Iminium salts of ω-dithiafulvenylpolyenals: An easy entry to the corresponding aldehydes and doubly proaromatic nonlinear optic-phores

Article abstract of DOI:10.1021/jo800801q

(Chemical Equation Presented) A short, high-yielding route to u-difhiafulvenylpolyenals (1) via the corresponding iminium salts (2) and starting from trimethyl-1,3-dithiolium tetrafluoroborate is reported. The Knoevenagel reactions of either 1 or 2 with isoxazolone-containing acceptors afford merocyanines 7 and 9, in a process that is often accompanied by a vinylene-shortening side reaction. Experimental and theoretical studies reveal that compounds 7 and 9, featuring two proaromatic end groups, are strongly polarized and show good second-order nonlinear optical responses.

Full text of DOI:10.1021/jo800801q

Iminium Salts of ω-Dithiafulvenylpolyenals: An Easy Entry to the
Corresponding Aldehydes and Doubly Proaromatic Nonlinear
Optic-phores
Silvia Al´ıas,† Raquel Andreu,† Mar´ıa Jesu´s Blesa,† Miguel Angel Cerda´n,†
Santiago Franco,† Javier Gar´ın,*,† Carolina Lo´pez,† Jesu´s Orduna,† Jorge Sanz,†
Raquel Alicante,‡ Bele´n Villacampa,‡ and Magali Allain§
Departamento de Qu´ımica Orga´nica, ICMA, UniVersidad de Zaragoza-CSIC,
50009 Zaragoza, Spain, Departamento de F´ısica de la Materia Condensada, ICMA, UniVersidad de
Zaragoza-CSIC, 50009 Zaragoza, Spain, and Laboratoire de Chimie, Inge´nierie Moleculaire et Mate´riaux
d’Angers (UMR CNRS 6200), UniVersite´ d’Angers, 2, BouleVard LaVoisier, 49045-Angers Cedex, France
jgarin@unizar.es
ReceiVed April 10, 2008
A short, high-yielding route to ω-dithiafulvenylpolyenals (1) via the corresponding iminium salts (2)
and starting from trimethyl-1,3-dithiolium tetrafluoroborate is reported. The Knoevenagel reactions of
either 1 or 2 with isoxazolone-containing acceptors afford merocyanines 7 and 9, in a process that is
often accompanied by a vinylene-shortening side reaction. Experimental and theoretical studies reveal
that compounds 7 and 9, featuring two proaromatic end groups, are strongly polarized and show good
second-order nonlinear optical responses.
Introduction
revealed that molecules with strong, low energy intramolecular
charge transfer (ICT) transitions were good candidates for
second-order NLO studies. The ground state and the first excited
state of such molecules can be represented as linear combina-
tions of neutral and zwitterionic (charge-separated) limiting
forms, and their contributions can be estimated through the use
of structural parameters, prominent among which is bond length
alternation (BLA), defined as the difference between the average
carbon-carbon single and double bond lengths in the polyme-
thine backbone. Therefore, BLA essentially represents the degree
of delocalization of the π-bridge and was found to peak at values
of ca. (0.05 Å.1b,2
Not only donor and acceptor strengths but also the nature of
the π-spacer has a marked effect on BLA (and, therefore, on
ꢀ).3 The limited thermal and photochemical stability of long
polyenic chains has led to the introduction of aromatic spacers,
but this structural modification usually gives rise to less
Conjugated donor-acceptor (D-π-A) compounds are being
actively investigated for their second-order nonlinear optical
(NLO) properties and their applications in telecommunications
and optical information processing. Their microscopic NLO
efficiencies, characterized by their first molecular hyperpolar-
izabilities (ꢀ), depend on the subtle interplay between several
factors, such as the strength of the end groups and the
connectivity of the π-electron bridge, and the successful design
of such NLO-phores relies on the understanding of structure/
NLO relationships,1 many of which were already established
in the 1990s. Extensive use of the “two-level” model soon
† Departamento de Qu´ımica Orga´nica, Universidad de Zaragoza.
‡ Departamento de F´ısica de la Materia Condensada, Universidad de Zaragoza.
§ Laboratoire de Chimie, Inge´nierie Moleculaire et Mate´riaux d’Angers,
Universite´ d’Angers.
(1) (a) Nonlinear Optics of Organic Molecules and Polymers; Nalwa, H. S.,
; Miyata, S., Eds.; CRC Press: Boca Raton, 1997. (b) Marder, S. R.; Kippelen,
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Chem. ReV. 2006, 75, 457–496. (f) Barlow, S.; Marder, S. R. Nonlinear Optical
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10.1021/jo800801q CCC: $40.75 2008 American Chemical Society
Published on Web 07/09/2008

Iminium Salts of ω-DithiafulVenylpolyenals
delocalized structures with decreased NLO responses, since the
ICT excitation decreases the resonance energy of these mol-
ecules on passing from an aromatic ground-state to a quinoid-
like excited state. To overcome this tradeoff, Marder advocated
the use of fragments gaining aromaticity on charge transfer,4
and since then, this strategy has been applied to proaromatic
electron acceptors,5 electron donors,6 and spacers.7
Isoxazolones are powerful proaromatic acceptors that have
afforded high nonlinearities when linked to aromatic donors,
such as N,N-disubstituted anilines8 and indoles,9 but NLO-phores
featuring an isoxazolone and a proaromatic donor have received
only a scant attention.10
As the proaromatic character of 1,4-dithiafulvenes has given
rise to efficient NLO-phores,7,11 in this paper we report the
synthesis, structural, and optical properties of merocyanines 7
and their ring-locked analogues 9, which are expected to benefit
from the gain in aromaticity at both end groups upon photo-
excitation.
and extended tetrathiafulvalenes)12 from the newly prepared
iminium salts 2b,c, and report an unexpected vinylene shortening
reaction of merocyanines, a process that remains nearly un-
noticed in the literature.
Results and Discussion
Synthesis and Hydrolysis of Iminium Salts 2b and 2c:
A New Access to Aldehydes 1b and 1c. The reaction of
vinylogous tertiary formamides with acylating agents such
as acetic anhydride or acetyl halides generates the corre-
sponding O-acetyl derivatives (ω-acetoxyiminium salts)13
which are strongly electrophilic. Nevertheless, the potential
synthetic utility of such species remains largely unexplored.
In particular, there are very few examples of their reactions
with heteroaromatic cations bearing activated methyl groups,
which show nucleophilic properties through the corresponding
methylene bases (anhydrobases).14 We have found that the
reaction of the easily prepared trimethyl-1,3-dithiolium
tetrafluoroborate 315 with 3-dimethylaminoacrolein in Ac2O
at room temperature gives salt 2b (vinylogous of 2a)15 in
excellent yield (94%) (Scheme 1).
On the other hand, the reaction of 3 with 516 affords a 3:1
mixture of 2c and N,N-dimethyl-5-acetoxypentadienyliden-
1
iminium tetrafluoroborate (identified by H NMR and mass
spectrometry). Isolation of pure 2c from this mixture was
troublesome, but this problem was easily circumvented
through hydrolysis (see below) of the crude product to afford
aldehyde 1c (55% yield) and reaction of the latter with
dimethylammonium tetrafluoroborate,17 affording 2c in 92%
yield (Scheme 1).
It is unfortunate that, contrary to 2-methylbenzothiazolium
salts,18 the reaction of 3 with glutaconaldehyde dianilide
hydrochloride does not take place to any appreciable extent,
since this reaction would give rise to the anilino analogue of
2c in a single step and from a commercially available reagent.
A related failure, involving the reaction of a 2-methylene-1,3-
dithiole derivative with malonaldehyde dianilide hydrochloride,
has also been reported.19
Moreover, we describe a very simple synthesis of aldehydes
1b,c (widely used for the preparation of D-π-A compounds
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If desired, 2b can be easily hydrolyzed to aldehyde 1b in
good yield (79%) (Scheme 1). The only reported synthesis of
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J. Org. Chem. Vol. 73, No. 15, 2008 5891

Al´ıas et al.
SCHEME 1
1b is a four-step procedure (overall yield ca. 40%) which
involves in the key step the reaction of diethyl 4,5-dimethyl-
1,3-dithiol-2-ylphosphonate with fumaraldehyde mono(dimethyl
acetal),20 prepared in turn from furan.21 Therefore, the two-
step synthesis of 1b from 3 herein reported constitutes a simpler,
improved procedure, with an overall yield of 74%. We also want
to point out that our attempts to prepare 1b by vinylogation of
the easily available 1a22 with a variety of reagents (A-F)23–27
did not meet with success.
a comparative study of the reactivity of 1 and 2 toward
isoxazolone-containing acceptors 6 and 8.
The reaction of 6 with aldehydes 1a and 1b (Scheme 2)
affords targets 7a (94%) and 7b (74%), and similar yields are
obtained from the reactions of 6 with the corresponding iminium
salts 2a and 2b (7a, 91%; 7b, 62%).
On the other hand, compound 7c could only be isolated from
the reaction of 6 with 2c, since the corresponding aldehyde 1c
only afforded a complex mixture. It is worth mentioning that
even when smooth conditions (absence of base, ice-bath
temperature) are used, the reaction of 2c with 6 affords 7c
together with a small amount of the unexpected product 7b. In
fact, when this reaction is carried out in the presence of base at
room temperature, 7b becomes the major product. Some aspects
of this chain-shortening reaction are discussed below.
With a view to study the effect that ring-locking of the π-spacer
has on the optical and thermal properties of the corresponding
merocyanines, we also decided to study the reactivity of ac-
ceptor 8.
Compound 8 was prepared as previously described,29 since
an alternative procedure30 did not lead in our hands to the
desired compound. As expected,8b 8 was obtained as a Z/E
mixture (10:3 ratio). Recrystallization from methanol afforded
the (Z)-isomer nearly free from the (E)-isomer (ca. 10:1 ratio).
According to the expected weaker acidity of 8 when compared
to 6 (pKa ) 4.0),31 we have found that its reactions with either
1 or 2 only take place in the presence of a base (Scheme 3).
The enhanced reactivity of iminium salts 2, compared to that
of aldehydes 1, is demonstrated by the much higher yield of 9a
when prepared from 2a (45%) than when synthesized from 1a
using piperidine in refluxing ethanol (9%).
Similarly, only the reactions of iminium salts 2b,c with 8
led to the isolation of the desired products 9b,c in synthetically
useful yields, although the corresponding “degraded” merocya-
nines (9a and 9b, respectively) were also formed as byproducts.
On the other hand, this side reaction became dominant when
using aldehydes 1b,c as starting materials, and therefore, this
route was abandoned.
In a similar way, the synthesis of 1c from 3 in 55% yield
(Scheme 1) compares favorably to the previously reported
syntheses of this compound, involving either vinylogation of
1b (23% yield)20 or reaction of 4,5-dimethyl-1,3-dithiol-2-
ylidenetributylphosphorane with (E,E)-mucondialdehyde, also
available from furan (overall yield, 28%).11c
Synthesis of Isoxazolone-Containing Merocyanines 7
and 9. Besides giving rise to the corresponding aldehydes,
iminium salts 2 are also expected to behave as surrogate
aldehydes of enhanced electrophilicity in Knoevenagel-type
reactions.28 To confirm these expectations, we have carried out
(20) Nguyen, T.-T.; Gouriou, Y.; Salle´, M.; Fre`re, P.; Jubault, M.; Gorgues,
A.; Toupet, L.; Riou, A. Bull. Soc. Chim. Fr. 1996, 133, 301–308.
(21) Gre´e, R.; Tourbah, H.; Carrie´, R. Tetrahedron Lett. 1986, 27, 4983–
4986.
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S.; Yoshida, Z.; Kobayashi, T.; Anzai, H. Chem. Mater. 1989, 1, 535–547.
(23) Takahashi, H.; Fujiwara, K.; Ohta, M. Bull. Chem. Soc. Jpn. 1962, 35,
1498–1500.
For the sake of comparison, compound 9d was also synthe-
sized, starting from dithiolium salt 10 (prepared following a
(24) Friese, A.; Hell-Momeni, K.; Zu¨ndorf, I.; Winckler, T.; Dingermann,
T.; Dannhardt, G. J. Med. Chem. 2002, 45, 1535–1542.
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Thozet, A.; Collet, A. Chem. Mater. 1996, 8, 890–906.
(29) Brooker, L. G. S.; Craig, A. C.; Heseltine, D. W.; Jenkins, P. W.;
Lincoln, L. L. J. Am. Chem. Soc. 1965, 87, 2443–2450.
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(b) Al´ıas, S.; Andreu, R.; Cerda´n, M. A.; Franco, S.; Gar´ın, J.; Orduna, J.;
Romero, P.; Villacampa, B. Tetrahedron Lett. 2007, 48, 6539–6542.
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5892 J. Org. Chem. Vol. 73, No. 15, 2008

Iminium Salts of ω-DithiafulVenylpolyenals
SCHEME 2
ing of cyanines was described a long time ago.36 It is well-
known that cyanines and merocyanines show electrophilic
properties at the odd-numbered carbon atoms of the polymethine
chain and, therefore, they can be attacked by nucleophiles at
these atoms.37 This process can trigger the observed degradation
reactions, which can take place either on the final, expected
merocyanines or on the starting iminium salts.
SCHEME 3
To clarify some of these aspects, we have chosen 2b and 7b
as model compounds and have carried out a series of experi-
ments, monitored by TLC, HPLC, MS, and comparison with
authentic samples, which have revealed the following facts:
The expected merocyanine can undergo degradation under
the reaction conditions, since treatment of 7b with 6/piperidine
(DMF, rt, 4.5 h) gives 7a as the major product. On the other
hand, in the absence of piperidine only trace amounts of 7a are
formed.
The degradation of the starting iminium salt occurs to a much
lesser extent, since treatment of 2b with piperidine (DMF, rt,
13 h), followed by basic hydrolysis, affords 1b along with only
a minor amount of aldehyde 1a. This result is not very
surprising, taking into account that the N-linked carbon atom
of the iminium salt carries the highest positive charge along
the chain and that it has been demonstrated that both hard and
soft nucleophiles show a marked preference for the attack at
the terminal carbon atoms of cyanines.38
Therefore, although chain shortening of the iminium salts
cannot be completely ruled out, attack on the initially formed
merocyanines seems to be the main pathway leading to the
degraded products. But, what is the actual nucleophile? Dim-
ethylamine, generated in the Knoevenagel reactions of salts 2,
could play this role, since it is known to degrade cyanines.39
Nevertheless, the reaction of 2b with 6 in the absence of base
does not give rise to chain shortening, and therefore, the liberated
Me2NH does not seem to lie at the origin of the unexpected
reaction. Piperidine seemed an obvious candidate, since it was
reported to be very active at degrading cyanines36a and we have
observed that the reaction of 2b with 6 in the presence of
general method)32 and using conditions analogous to those
reported for related derivatives.11d,33
It has to be mentioned that in every case compounds 9 are
formed as ca. 1:1 (Z)/(E) mixtures around the exocyclic
isoxazolone CdC bond, even when nearly pure (Z)-8 is used
as starting material. This may result from the loss of stereo-
chemical integrity taking place in the extended enolate derived
from 8. Related isomerizations on isophorone derivatives bearing
either moderate or strong exocyclic acceptors have been
previously reported.34 Moreover, calculations indicate only
negligible energy differences between the (Z)- and (E)-isomers
of compounds 9 (see the Supporting Information), thus explain-
ing the observed stereochemical outcome of these reactions.
Therefore, 8 was used as the nonenriched mixture of stereoi-
somers for the synthesis of compounds 9.
The “Degradation” (Vinylene Shortening) of Merocya-
nines. Many of the above-reported syntheses of compounds 7
and 9 have met with an unexpected side reaction, namely, the
formation of a shortened merocyanine lacking a vinylene group.
To the best of our knowledge, there are only two papers
reporting this kind of reaction,28b,35 although the chain shorten-
(36) (a) Metzger, J.; Larive´, H.; Dennilauler, R.; Baralle, R.; Gaurat, C. Bull.
Soc. Chim. Fr. 1969, 1284–1293. (b) Khan, M. N.; Fleury, J.-P.; Baumlin, P.;
Hubschwerlein, C. Tetrahedron 1985, 41, 5341–5345.
(32) Moore, A. J.; Bryce, M. R. Synthesis 1991, 26–28.
(33) (a) Brooker, L. G. S. ; Heseltine, D. W. U. S. Patent 2,856,404, October
14, 1958; Chem. Abstr. 1959, 53, 3954. (b) Benniston, A. C.; Harriman, A.;
McAvoy, C. J. Chem. Soc., Faraday Trans. 1997, 93, 3653–3662.
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2001, 13, 3043–3050.
(37) The tendency of highly polarizable polyenic chromophores to be attacked
by nucleophiles has recently been acknowledged. Luo, J.; Cheng, Y.-J.; Kim,
T.-D.; Hau, S.; Jang, S.-H.; Shi, Z.; Zhou, X.-H.; Jen, A. K.-Y. Org. Lett. 2006,
8, 1387–1390.
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Tetrahedron Lett. 2001, 42, 7945–7948.
(39) (a) Nikolajewski, H. E.; Da¨hne, S.; Hirsch, B.; Jauer, E.-A. Angew.
Chem., Int. Ed. 1966, 5, 1044. (b) Eiermann, M.; Stowasser, B.; Hafner, K.;
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(35) Beverina, L.; Fu, J.; Leclercq, A.; Zojer, E.; Pacher, P.; Barlow, S.;
Van Stryland, E. W.; Hagan, D. J.; Bre´das, J.-L.; Marder, S. R. J. Am. Chem.
Soc. 2005, 127, 7282–7283.
J. Org. Chem. Vol. 73, No. 15, 2008 5893

Al´ıas et al.
TABLE 1. 3JHH and ∆J Values along the Chain
SCHEME 4
compd
3JHH(Hz)a
∆J (Hz)
7a
7b
7c
12.6
12.1, 13.4, 12.8
11.8,13.7, 11.8, 14.0, 12.5
1.0
1.8
a In CDCl3. From donor to acceptor end.
the vinylic hydrogen atom of the cyclohexene moiety is more
deshielded in the (Z)- than in the (E)-isomers, their ratio being
easily determined by integration.
3JHH coupling constants analysis along the spacer is relevant
not only at determining its stereochemistry, but also at providing
an estimation of the ground-state polarization of these mero-
cyanines, given the known correlation between 3JHH values and
C-C bond lengths.41 In fact, 3JHH values of compounds 7 (Table
1) indicate an increased (decreased) bond order for the formally
single (double) C-C bonds and, therefore, a noticeable degree
of equalization due to the contribution of the zwitterionic form
to the description of the ground-state of these compounds.
This is confirmed by ∆J values, defined as the difference
piperidinium acetate gives rise to 7b along with a small amount
of 7a. However, when ethyldiisopropylamine (DIPEA) replaced
piperidinium acetate in this reaction, the degraded product 7a
turned out to be the major one. Since DIPEA is a weak
nucleophile and cannot form iminium salts, we suggest that the
basicity, not the nucleophilicity of the used base, plays a key
role through formation of the conjugated base of the acceptor,
which is the main nucleophile carrying out the chain shortening
reactions (although both factors could be involved in the case
of piperidine). These observations can be summarized by the
mechanism of Scheme 4, where AH2 stands for a generalized
acceptor (such as 6 or 8), and which lends support to a tentative
mechanism previously proposed for malononitrile dimer.28b In
turn, this mechanism is reminiscent of the transalkenylation
reactions taking place through a Michael/retrograde Michael
sequence.11f
3
between the averaged JHH values of the formally double and
single bonds along the polymethine chain.42 Taking into account
that ∆J ≈ 6 Hz for all-trans polyenes and ∆J ≈ 0 Hz for
cyanines,43 Table 1 reveals that compounds 7 are strongly
polarized and that ground-state polarization decreases on
lengthening the spacer. (For the sake of comparison, ∆J ) 3.6
Hz for the cinnamylidene analogue of 7b.)40
Theoretical calculations on model compounds 7′, where the
methyl groups on the dithiole ring have been replaced by
hydrogen atoms, support the conclusions drawn from 1H NMR
studies on 7 and give additional information on their ground-
state properties. The molecular geometries of 7′ were optimized
at the B3P86/6-31G* level, given the good performance of this
hybrid functional at reproducing the geometry of 1,3-dithiole
derivatives.44
Thus, in the reactions of iminium salts 2, chain shortening is
observed or greatly increased in the presence of added bases,
which are needed for the weak acids, such as acceptor 8. The
degradation observed in the reaction of 2c with the stronger
acid 6 in the absence of base constitutes an exception but is in
good agreement with the susceptibility of cyanines toward
degradation, which increases with chain length.36a,39a The role
of the base is confirmed by the reactions of aldehydes 1, giving
rise to chain shortening only in the presence of piperidine.
It can be seen (Table 2) that on lengthening the π-spacer,
the increase in the SC-S bond lengths is accompanied by a
shortening of the exocyclic S2CdC bond and by an increase of
the BLA parameter (which remains close to the optimal value
maximizing ꢀ).1b These facts, together with Mulliken population
analysis, clearly show that charge transfer decreases as the length
of the conjugated spacer increases. In other words, the contribu-
tion of the zwitterionic limiting form to the description of the
ground-state of compounds 7′ is higher for the shorter derivatives.
Moreover, the electronic structure of push-pull polyenes is
quite sensitive to solvent polarity, given the stabilizing effect
of polar solvents on the zwitterionic limiting form. Thus, for
3
1H NMR and BLA Studies. As judged from JHH values,
iminium salts 2b,c have an all-trans geometry, like the
corresponding aldehydes 1b,c.20 Similarly, 1H NMR spectra of
7a-c in CDCl3 reveal an all-trans configuration of the polyenic
chain, except for the CdC bond formed in the Knoevenagel
reaction, which has (Z)-geometry as shown by the strong
deshielding experienced by the H atom located five bonds away
from the carbonyl oxygen atom.40 This assignment was con-
firmed by an X-ray diffraction study of single crystals of 7a.
Despite the poor quality of the crystals, which did not allow an
accurate structural determination, the (Z)- configuration of that
bond was unambiguously established. This geometry is also
found in the solid state of other 3-phenylisoxazol-5-ones bearing
polyenylidene substituents at C4.5a,10a
3
the vinylic hydrogen atoms of compound 7a, JHH values
increase on passing from CDCl3 (12.6 Hz) to acetone-d6 (12.9
Hz) to DMSO-d6 (13.2 Hz), indicating an increased bond order
and a more pronounced zwitterionic character in more polar
solvents. In a similar way, for compound 7b ∆J along the spacer
decreases from 1.0 Hz (in CDCl3) to 0.3 Hz (in DMSO),
(41) Radeglia, R.; Da¨hne, S. J. Mol. Struct. 1970, 5, 399–411.
(42) Marder, S. R.; Perry, J. W.; Bourhill, G.; Gorman, C. B.; Tiemann,
B. G.; Mansour, K. Science 1993, 261, 186–189.
(43) Scheibe, G.; Seiffert, W.; Hohlneicher, G.; Jutz, Ch.; Springer, H. J.
Tetrahedron Lett. 1966, 7, 5053–5059.
On the other hand, compounds 8 and 9 are present as Z/E
mixtures around the isoxazolone-exocyclic CdC bond; again,
(44) (a) Viruela, R.; Viruela, P. M.; Pou-Ame´rigo, R.; Ort´ı, E. Synth. Met.
1999, 103, 1991–1992. (b) Terkia-Derdra, N.; Andreu, R.; Salle´, M.; Levillain,
E.; Orduna, J.; Gar´ın, J.; Ort´ı, E.; Viruela, R.; Pou-Ame´rigo, R.; Sahraoui, B.;
Gorgues, A.; Favard, J.-F.; Riou, A. Chem. Eur. J. 2000, 6, 1199–1213. (c)
Andreu, R.; Gar´ın, J.; Orduna, J. Tetrahedron 2001, 57, 7883–7892.
(40) Maquestiau, A.; Van Haverbeke, Y.; Muller, R. N.; Lo Vecchio, G.;
Grassi, G. Tetrahedron Lett. 1973, 14, 4249–4251.
5894 J. Org. Chem. Vol. 73, No. 15, 2008

Iminium Salts of ω-DithiafulVenylpolyenals
TABLE 2. B3P86/6-31G* Values for C-Sa, C-C,b and C-Oc Bond Distances, BLA,d and Charges in the Dithiole (D), Spacer (π), and
Isoxazolone (A) Moieties
compd
C-S (Å)
C-C (Å)
C-O (Å)
BLA (Å)
D charge (e)
π charge (e)
A charge (e)
7′ae
7′af
7′be
7′ce
7′cf
1.756
1.740
1.760
1.762
1.749
1.370
1.386
1.367
1.365
1.378
1.211
1.220
1.210
1.210
1.221
0.044
0.015
0.049
0.051
0.022
+0.15
+0.32
+0.11
+0.09
+0.23
+0.05
+0.06
+0.09
+0.11
+0.18
-0.20
-0.38
-0.20
-0.20
-0.41
a Averaged values of the SC-S dithiole bonds. b S2CdC bond. c CdO bond d Along the polyenic spacer. e Gas phase. f In DMSO (PCM).
TABLE 3. Cyclic Voltammetric Dataa and EHOMO and ELUMO
TABLE 4. UV-vis Data
Valuesb (eV) for Compounds 7 and 9
a
a
compd
λmax (CH2Cl2) (log ꢀ)
λmax (DMSO)
compd
Eox
Ered
EHOMO
ELUMO
7a
7b
7c
9d
9a
9b
9c
547 (4.74)
520,b 553
598,b 637
646, 726b
590,b 622
624
7a
7b
7c
9d
+1.06
+0.77
+0.59
+0.85
-1.12
-6.28
-3.27
587 (4.73), 621b (4.68)
633 (4.50)
-0.93
-0.82
-1.16
-6.06
-3.39
-5.88
-3.48
582b (4.58), 609 (4.59)
606 (4.62)
614 (4.62)
-5.88c
-5.96d
-5.77c
-5.84d
-5.64c
-5.71d
-5.54c
-5.60d
-3.20c
-3.21d
-3.33c
-3.36d
-3.39c
-3.42d
-3.44c
-3.47d
626
632
9a
9b
9c
+0.59
+0.50
+0.43
-0.95
622 (4.57)
a In nm. b Shoulder.
-0.91
-0.86, -1.30
For a given length of the π-system, locking one of the CdC
bonds into the isophorone ring gives rise to more cathodic
reduction processes (cf. 7b and 9d or 7c and 9a), in good
agreement with previous comparisons on open-chain and ring-
locked merocyanines.45
a In volts, 10-3 M in CH2Cl2 vs Ag/AgCl, glassy carbon working
electrode, Pt counter electrode, 20 °C, 0.1 M Bu4NPF6, 100 mV s-1
scan rate. b B3P86/6-31G*//B3P86/6-31G* level in the gas phase,
calculated for model compounds 7′ and 9′. c Isomer with (Z)-CdC bond
exocyclic to the isoxazolone ring. d Isomer with (E)-CdC bond
exocyclic to the isoxazolone ring.
Calculations also reveal that isomers where the double bond
connecting the isophorone and isoxazolone rings is (E)- show
both lower EHOMO and ELUMO values than their (Z)-counterparts.
UV-vis Spectroscopy. The electronic absorption spectra of
compounds 7 and 9 (Table 4) show a broad, unstructured, low
energy ICT band (extending from ca. 500 to 700-800 nm),
although a shoulder is discernible in some cases. As expected,
the maxima values shift bathochromically with increasing
number of conjugated double bonds, although the vinylene shift
of compounds 9 is much less marked than that of 7. When
compounds of the same conjugation lengths are compared (7b
and 9d or 7c and 9a), it can be seen that the ring-locked
derivatives 9 show blue-shifted absorptions. In fact, the incor-
poration of the isophorone-derived fragment usually gives rise
to a hypsochromic shift,45,46 although bathochromic shifts30,47
or even both effects48 have been observed. Moreover, both series
of compounds (7 and 9) show positive solvatochromism, in good
agreement with their positive ꢀ values (see below).
Nonlinear Optical Properties. The second-order NLO
properties of compounds 7 and 9 were determined by EFISH
measurements at 1907 nm in dichloromethane. The zero-
frequency (static) values (µꢀ0) were calculated using the two-
level model, which takes dispersion into account and allows
reliable comparisons to be made, since ꢀ0 is an intrinsic value,
independent of the used wavelength (for the sake of comparison,
µꢀ0 ≈ 400 × 10-48 esu for Disperse Red 1, a common
pointing to a less alternated structure in the latter solvent. This
is confirmed through a comparison of the calculated geometries
of 7′a and 7′c in the gas phase and in DMSO (ꢀ ) 46.7,
polarized continuum model, PCM; the optimization of 7′b in
DMSO failed to converge), which reveals a strong decrease of
the BLA values on inclusion of the solvent (Table 2). Mulliken
analyses in DMSO also show that the positive charge on the
dithiole ring and the negative charge on the phenylisoxazolone
acceptor strongly increase when compared to the values of the
gas-phase structures. These facts, together with the calculated
lengthening of the CdO bond in DMSO, confirm an increase
in the zwitterionic character of these merocyanines on increasing
the polarity of the medium.
Electrochemistry. Cyclic voltammetry provides information
about the donor/acceptor interaction in D-π-A compounds,
and relevant data for merocyanines 7 and 9 are gathered in Table
3, along with calculated EHOMO and ELUMO values.
All compounds (except for 9c) show two irreversible waves,
corresponding to the oxidation of the dithiafulvene donor and
the reduction of the isoxazolone fragment, respectively. In
compounds 7, an increase in the length of the π-spacer gives
rise to both easier oxidation and reduction processes, indicating
a progressively weaker interaction between the D and A moieties
because of the less effective electron donation (withdrawal) felt
by the acceptor (donor) on passing from 7a to 7c. These
observations also point to a smaller contribution of the zwitte-
rionic limiting form to the ground-state for the longer deriva-
tives, in good agreement with the results of theoretical calcu-
(45) Staub, K.; Levina, G. A.; Barlow, S.; Kowalczyk, T. C.; Lackritz, H.;
Barzoukas, M.; Fort, A.; Marder, S. R. J. Mater. Chem. 2003, 13, 825–833.
(46) (a) Shu, C.-F.; Shu, Y.-C.; Gong, Z.-H.; Peng, S. M.; Lee, G.-H.; Jen,
A. K. Y. Chem. Mater. 1998, 10, 3284–3286. (b) Zhang, C.; Ren, A. S.; Wang,
F.; Zhu, J.; Dalton, L. R.; Woodford, J. N.; Wang, C. H. Chem. Mater. 1999,
11, 1966–1968.
lations. The increase (decrease) of the calculated EHOMO (ELUMO
values on lengthening the polyenic spacer nicely parallels the
observed cyclovoltammetric behavior.
)
(47) Hsu, C.-C.; Shu, C.-F.; Huang, T.-H.; Wang, C. H.; Lin, J.-L.; Wang,
Y.-K.; Zang, Y.-L. Chem. Phys. Lett. 1997, 274, 466–472.
(48) (a) Shu, C.-F.; Tsai, W.-J.; Jen, A. K.-Y. Tetrahedron Lett. 1996, 37,
7055–7058. (b) Shu, Y.-C.; Gong, Z.-H.; Shu, C.-F.; Breitung, E. M.; McMahon,
R. J.; Lee, G.-H.; Jen, A. K.-Y. Chem. Mater. 1999, 11, 1628–1632.
Compounds 9 show exactly the same trends as those displayed
by their acyclic analogues 7.
J. Org. Chem. Vol. 73, No. 15, 2008 5895

Al´ıas et al.
TABLE 5. Experimentala and Calculatedb, c NLO Properties
experimental
TD-DFTd
E (eV)
CPHFe
f
f
g
f
compd
µꢀ
µꢀ0
µg (D)
µe (D)
f
µg (D)
ꢀtot
µꢀ0
7a
7b
7c
250
1100
2193
719
153
565
1091
382
9.55
10.90
12.16
10.69
11.94
11.35
12.84
12.24
14.00
13.09
15.04
10.90
16.98
23.11
15.85
18.24
23.27
25.90
28.74
31.63
34.24
37.33
3.05
2.80
2.57
2.77
2.82
2.51
2.55
2.34
2.36
2.18
2.20
0.6025
1.0964
1.5193
1.0013
0.9446
1.3197
1.2398
1.6672
1.5823
1.9650
1.8810
10.06
10.94
11.71
11.01
12.26
11.32
12.79
11.78
13.50
12.20
14.09
15
54
116
44
23
94
74
387
983
213
272
577
794
1163
1652
1944
2827
9dh
9di
9ah
9ai
9bh
9bi
9ch
9ci
2750
4252
5539
1475
2229
2843
63
165
124
251
203
a In CH2Cl2, at 1907 nm. b On B3P86/6-31G* geometries. c Calculations carried out on compounds 7′ and 9′ instead of 7 and 9, respectively.
f
g
d B3P86/6-31G* level. e CPHF/6-31G* level. In 10-48 esu. Experimental accuracy ( 10%. In 10-30 esu. h Calculated values for the isomer with
(Z)-CdC bond exocyclic to the isoxazolone ring. i Calculated values for the isomer with (E)-CdC bond exocyclic to the isoxazolone ring.
benchmark in organic NLO-phores).49 Inspection of Table 5
reveals the expected increase in µꢀ0 on lengthening the
conjugation path for series 7 and 9, giving rise to high µꢀ0 values
for the longer derivatives.
to acceptor charge transfer, which goes down roughly as 1/L,
reflecting the increasing difficulty of separating charges over
larger distances.52 This agrees with the previously discussed
decrease in the zwitterionic character of the ground-state for
the longer derivatives.
Calculated molecular hyperpolarizabilities on model com-
pounds 7′ and 9′ using the coupled perturbed Hartree-Fock
(CPHF) method show the same trend, although theoretical µꢀ0
values are systematically underestimated, probably due to the
fact that solvent effects were not considered in the calculations.
For compounds 9, present as (Z)/(E) mixtures around the
isoxazolone-exocyclic bond, calculations also show that the
(E)-isomers have higher µꢀ0 values (by ca. 40%) than the (Z)-
isomers, a fact which is due to the interplay of several factors:
the (E)-isomers have higher dipole moments and lower total
hyperpolarizabilities (ꢀtot), but the angle formed by the ground-
state dipole moment and the vectorial hyperpolarizability is
much smaller for the (E)- than for the (Z)-isomer, resulting in
higher µꢀ0 values for the former. Although calculations on both
configurations lead to analogous qualitative conclusions, it is
not surprising that the calculated values for the more polar (E)-
isomers are closer to the experimental ones, provided that these
isomers must be favored at the high electric fields employed
during the EFISH measurements.
The effect of ring-locking on the NLO (and thermal)
properties of these compounds is not clear: when molecules of
the same conjugation length are compared it can be seen that
the introduction of the isophorone-derived spacer gives rise to
either a decrease (cf. 7b and 9d) or an increase (cf. 7c and 9a)
in µꢀ0. This structural modification usually results in diminished
ꢀ (or µꢀ) values11d,30,46b,48b and a variety of reasons, such as
distortions from planarity and poor alignment of the µ and ꢀ
vectors, have been invoked to account for this behavior. On
the other hand, only a weak effect on the µꢀ0 values upon ring-
locking has been reported in other instances.45 In a similar way,
the incorporation of cyclohexene fragments into the spacer has
been reported to afford merocyanines with enhanced thermal
stabilities,46,48 but this is not the case with the compounds herein
reported. Their thermal stabilities were studied using thermo-
gravimetric analysis (TGA) and their decomposition tempera-
tures (Td) were estimated as the temperature that is the intercept
of the leading edge of the weight loss by the baseline of the
TGA scans. When compared to 7b (Td ) 156 °C), its ring-
locked analogue 9d showed a decreased thermal stability (Td
) 128 °C), and only a negligible increase in stability on ring-
locking was observed for compounds 7c (Td ) 105 °C) and 9a
(Td ) 111 °C).
To get a more intuitive description of the NLO properties of
7 and 9, we have also carried out TD-DFT calculations which,
despite their limited description of charge transfer transitions,50
allow the determination of the parameters involved in the two-
level model (ꢀ0
∆µge f/E3, where ∆µge is the difference
Finally, it is pertinent to compare the NLO responses of
the compounds herein described to those of related derivatives.
The donor ability of the dithiafulvene moiety, as judged
from the µꢀ0 values of previously reported isoxazolone-
containing merocyanines of the same conjugation length, is
similar to that of trimethyl-2-methyleneindoline (Fischer’s
base)2b and N,N-dimethylaniline5a (up to ca. 10 conjugated
carbon atoms) and superior to that of tetrathiafulvalene.53
Comparison with other proaromatic donors is difficult since only
between the excited and ground-state dipole moments, µe and
µg respectively, f is the oscillator strength, and E is the first
excitation energy).51 Within each series of compounds (7 and
9), ∆µge and f increase, and E decreases on increasing the
conjugation path, qualitatively explaining the higher µꢀ0 values
for the longer derivatives. Table 5 also shows that ∆µge values
are positive, in agreement with the observed positive solvato-
chromism, and that on lengthening the chain there is a much
steeper increase in µe than in µg values. The smooth increase
of the latter is a consequence of two opposing trends, namely,
the increase in molecular length (L) and the decrease of donor
(52) (a) Dulcic, A.; Flytzanis, C.; Tang, C. L.; Pe´pin, D.; Fe´tizon, M.;
Hoppilliard, Y. J. Chem. Phys. 1981, 74, 1559–1563. (b) Blanchard-Desce, M.;
Alain, V.; Midrier, L.; Wortmann, R.; Lebus, S.; Glania, C.; Kra¨mer, P.; Fort,
A.; Muller, J.; Barzoukas, M. J. Photochem. Photobiol. A 1997, 105, 115–121.
(c) Alain, V.; Re´doglia, S.; Blanchard-Desce, M.; Lebus, S.; Lukaszuk, K.;
Wortmann, R.; Gubler, U.; Bosshard, C.; Gu¨nter, P. Chem. Phys. 1999, 245,
51–71.
(49) Singer, K. D.; Sohn, J. E.; King, L. A.; Gordon, H. M.; Katz, H. E.;
Dirk, C. W. J. Opt. Soc. Am. B 1989, 6, 1339–1350.
(50) (a) Dreuw, A.; Head-Gordon, M. J. Am. Chem. Soc. 2004, 126, 4007–
4016, but see. (b) Guillaume, M.; Champagne, B.; Zutterman, F. J. Phys. Chem.
A 2006, 110, 13007–13013.
(53) Gonza´lez, M.; Segura, J. L.; Seoane, C.; Mart´ın, N.; Gar´ın, J.; Orduna,
J.; Alcala´, R.; Villacampa, B.; Herna´ndez, V.; Lo´pez Navarrete, J. T. J. Org.
Chem. 2001, 66, 8872–8882.
(51) Kanis, D. R.; Ratner, M. A.; Marks, T. J. Chem. ReV. 1994, 94, 195–
242.
5896 J. Org. Chem. Vol. 73, No. 15, 2008

Iminium Salts of ω-DithiafulVenylpolyenals
to cool to room temperature. The solution was added to ice-cooled
Et2O (75 mL), and the resulting dark blue precipitate was isolated
by filtration, washed with cool Et2O, and dried. Hydrolysis of this
crude iminium salt 2c and subsequent purification of the final
product (1c) was carried out exactly as described above for the
preparation of 1b. Yield from 3: 104 mg, 55%. The product was
identical in all respects to an authentic sample prepared as
previously reported.20
two compounds, structurally analogous to 7a, featuring a
benzothiazolylidene and a 4-pyridylidene group, respectively,
have been described10a and their µꢀ0 valuessdetermined by
Hyper-Rayleigh Scattering (HRS)sare presumed to be resonance-
enhanced. In any case, the negative µꢀ0 value measured for the
pyridylidene derivative points to this donor as the strongest one in
these series. Focusing on the acceptor fragment, when µꢀ0 values
of dithiafulvene-based NLO-phores bearing different acceptors are
compared, it can be seen that 3-phenyl-5-isoxazolone is a more
efficient electron-withdrawing group than most previously used
ones,11d,e,28b being only surpassed by 1,1,3-tricyano-2-
phenylpropene.11f
In summary, the hitherto unreported N,N-dimethyliminium
salts formally derived from ω-(2,3-dimethyl-1,4-dithiafulve-
nyl)polyenals have been easily prepared from trimethyl-1,3-
dithiolium tetrafluoroborate. These iminium salts can be smoothly
hydrolyzed to the corresponding aldehydes, in what constitutes
the shortest, highest-yielding route to these important polyenals
so far reported. Moreover, the reactivity of both kinds of
electrophiles in Knoevenagel-type reactions has been studied
using isoxazolone-containing proaromatic acceptors, and imi-
nium salts show a higher reactivity, especially toward weaker
acids. In these reactions, a “degraded” merocyanine, lacking a
vinylene group, is usually formed along with the expected one,
and a mechanistic rationale to account for this fact is offered.
1H NMR, electrochemical and theoretical studies reveal that the
push-pull dithiafulvenes herein reported are strongly polarized
and that the contribution of the zwitterionic form to the ground-
state decreases on lengthening the π-spacer. These compounds
featuring two proaromatic end groups have close to optimal BLA
values and display high molecular hyperpolarizabilities.
(E,E)-N,N-Dimethyl 6-(4,5-dimethyl-1,3-dithiol-2-yliden)hexa-
2,4-dienylideniminium Tetrafluoroborate (2c). To a solution of
aldehyde 1c (265 mg, 1.18 mmol) in absolute ethanol (30 mL) was
added dimethylammonium tetrafluoroborate (157 mg, 1.18 mmol).
The mixture was refluxed for 7 h and cooled and the solvent
distilled. Et2O (100 mL) was added, and the resulting precipitate
was filtered off, washed with Et2O, and dried. Yield: dark blue
solid (370 mg, 92%). Mp: 110-112 °C. IR (KBr, cm-1): 1653
1
(CdN). H NMR (CD2Cl2, 400 MHz): δ 7.92 (d, J ) 11.3 Hz,
1H), 7.53 (t, J ) 12.8 Hz, 1H), 7.10 (t, J ) 12.8 Hz, 1H), 6.40 (d,
J ) 12.3 Hz, 1H), 6.30 (t, J ) 12.8 Hz, 1H), 6.17 (dd, J ) 13.4
Hz, J′ ) 11.3 Hz, 1H), 3.48 (s, 3H), 3.27 (s, 3H), 2.11 (s, 6H). 13
C
NMR (CD2Cl2, 75 MHz): δ 165.7, 162.8, 161.9, 147.7, 128.4,
128.2, 123.5, 112.4, 111.9, 48.2, 40.0, 14.0, 13.6. MS (ESI+): m/z
252 (C13H18NS2)+. Anal. Calcd for C13H18BF4NS2: C, 46.03; H,
5.35; N, 4.13. Found: C, 45.64; H, 5.08; N, 4.49.
Compounds 7a,b from 1a,b: General Procedure. 3-Phenyl-5-
isoxazolone (6, 94 mg, 0.58 mmol) was added to a solution of 0.58
mmol of the corresponding aldehyde (1a,b) in absolute ethanol (10
mL). The solution was refluxed under argon with exclusion of light
for 1.5-2 h (TLC monitoring) and then allowed to cool to room
temperature. The resulting solid was filtered off, washed with cold
ethanol, and dried.
(Z)-4-[2-(4,5-Dimethyl-1,3-dithiol-2-ylidene)ethylidene]-3-phenyl-
5-isoxazolone (7a). Yield: purple solid (143 mg, 78%). Evaporation
of the filtrate and column chromatography (silica gel) using CH2Cl2/
Et2O (9:1) as eluent gave a second fraction (30 mg, 16%). Mp:
Experimental Section
Compounds 1a,22 2a,15 3,15 5,16 and 1032 were prepared as
previously described.
1
238-239 °C. IR (Nujol, cm-1): 1745 (CdO). H NMR (CDCl3,
300 MHz): δ 7.79 (d, J ) 12.6 Hz, 1H), 7.59-7.49 (m, 5H), 7.32
(d, J ) 12.6 Hz, 1H), 2.13 (s, 6H). 13C NMR (CDCl3, 100 MHz):
δ 171.9, 170.9, 162.4, 140.6, 130.2, 129.0, 128.8, 128.5, 128.3,
128.1, 108.6, 103.9, 13.7, 13.6. MS (EI+): m/z 315 (M+·, 100),
159 (30), 114 (45). HRMS (EI+): calcd for C16H13NO2S2 315.0388,
found 315.0399. Anal. Calcd for C16H13NO2S2: C, 60.93; H, 4.15;
N, 4.44. Found: C, 61.23; H, 4.22; N, 4.63.
(E)-N,N-Dimethyl 4-(4,5-Dimethyl-1,3-dithiol-2-yliden)but-2-
enylideniminium Tetrafluoroborate (2b). To a solution of trimethyl-
1,3-dithiolium tetrafluoroborate (3) (734 mg, 3.15 mmol) in Ac2O
(6 mL) 3-dimethylaminoacrolein (929 mg, 9.37 mmol) was added.
The mixture was stirred under argon at room temperature for 30
min. The resulting solution was added to ice-cooled Et2O (125 mL),
and the resulting solid was filtered off, washed with cold Et2O,
and dried. Yield: maroon solid (930 mg, 94%). Mp: 207-208 °C.
(Z)-4-[(E)-4-(4,5-Dimethyl-1,3-dithiol-2-ylidene)but-2-enylidene]-
3-phenyl-5-isoxazolone (7b). Yield: dark blue solid (146 mg, 74%).
Mp: 203-204 °C. IR (Nujol, cm-1): 1746 (CdO). 1H NMR
(CDCl3, 400 MHz): δ 7.63-7.45 (m, 6H), 7.29 (d, J ) 12.7 Hz,
1H), 6.94 (t, J ) 12.8 Hz, 1H) 6.44 (d, J ) 11.9 Hz, 1H), 2.07 (s,
3H), 2.09 (s, 3H). 13C NMR (CDCl3, 100 MHz): δ 170.1, 161.5,
158.4, 148.2, 146.7, 129.3, 128.0, 127.7, 127.2, 125.7, 125.4, 119.7,
110.8, 108.3, 12.7, 12.3. HRMS (ESI+): calcd for C18H16NO2S2
(M + H) 342.0617, found 342.0627. Anal. Calcd for C18H15NO2S2:
C, 63.32; H, 4.43; N, 4.10. Found: C, 63.57; H, 4.70; N, 4.38.
Synthesis of 7a from 2a. To a solution of iminium salt 2a (53
mg, 0.18 mmol) in anhydrous DMF (2 mL) were added 3-phenyl-
5-isoxazolone (6) (32 mg, 0.198 mmol) and piperidinium acetate
(29 mg, 0.198 mmol). The mixture was stirred under argon at room
temperature for 1 h. AcOEt (30 mL) was then added, and the
resulting organic layer was washed with water (3 × 30 mL), dried
(MgSO4), and evaporated. The residue was purified by flash
chromatography (silica gel) using CH2Cl2/Et2O (9:1). Yield: 53 mg,
91%.
1
IR (Nujol, cm-1): 1635 (CdN). H NMR (DMSO-d6, 400 MHz):
δ 8.27 (d, J ) 11.1 Hz, 1H), 7.53 (t, J ) 12.8 Hz, 1H), 6.76 (d, J
) 12.4 Hz, 1H), 6.26 (dd, J ) 13.0 Hz, J′ ) 11.1 Hz), 3.41 (s,
3H), 3.27 (s, 3H), 2.17 (s, 3H), 2.15 (s, 3H). 13C NMR (DMSO-d6,
100 MHz): δ 165.8, 165.6, 151.9, 127.7, 127.6, 110.3, 110.2, 47.2,
39.2, 13.2, 12.9. MS (MALDI+): m/z 226 (C11H16NS2)+. Anal.
Calcd for C11H16BF4NS2: C, 42.19; H, 5.15; N, 4.47. Found: C,
41.81; H, 4.82; N, 4.79.
(E)-4-(4,5-Dimethyl-1,3-dithiol-2-yliden)but-2-enal (1b). To a
solution of 2b (313 mg, 1.0 mmol) in CH2Cl2 (20 mL) was added
aqueous NaOH (5 N, 15 mL). The mixture was stirred at room
temperature for 20-30 min (TLC monitoring), and the organic layer
was separated, washed with saturated aqueous NaCl (20 mL) and
water (20 mL), and dried (MgSO4). The crude product was purified
by flash chromatography on silica gel using hexane/AcOEt (9:1).
Yield: 156 mg, 79%. The product was identical in all respects to
an authentic sample prepared as previously reported.20
Synthesis of 7b from 2b. To a solution of iminium salt 2b (44
mg, 0.14 mmol) in anhydrous DMF (2 mL) was added 3-phenyl-
5-isoxazolone (6) (24 mg, 0.15 mmol). The mixture was stirred
under argon for 7 h. AcOEt (30 mL) was then added, and the
resultant organic layer was washed with water (3 × 30 mL), dried
(E,E)-6-(4,5-Dimethyl-1,3-dithiol-2-yliden)hexa-2,4-dienal (1c).
To a solution of salt 3 (197 mg, 0.85 mmol) in Ac2O (3 mL) was
added dropwise a solution of (E,E)-5-(dimethylamino)penta-2,4-
dienal (5, 106 mg, 0.85 mmol) in anhydrous CH2Cl2 (3 mL). The
mixture was heated under argon at 70 °C for 3 h and then allowed
J. Org. Chem. Vol. 73, No. 15, 2008 5897

Al´ıas et al.
(MgSO4), and evaporated. The residue was purified by flash
chromatography (silica gel) using hexane/AcOEt (8:2). Yield: 30
mg, 62%.
cm-1): 1724 (CdO). 1H NMR (CDCl3, 300 MHz, -20 °C): δ 8.05
(s, 1H, (Z)-isomer), 7.56-7.36 (m, 10H), 6.67 (dd, J ) 14.4 Hz, J′
) 11.8 Hz, 1H), 6.56 (dd, J ) 14.4 Hz, J′ ) 11.8 Hz, 1H), 6.30
(d, J ) 14.4 Hz, 1H), 6.22 (d, J ) 11.8 Hz, 1H), 6.20 (s, 1H,
(E)-isomer), 6.09 (d, J ) 11.8 Hz, 1H), 5.54 (d, J ) 14.4 Hz, 1H),
3.08 (s, 2H, (E)-isomer), 2.27 (s, 4H), 2.01 (s, 6H), 1.99 (s, 3H),
1.98 (s, 3H), 1.22 (s, 2H, (E)-isomer), 1.03 (s, 6H, (E)-isomer),
0.77 (s, 6H, (Z)-isomer). 13C NMR spectrum was not registered
due to its low solubility. MS (MALDI+): m/z 436 (M + H). Anal.
Calcd for C25H25NO2S2: C, 68.93; H, 5.78; N, 3.22. Found: C,
68.67; H, 5.92; N, 3.51.
(Z)-4-[(2E,4E)-6-(4,5-Dimethyl-1,3-dithiol-2-ylidene)hexa-2,4-di-
enylidene]-3-phenyl-5-isoxazolone (7c). To a solution of iminium
salt 2c (112 mg, 0.33 mmol) in anhydrous DMF (7 mL) was added
3-phenyl-5-isoxazolone (6, 55 mg, 0.34 mmol). The mixture was
stirred under argon at 0 °C for 2 h. AcOEt (60 mL) was added,
and the resultant organic layer was washed with water (3 × 50
mL), dried over MgSO4, and evaporated. The residue was purified
by flash chromatography (silica gel) using hexane/AcOEt (8:2).
Yield: dark blue solid (30 mg, 25%). Mp: 119-120 °C. IR (Nujol,
cm-1): 1748 (CdO). 1H NMR (CDCl3, 400 MHz): δ 7.75 (dd, J )
13.7 Hz, J′ ) 12.4 Hz, 1H), 7.62-7.45 (m, 5H), 7.30 (d, J ) 12.4
Hz, 1H), 7.01 (dd, J ) 13.7 Hz, J′ ) 11.8 Hz, 1H), 6.63 (dd, J )
13.7 Hz, J′ ) 11.8 Hz, 1H), 6.31 (dd, J ) 13.7 Hz, J′ ) 11.8 Hz,
1H), 6.25 (d, J ) 11.8 Hz, 1H), 2.04 (s, 3H), 2.02 (s, 3H). 13C
NMR (CDCl3, 75 MHz): δ 170.5, 162.4, 154.1, 151.2, 149.1, 140.7,
130.4, 129.0, 128.3, 128.1, 125.9, 124.6, 124.6, 124.5, 111.7, 111.1,
13.6, 13.2; HRMS (ESI+): calcd for C20H18NO2S2 (M + H)
368.0773, found 368.0765. Anal. Calcd for C20H17NO2S2: C, 65.37;
H, 4.66; N, 3.81. Found: C, 65.04; H, 4.79; N, 4.10.
4-{3-(1E,3E)-[ 5-(4,5-Dimethyl-1,3-dithiol-2-ylidene)penta-1,3-
dienyl]-5,5-dimethyl-2-cyclohexen-1-ylidene}-3-phenyl-5-isoxazolo-
ne (9b). To a solution of iminium salt 2b (227 mg, 0.725 mmol) in
anhydrous DMF (8 mL) were added compound 8 (204 mg, 0.725
mmol) and piperidinium acetate (105 mg, 0.725 mmol). The mixture
was stirred under argon at 0 °C for 4.5 h. AcOEt (80 mL) was
added, and the organic layer was washed with water (3 × 80 mL),
dried (MgSO4), and evaporated. The residue was purified by flash
chromatography (silica gel) using hexane/AcOEt (8/2). Yield: dark
blue solid (57 mg, 17%). Mp: 198-201 °C. IR (Nujol, cm-1): 1731
1
(CdO). H NMR (CDCl3, 400 MHz): δ 8.11 (s, 1H, (Z)-isomer),
4-(3,5,5-Trimethyl-2-cyclohexen-1-ylidene)-3-phenyl-5-isoxazolo-
ne (8). Compound 8 was prepared as previously reported29 and
obtained as a Z/E mixture (10:3 ratio). Mp: 161-163 °C. Recrys-
tallization from methanol afforded the (Z)- isomer nearly free from
the (E)-isomer (10:1 ratio). Mp: 168-169 °C (lit.29 mp 168-170
°C). IR (Nujol, cm-1): 1728 (CdO). 1H NMR (CDCl3, 300 MHz):
δ (Z)-isomer: 7.96 (s, 1H), 7.54-7.38 (m, 5H), 2.09 (s, 2H), 2.04
(s, 3H), 1.99 (s, 2H), 0.76 (s, 6H); δ (E)-isomer: 7.54-7.38 (m,
5H), 6.12 (s, 1H), 3.06 (s, 2H), 1.68 (s, 3H), 1.25 (s, 2H), 1.02 (s,
6H). 13C NMR (CDCl3, 100 MHz): δ 164.5, 163.6, 162.9, 161.7,
161.4, 159.8, 131.0, 130.8, 130.1, 130.0, 128.7, 128.6, 121.9, 121.0,
111.1, 110.8, 45.8, 45.5, 41.9, 38.9, 32.4, 32.0, 28.2, 27.8, 25.9,
25.7. MS (EI+) m/z 281 (M+·, 21), 266 (100), 248 (70), 220 (31),
117 (22), 105 (21), 91 (21), 77 (33).
4-[3-(4,5-Dimethyl-1,3-dithiol-2-ylidenemethyl)-5,5-dimethyl-2-
cyclohexen-1-ylidene]-3-phenyl-5-isoxazolone (9d). To a solution
of 4,5-dimethyl-2-methylthio-1,3-dithiolium tetrafluoroborate (10)
(264 mg, 1 mmol) in pyridine (5 mL) were added compound 8
(mixture of isomers) (281 mg, 1 mmol) and triethylamine (0.4 mL).
The mixture was refluxed with exclusion of light for 30 min and
cooled, and the solvents were distilled. The crude product was
dissolved in CH2Cl2 and washed with HCl 1 N (3 × 100 mL) and
water (2 × 100 mL). The organic layer was dried (MgSO4),
evaporated, and purified by chromatography (silica gel) using
CH2Cl2/Et2O (9:1) as eluent. Yield: dark blue solid (143 mg, 35%).
Mp: 191-195 °C. IR (Nujol, cm-1): 1701 (CdO). 1H NMR
(CDCl3, 300 MHz) δ: 7.86 (s, 1H, (Z)-isomer), 7.49-7.40 (m, 10H),
6.34 (s, 1H), 6.29 (s, 1H), 5.89 (s, 1H, (E)-isomer), 3.08 (s, 2H,
(E)-isomer), 2.26 (s, 2H, (Z)-isomer), 2.15 (s, 2H, (Z)-isomer), 2.05
(s, 3H), 2.00 (s, 3H), 1.99 (s, 3H), 1.98 (s, 3H), 1.30 (s, 2H, (E)-
isomer), 1.03 (s, 6H, (E)-isomer), 0.77 (s, 6H, (Z)-isomer). 13C NMR
spectrum was not registered due to its low solubility. MS (EI+):
m/z 409 (M+·, 100), 394 (38), 131 (36), 105 (20), 84 (47), 59 (21).
Anal. Calcd for C23H23NO2S2: C, 67.45; H, 5.66; N, 3.42. Found:
C, 67.68; H, 5.54; N, 3.70.
7.57-7.39 (m, 10H), 6.82 (dd, J ) 15.0 Hz, J′ ) 11.2 Hz, 1H),
6.66 (dd, J ) 15.0 Hz, J′ ) 11.3 Hz, 1H), 6.52 (d, J ) 15.0 Hz,
1H), 6.40 (dd, J ) 14.3 Hz, J′ ) 11.5 Hz, 1H), 6.33 (dd, J ) 14.3
Hz, J′ ) 11.7 Hz, 1H), 6.28 (s, 1H, (E)-isomer), 6.16 (d, J ) 11.5
Hz, 1H), 6.15 (dd, J ) 14.3 Hz, J′ ) 11.2 Hz, 1H), 6.08 (d, J )
11.7 Hz, 1H), 5.98 (dd, J ) 14.2 Hz, J′ ) 11.3 Hz, 1H), 5.76 (d,
J ) 15.0 Hz, 1H), 3.10 (s, 2H, (E)-isomer), 2.28 (s, 2H, (Z)-isomer),
2.01 (s, 2H, (Z)-isomer), 1.98 (s, 6H), 1.95 (s, 6H), 1.25 (s, 2H,
(E)-isomer), 1.04 (s, 6H, (E)-isomer), 0.79 (s, 6H, (Z)-isomer). 13
C
NMR spectrum was not registered due to its low solubility. HRMS
(ESI+): calcd for C27H28NO2S2 (M + H) 462.1556, found 462.1547.
Anal. Calcd for C27H27NO2S2: C, 70.25; H, 5.90; N, 3.03. Found:
C, 70.01; H, 6.22; N, 3.38.
4-{3-(1E,3E,5E)-[7-(4,5-Dimethyl-1,3-dithiol-2-ylidene)hepta-
1,3,5-trienyl]-5,5-dimethyl-2-cyclohexen-1-ylidene}-3-phenyl-5-iso-
xazolone (9c). To a solution of iminium salt 2c (137 mg, 0.4 mmol)
in anhydrous DMF (5 mL) was added compound 8 (123 mg, 0.44
mmol) and piperidinium acetate (64 mg, 0.44 mmol). The mixture
was stirred under argon at 0 °C for 3 h. AcOEt (60 mL) was added,
and the organic layer was washed with water (3 × 50 mL), dried
(MgSO4), and evaporated. The residue was purified by flash
chromatography (silica gel) using hexane/AcOEt (9:1). Yield: dark
blue-green solid (41 mg, 21%). Mp: 194-195 °C. IR (KBr, cm-1):
1
1722 (CdO). H NMR (CDCl3, 300 MHz): δ 8.13 (s, 1H, (Z)-
isomer), 7.57-7.39 (m, 10H), 6.78 (dd, J ) 14.9 Hz, J′ ) 10.9
Hz, 1H), 6.65 (dd, J ) 14.9 Hz, J′ ) 11.3 Hz, 1H), 6.59-6.41 (m,
3H), 6.40-5.95 (m, 9H), 5.79 (d, J ) 15.0 Hz, 1H), 3.10 (s, 2H,
(E)-isomer), 2.29 (s, 4H), 1.97 (s, 6H), 1.94 (s, 6H), 1.31 (s, 2H,
(E)-isomer), 1.05 (s, 6H, (E)-isomer), 0.80 (s, 6H, (Z)-isomer). 13
C
NMR spectrum was not registered due to its low solubility. HRMS
(ESI+): calcd for C29H30NO2S2 (M + H) 488.1712, found 488.1716.
Anal. Calcd for C29H29NO2S2: C, 71.42; H, 5.99; N, 2.87. Found:
C, 71.20; H, 6.28; N, 3.09.
Acknowledgment. Financial support from MEC-FEDER
(CTQ2005-01368 and MAT2005-06373-C02) and Gobierno de
Arago´n-Fondo Social Europeo (E39) is gratefully acknowledged.
4-{3(E)-[(4,5-Dimethyl-1,3-dithiol-2-ylidene)prop-1-enyl]-5,5-di-
methyl-2-cyclohexen-1-ylidene}-3-phenyl-5-isoxazolone (9a). To a
solution of iminium salt 2a (120 mg, 0.418 mmol) in anhydrous
DMF (4 mL) were added compound 8 (129 mg, 0.45 mmol) and
piperidinium acetate (65 mg, 0.45 mmol). The mixture was stirred
under argon at room temperature for 2 h. AcOEt (50 mL) was
added, and the organic layer was washed with water (3 × 50 mL),
dried (MgSO4), and evaporated. The residue was purified by flash
chromatography (silica gel) using hexane/AcOEt (9:1, then 7:3).
Yield: dark blue solid (83 mg, 45%). Mp: 169-170 °C. IR (Nujol,
Supporting Information Available: General experimental
methods, NMR spectra of new compounds, computed energies,
and Cartesian coordinates of optimized geometries. This material
is available free of charge via the Internet at http://pubs.acs.org.
JO800801Q
5898 J. Org. Chem. Vol. 73, No. 15, 2008