 mmol) and methyl triflate (0.239
g, 1.457 mmol) was obtained the title product as a dark brown-
violet solid (0.301 g, 0.866 mmol, 59%): mp > 240 °C. A pure
analytical sample was obtained by recrystallization from
EtOH/DMF: 1H NMR (DMSO-d6) δ 8.68 (d, 2 H, J ) 7.5), 8.11
(d, 1 H, J ) 3.5), 8.08 (d, 2 H, J ) 7.5), 7.24 (d, 1 H, J ) 3.5),
7.22 (d, 1 H, J ) 16.0), 6.95 (d, 1 H, J ) 4.3), 6.58 (d, 1 H, J
) 16.1), 6.06 (d, 1 H, J ) 4.3), 4.30 (s, 3 H). Anal. Calcd for
C19H13N3S2: C, 65.69; H, 3.77; N, 12.10. Found: C, 66.06; H,
3.70; N, 11.98.
1-(4-P yr idyl)-2-(2-th ien yl)eth ylen e (6). A procedure simi-
lar to that used for the synthesis of 1-[5-(4-pyridyl)thien-2-
yl]-2-(5-bromothien-2-yl)ethylene (3d ) was employed. From
diethyl (2-thienylmethyl)phosphonate56 (2.001 g, 8.54 mmol),
4-pyridinecarbaldehyde (1.002 g, 9.35 mmol), and sodium
hydride (0.56 g, 60% oily, 14.1 mmol) was obtained the
practically pure product as a yellow solid (1.50 g, 8.01 mmol,
94%): mp 143-145 °C. An analytical sample was purified by
recrystallization: mp 145-147 °C (benzene) (lit.26 mp 151-
151.5 °C); 1H NMR (CDCl3) δ 8.54 (d, 2 H, J ) 5), 7.41 (d, 1 H,
J ) 16.1), 7.29 (d, 2 H, J ) 5), 7.27 (d, 1 H, J ) 5.1), 7.14 (d,
1 H, J ) 3.7), 7.00 (dd, 1 H, J ) 5.0, 3.6), 6.81 (d, 1 H, J )
16.1). Anal. Calcd for C11H9NS: C, 70.6; H, 4.8; N, 7.5.
Found: C, 70.8; H, 4.5; N, 7.2.
bromothien-2-yl)methyl]phosphonate (2.30 g, 7.35 mmol) in
THF (10 mL) was first added to this suspension kept under
nitrogen, followed after 10 min by the addition of a solution
of 1-(4-pyridyl)-2-(5-formylthien-2-yl)ethylene (5e) (1.35 g, 6.27
mmol) in the same solvent (10 mL). The obtained very dark
mixture was refluxed for 2 h, cooled to room temperature, and
then poured into a saturated aqueous solution of ammonium
chloride (120 mL). The brown precipitate was collected to give
the product (1.59 g, 4.25 mmol, 68%): mp 135-140 °C. An
analytical yellow sample was obtained by recrystallization: mp
142 °C (i-PrOH); 1H NMR (CDCl3) δ 8.55 (d, 2 H, J ) 6), 7.35
(d, 1 H, J ) 16.0), 7.30 (m, 3 H), 7.02 (d, 1 H, J ) 3.8), 6.98 (d,
1 H, J ) 18.8), 6.95 (d, 1 H, J ) 3.8), 6.90 (d, 1 H, J ) 5.8),
6.77 (d, 1 H, J ) 18.6), 6.76 (d, 1 H, J ) 16.0). Anal. Calcd
for C17H12BrNS2: C, 54.55; H, 3.23; N, 3.74. Found: C, 54.65;
H, 3.47; N, 3.66.
1-[5-[1-(4-P yr id yl)e t h e n -2-yl]t h ie n -2-yl]-2-[5-(d icy-
a n om eth a n id o)th ien -2-yl]eth ylen e Sod iu m Sa lt (2e). A
procedure similar to that used for the synthesis of 1-(4-pyridyl)-
2-[5-(dicyanomethanide)thien-2-yl]ethylene sodium salt (2c)
was employed. From 1-[5-[1-(4-pyridyl)ethen-2-yl]thien-2-yl]-
2-(5-bromothien-2-yl)ethylene (3e) (0.300 g, 0.802 mmol),
malononitrile (0.107 g, 1.60 mmol), sodium hydride (0.13 g,
60% oily, 3.3 mmol), and tetrakis(triphenylphosphine)pal-
ladium(0) (0.092 g, 0.080 mmol) was obtained the title product
as a reddish solid (0.295 g, 0.774 mmol, 97%): mp > 240 °C.
This was used for subsequent step without further purifica-
tion: 1H NMR (DMSO-d6) δ 8.49 (d, 2 H, J ) 5.9), 7.67 (d, 1
H, J ) 16.0), 7.49 (d, 2 H, J ) 6.1), 7.15 (d, 1 H, J ) 3.8), 6.97
(d, 1 H, J ) 3.9), 6.95 (d, 1 H, J ) 15.5), 6.84 (d, 1 H, J ) 3.8),
6.75 (d, 1 H, J ) 16.0), 6.51 (d, 1 H, J ) 15.6), 5.99 (d, 1 H, J
) 3.8).
1-[5-[1-(4-N-Meth ylp yr id in iu m )eth en -2-yl]th ien -2-yl]-
2-[5-(d icya n om eth a n id o)th ien -2-yl]eth ylen e (1e). A pro-
cedure similar to that used for the synthesis of 2-(4-N-
methylpyridinium)-5-(dicyanomethanido)thiophene (1a ) was
employed. From the sodium salt 2e (0.416 g, 1.09 mmol) and
methyl triflate (0.178 g, 1.09 mmol) was obtained the title
product as a brown-reddish solid (0.33 g, 0.88 mmol, 81%): mp
1
> 240 °C; H NMR (DMSO-d6) δ 8.71 (d, 2 H, J ) 6.3), 8.11
(d, 1 H, J ) 16.3), 8.07 (d, 2 H, J ) 6.9), 7.35 (d, 1 H, 3.8), 7.07
(d, 1 H, J ) 3.8), 7.06 (d, 1 H, J ) 15.4), 6.93 (d, 1 H, J )
16.2), 6.90 (d, 1 H, J ) 3.8), 6.55 (d, 1 H, J ) 15.5), 6.04 (d, 1
H, J ) 3.8), 4.20 (s, 3 H); HRMS m/ z calcd for C21H15N3S2
373.0707, found 373.0721.
5-(4-P yr id yl)-2,2′:5′,2′′-ter th iop h en e (7). A solution of
5-(2,2′-bithienyl)magnesium bromide in anhydrous diethyl
ether (25 mL), prepared from 5-bromo-2,2′-bithiophene (1.40
g, 5.81 mmol) and magnesium (0.28 g, 11.5 mmol) as described
in the synthesis of 4-[5-(2-thienyl)thien-2-yl]pyridine (4b), was
added dropwise to a stirred suspension of 4-(5-bromothien-2-
yl)pyridine (3a ) (1.22 g, 5.00 mmol) and PdCl2(dppf) (0.04 g,
0.05 mmol) in the same solvent (25 mL) at room temperature.
After being stirred overnight at room temperature, the reaction
mixture was poured into a saturated aqueous ammonium
chloride solution (100 mL), and the resulting precipitate was
collected by filtration and washed with diethyl ether to give
the product as a yellow solid (2.48 g, 7.62 mmol, 66%): mp
239 °C (EtOH/DMF); 1H NMR (CDCl3) δ 8.57 (d, 2 H, J ) 6.1),
7.46 (d, 2 H, J ) 6.1), 7.44 (d, 1 H, J ) 3.9), 7.24 (d, 1 H, J )
4.9), 7.19 (d, 1 H, J ) 3.6), 7.18 (d, 1 H, J ) 3.9), 7.15 (d, 1 H,
J ) 3.8), 7.10 (d, 1 H, J ) 3.8), 7.03 (dd, 1 H, J ) 4.9, 3.6).
Anal. Calcd for C17H11NS3: C, 62.73; H, 3.41; N, 4.30.
Found: C, 62.62; H, 3.25; N, 4.24.
1-(4-P yr idyl)-2-(5-for m ylth ien -2-yl)eth ylen e (5e). A pro-
cedure similar to that used for the synthesis of 4-(5-formylth-
ien-2-yl)pyridine (5d ) was employed. From diisopropylamine
(0.816 g, 8.01 mmol), n-BuLi 1.6 M in hexane (5 mL, 8.0 mmol),
1-(4-pyridyl)-2-(2-thienyl)ethylene (6) (0.998 g, 5.33 mmol), and
anhydrous DMF (0.816 g, 11.2 mmol) was obtained the crude
title product as a brownish solid (0.750 g, 3.48 mmol, 65%):
mp 97-98 °C. This was used without further purification in
the next step. A pure analytical yellow sample was obtained
by recrystallization from i-PrOH and sublimation (90 °C/0.01
5-(4-P yr id yl)-5′′-br om o-2,2′:5′,2′′-ter th iop h en e (8).
A
1
mmHg): mp 98 °C; H NMR (CDCl3) δ 9.90 (s, 1 H), 8.56 (d,
solution of N-bromosuccinimide (0.73 g, 4.1 mmol) in anhy-
drous DMF (50 mL) was added dropwise to a suspension of
5-(4-pyridyl)-2,2′:5′,2′′-terthiophene (7) (1.20 g, 3.7 mmol) in
the same solvent (70 mL) under nitrogen in the dark. After
being stirred overnight at room temperature, keeping the
reaction flask removed from light, the mixture was poured onto
ice (120 mL) and the resulting precipitate collected by filtra-
tion, giving the product as a solid (0.90 g, 2.2 mmol, 61%): mp
2 H, J ) 6.2), 7.67 (d, 1 H, J ) 4.0), 7.38 (d, 1 H, J ) 16.1),
7.33 (d, 2 H, J ) 6.2), 7.22 (d, 1 H, J ) 4.0), 7.01 (d, 1 H, J )
16.0). Anal. Calcd for C12H9NOS: C, 66.94; H, 4.21; N, 6.51.
Found: C, 66.83; H, 4.16; N, 6.49.
1-[5-[1-(4-P yr idyl)eth en -2-yl]th ien -2-yl]-2-(5-br om oth ien -
2-yl)eth ylen e (3e). A suspension of sodium hydride in oil
(0.370 g, 60% oily, 9.25 mmol) was suspended in anhydrous
THF (25 mL) under nitrogen. A solution of diethyl [(5-
1
240 °C (EtOH/DMF); H NMR (DMSO-d6) δ 8.64-8.52 (m, 2
H), 7.79 (d, 1 H, J ) 3.9), 7.67-7.61 (m, 2 H), 7.45 (d, 1 H, J
) 3.9), 7.39 (d, 1 H, J ) 3.8), 7.31 (d, 1 H, J ) 3.8), 7.23 (d, 1
H, J ) 3.0), 7.21 (d, 1 H, J ) 3.0). Anal. Calcd for
(56) Kellogg, R. M.; Groen, M. B.; Wynberg, H. J . Org. Chem. 1967,
32, 3093.

Synthesis of N-Alkylpyridinium Dicyanomethanides
J . Org. Chem., Vol. 62, No. 17, 1997 5765
C17H10BrNS3: C, 50.49; H, 2.50; N, 3.46. Found: C, 50.22; H,
2.53; N, 3.68.
N-Meth yl-4-(2-th ien yl)pyr idin iu m Tr iflate (15a). Meth-
yl triflate (67.8 mL, 0.101 g, 0.62 mmol) was added to a
solution of 4-(2-thienyl)pyridine (4a ) (0.100 g, 0.62 mmol) in
dry acetone (1.5 mL) at room temperature. After the mixture
was stirred overnight, the solvent was removed under reduced
pressure to leave a solid that was taken up with dry diethyl
ether (3 mL). The resulting solid was separated by filtration
to give the practically pure product as a yellow solid (0.053 g,
2-Br om o-3-octylth iop h en e (9). A solution of N-bromo-
succinimide (9.06 g, 50.9 mmol) in anhydrous DMF (40 mL)
was added dropwise to a solution of 3-octylthiophene57 (9.00
g, 45.8 mmol) in the same solvent (40 mL) under nitrogen in
the dark. After being stirred for 2 h at room temperature,
keeping the reaction flask repaired from light, the mixture was
poured onto ice (100 mL) and extracted with diethyl ether (3
× 100 mL). The combined organic layers were washed with
H2O, dried, and evaporated to dryness to leave a yellowish oil
(11.6 g), which was submitted to flash chromatography (CH3CN)
on RP-18 solid phase. The title product was obtained as a
colorless oil57 (9.99 g, 36.3 mmol, 79%): 1H NMR (CDCl3) δ
7.18 (d, 1 H, J ) 5.7), 6.79 (d, 1 H, J ) 5.7), 2.56 (t, 2 H, J )
7.5), 1.58-1.50 (m, 2 H), 1.34-1.21 (m, 10 H), 0.89 (t, 3 H, J
) 4.5).
1
0.16 mmol, 26%): mp ) 135 °C (i-PrOH); H NMR (DMSO-
d6) δ 8.85 (d, 2 H, J ) 6.8), 8.35 (d, 2 H, J ) 6.8), 8.23 (d, 1 H,
J ) 3.9), 8.01 (d, 1 H, J ) 5.0), 7.39 (dd, 1 H, J ) 5.0, 3.9),
4.26 (s, 3 H). Anal. Calcd for C11H10NS2F3O3‚1/2H2O: C,
39.52; H, 3.32; N, 4.19. Found: C, 39.86; H, 3.12; N, 4.60.
2-Cya n o-2-p h en ylp r op ion on itr ile (16). A solution of
phenylmalononitrile29 (0.088 g, 0.62 mmol) in dry acetone (1.5
mL) was added to a suspension of K2CO3 in the same solvent
(2 mL). After the mixture was stirred for 10 min, methyl
iodide (46.3 mL, 0.106 g, 0.74 mmol) was added. After the
resulting mixture was stirred overnight at room temperature,
K2CO3 solid was discarded, and the filtered solution was
evaporated to dryness to leave a residue that was taken up
with diethyl ether (6 mL). From the filtered solution, the
solvent was removed and the residue submitted to distillation
under reduced pressure to give the pure product (0.084 g, 0.53
5-(4-P yr id yl)-3′′-octyl-2,2′:5′,2′′-ter th iop h en e (10). A so-
lution of 2-bromo-3-octylthiophene (9) (0.95 g, 3.4 mmol) in
anhydrous diethyl ether (7 mL) was added dropwise to a
suspension of magnesium (0.17 g, 6.9 mmol) and 1,2-dibro-
moethane (8 µL) in the same solvent (10 mL), while the flask
was kept under nitrogen dipped in a ultrasound bath main-
tained at 30 °C. After 20 min in the ultrasound bath, the
obtained Grignard solution was added dropwise to a stirred
suspension of 4-[[5-(5-bromothien-2-yl)]thien-2-yl]pyridine (3b)
(1.00 g, 3.10 mmol) and PdCl2(dppf) (0.02 g, 0.03 mmol) in
anhydrous diethyl ether (15 mL) under nitrogen at room
temperature. After being stirred for 5 h at room temperature,
the reaction mixture was poured into a saturated aqueous
ammonium chloride solution (30 mL), and the aqueous layer
was extracted with methylene chloride (3 × 30 mL). The
combined organic layers were washed with H2O and dried and
the solvent evaporated to leave a solid (1.83 g), which was
submitted to flash chromatography (diethyl ether) on silica gel.
The title product was obtained as a yellow solid (0.93 g, 2.1
1
mmol, 87%): bp ) 60 °C/0.02 mmHg); H NMR (DMSO-d6) δ
7.69-7.64 (m, 2 H), 7.61-7.50 (m, 3 H), 2.19 (s, 3 H). Anal.
Calcd for C10H8N2: C, 76.90; H, 5.16; N, 17.94. Found: C,
76.58; H, 5.12; N, 17.76.
In ter m olecu la r Com p etitive Rea ction w ith Meth yl
Tr ifla te or Meth yl Iod id e. A solution of MeONa (0.033 g,
0.62 mmol) (freshly prepared from sodium turnings and
absolute MeOH) in absolute MeOH (1 mL) was added to a
solution of phenylmalononitrile29 (0.088 g, 0.62 mmol) in the
same solvent (1 mL). After the mixture was stirred for 15 min,
the solvent was removed under reduced pressure to give
phenylmalononitrile sodium salt (14) as a light yellow solid:
1H NMR (DMSO-d6) δ 6.99 (t, 2 H, J ) 7.8), 6.70 (d, 2 H, J )
7.9), 6.48 (t, 1 H, J ) 7.4). Dry acetone (1 mL) was added to
the solid 14 and the obtained solution mixed with a solution
of 4-(2-thienyl)pyridine (4a ) (0.100 g, 0.62 mmol) in dry acetone
(1 mL). Methyl triflate (67.8 mL, 0.101 g, 0.62 mmol) was
added in five equivalent portions every 15 min at room
temperature. After 1 h, a sample was evaporated to dryness
1
mmol, 68%): mp 88 °C (EtOH); H NMR (CDCl3) δ 8.60 (d, 2
H, J ) 6.1), 7.45 (d, 2 H, J ) 6.1), 7.42 (d, 1 H, J ) 3.9), 7.18
(d, 1 H, J ) 5.6), 7.12 (d, 1 H, J ) 3.9), 7.01 (d, 1 H, J ) 3.9),
6.98 (d, 1 H, J ) 3.9), 6.79 (d, 1 H, J ) 5.6), 2.55 (t, 2 H, J )
7.8), 1.65-1.45 (m, 2 H), 1.40-1.15 (m, 10 H), 0.85 (t, 3 H, J
) 7.1). Anal. Calcd for C25H27NS3: C, 68.59; H, 6.23; N, 3.20.
Found: C, 68.65; H, 6.05; N, 3.31.
5-(4-P y r id y l)-5′′-b r o m o -3′′-o c t y l-2,2′:5′,2′′-t e r t h io -
p h en e (11). A solution of N-bromosuccinimide (0.339 g, 1.90
mmol) in anhydrous DMF (6 mL) was added dropwise to a
stirred suspension of 5-(4-pyridyl)-3′′-octyl-2,2′:5′,2′′-terthiophene
(10) (0.750 g, 1.71 mmol) in the same solvent (6 mL) under
nitrogen in the dark. After being stirred for 4 h at room
temperature, keeping the reaction flask removed from light,
the mixture was poured onto ice (12 mL), and the resulting
precipitate was collected by filtration to give the product as
an orange solid (0.866 g, 1.68 mmol, 98%): mp 170 °C (EtOH);
1H NMR (CDCl3) δ 8.58 (d, 2 H, J ) 4.8), 7.61 (d, 2 H, J )
4.8), 7.54 (d, 1 H, J ) 3.9), 7.24 (d, 1 H, J ) 3.9), 7.22 (d, 1 H,
J ) 3.8), 7.01 (d, 1 H, J ) 3.8), 6.91 (s, 1 H), 2.70 (t, 2 H, J )
7.8), 1.70-1.50 (m, 2 H), 1.45-1.20 (m, 10 H), 0.90 (t, 3 H, J
) 7.1). Anal. Calcd for C25H26BrNS3: C, 58.12; H, 5.08; N,
2.71. Found: C, 58.26; H, 4.95; N, 2.55.
5-(4-P yr id yl)-5′′-d icya n om et h a n id e-3′′-oct yl-2,2′:5′,2′′-
ter th iop h en e Sod iu m Sa lt (12). A procedure similar to that
used for the synthesis of the sodium salt (2c) was employed.
From 5-(4-pyridyl)-5′′-bromo-3′′-octyl-2,2′:5′,2′′-terthiophene
(11) (0.780 g, 1.51 mmol), malononitrile (0.264 g, 3.99 mmol),
sodium hydride (0.32 g, 60% oily, 8.0 mmol), and tetraki-
s(triphenylphosphine)palladium(0) (0.179 g, 0.16 mmol) was
obtained the title product as a reddish solid (0.617 g, 1.18
mmol, 78%): mp > 240 °C (EtOH); 1H NMR (DMSO-d6) δ 8.56
(d, 2 H, J ) 6.1), 7.78 (d, 1 H, J ) 3.9), 7.62 (d, 2 H, J ) 6.1),
7.33 (d, 1 H, J ) 3.9), 7.30 (d, 1 H, J ) 3.9), 6.82 (d, 1 H, J )
3.9), 5.97 (s, 1 H), 2.55 (t, 2 H, J ) 7.8), 1.65-1.48 (m, 2 H),
1.40-1.15 (m, 10 H), 0.82 (t, 3 H, J ) 7.1). Anal. Calcd for
C28H26N3S3Na: C, 64.20; H, 5.01; N, 8.02. Found: C, 63.98;
H, 5.46; N, 7.63.
1
and the solid analyzed by H NMR (DMSO-d6). The relative
ratio of N-methyl-4-(2-thienyl)pyridinium triflate (15a ) and
2-cyano-2-phenylpropiononitrile (16) was determined by com-
parison with the spectra of the pure compounds. The same
procedure and molar quantities were used in the reaction with
methyl iodide.
2-(4-1H -P y r i d i n i u m )-5-(d i c y a n o m e t h a n i d o )t h i o -
p h en e (17). Aqueous HCl (10%) was added dropwise to a
solution of 4-[5-(dicyanomethanido)thien-2-yl]pyridine sodium
salt (2a ) (0.050 g, 0.20 mmol) in H2O (3 mL) until pH 1 was
reached. A violet precipitate was readily obtained. After being
stirred for 15 min at room temperature, the precipitate was
collected, washed with H2O (1 mL), and dried under reduced
pressure at 60 °C to give the practically pure product (0.026
1
g, 0.11 mmol, 55%) as a violet solid: mp > 240 °C (DMF); H
NMR (DMSO-d6) δ 13.8 (broad, 1 H), 8.25 (d, 2 H, J ) 6.8),
7.92 (d, 1 H, J ) 4.4), 7.56 (d, 2 H, J ) 6.8), 6.39 (d, 1 H, J )
4.4). Anal. Calcd for C12H7N3S: C, 63.98; H, 3.13; N, 18.65.
Found: C, 63.48; H, 3.29; N, 18.38.
Ack n ow led gm en t. We are grateful to Prof. Antonio
Selva for providing HRMS data.
Su p p or tin g In for m a tion Ava ila ble: Copies of the 1H
NMR (DMSO-d6) spectrum (full and aromatic region) of
compound 1e (2 pages). This material is contained in libraries
on microfiche, immediately follows this article in the microfilm
version of the journal, and can be ordered from the ACS; see
any current masthead page for ordering information.
(57) McCullough, R. D.; Lowe, R. D.; J ayaraman, M.; Anderson, D.
L. J . Org. Chem. 1993, 58, 904-912.
J O970059X