Pyridoneimines and pyridonemethides: Substituent- and solvent-tunable intramolecular charge transfer and geometric isomerism

Article abstract of DOI:10.1021/jo015937c

We have prepared and fully characterized by means of multinuclear NMR and UV-vis spectroscopy a series of pyridoneimines and pyridonemethides in order to show how it is possible to finely tune φ-electron structure properties by properly exploiting substituent and solvent effects. Substituents with different electron-withdrawing capacities were introduced in pyridoneimines 2-4, pyridonemethides 5 and 6, and pyridine sulfonamido derivatives 7-9. The anisochrony of the carbon position of the azinium ring (geometric isomerism) and the exploitation of previously reported ¹³C and ¹⁵N shift/φ-electron density relationships allowed the investigation of the extent of intramolecular charge transfer from the donor group to the acceptor pyridinium moiety. By combining different substitutions with the polarity of the surrounding media, we were able to access a whole range of push-pull electron structures in solution, from fully aromatic-zwitterionic to quinoidneutral, through many possible intermediate situations along the path. Due to the strict correlation between the φ-electron structure of push-pull derivatives and many photonic properties such as nonlinear optical activity, we believe that the achieved results should be valuable for the development of new efficient, tailor-made, heteroaromatic systems with optimized features as advanced organic materials.

Full text of DOI:10.1021/jo015937c

J . Org. Chem. 2001, 66, 8883-8892
8883
P yr id on eim in es a n d P yr id on em eth id es: Su bstitu en t- a n d
Solven t-Tu n a ble In tr a m olecu la r Ch a r ge Tr a n sfer a n d Geom etr ic
Isom er ism
Alessandro Abbotto, Silvia Bradamante, and Giorgio A. Pagani*
Dipartimento di Scienza dei Materiali, Universita` di Milano-Bicocca, Via Cozzi 53,
I-20125, Milano, Italy, and Centro CNR Speciali Sistemi Organici, Via Golgi 19, I-20133, Milano, Italy
giorgio.pagani@mater.unimib.it
Received J uly 17, 2001
We have prepared and fully characterized by means of multinuclear NMR and UV-vis spectroscopy
a series of pyridoneimines and pyridonemethides in order to show how it is possible to finely tune
π-electron structure properties by properly exploiting substituent and solvent effects. Substituents
with different electron-withdrawing capacities were introduced in pyridoneimines 2-4, pyridone-
methides 5 and 6, and pyridine sulfonamido derivatives 7-9. The anisochrony of the carbon
position of the azinium ring (geometric isomerism) and the exploitation of previously reported 13C
and 15N shift/π-electron density relationships allowed the investigation of the extent of intra-
molecular charge transfer from the donor group to the acceptor pyridinium moiety. By combining
different substitutions with the polarity of the surrounding media, we were able to access a whole
range of push-pull electron structures in solution, from fully aromatic-zwitterionic to quinoid-
neutral, through many possible intermediate situations along the path. Due to the strict correlation
between the π-electron structure of push-pull derivatives and many photonic properties such
as nonlinear optical activity, we believe that the achieved results should be valuable for the
development of new efficient, tailor-made, heteroaromatic systems with optimized features as
advanced organic materials.
In tr od u ction
nonlinear second-order polarizability â with a geometrical
parameter, the bond-length alternation (BLA), defined
as the average difference between the length of adjacent
carbon-carbon formal single and double bonds in the
polyconjugated molecule.3 It has been shown that opti-
mization of â requires a specific combination of geometric
and electronic parameters, strictly dictated by the nature
and position of terminal groups as well as surrounding
media properties,4,5 which leads to an optimal electronic
pattern of the ground state of the chromophore.
Investigation of the properties of push-pull deriva-
tives, where a conjugated π-system is end-capped by a
donor and an acceptor group, has been the focus of many
recent works, including the design of new efficient organic
materials.1 Such systems can be approximately described
in terms of the contribution of two limit forms, with an
intramolecular charge-transfer taking place from the
donor to the acceptor moiety. The importance and relative
stability of the two resonance forms define the π-electron
structure and, ultimately, many properties of the push-
pull molecules. In the past several years, a number of
studies have focused the attention on the relationship
between the electronic nature of the constituting parts
of the push-pull molecule and the value of nonlinear
optical figures of merit.2 Within this research field,
Marder and co-workers have correlated the value of the
We here report an investigation on a class of pyridine-
based push-pull derivatives, having the general formula
(3) (a) Marder, S. R.; Beratan, D. N.; Cheng, L. T. Science 1991,
252, 103-106. (b) Marder, S. R.; Cheng, L. T.; Tiemann, B. G.; Friedli,
A. C.; Blancharddesce, M.; Perry, J . W.; Skindhoj, J . Science 1994, 263,
511-514. (c) Wong, K. Y.; J en, A. K. Y.; Rao, V. P.; Drost, K. J . J .
Chem. Phys. 1994, 100, 6818-6825. (d) Blancharddesce, M.; Alain, V.;
Bedworth, P. V.; Marder, S. R.; Fort, A.; Runser, C.; Barzoukas, M.;
Lebus, S.; Wortmann, R. Chem. sEur. J . 1997, 3, 1091-1104. (e)
Marder, S. R.; Kippelen, B.; J en, A. K. Y.; Peyghambarian, N. Nature
1997, 388, 845-851. (f) Cheng, T. R.; Huang, C. H.; Gan, L. B.; Luo,
C. P.; Yu, A. C.; Zhao, X. S. J . Mater. Chem. 1998, 8, 931-935. (g)
Shu, C. F.; Wang, Y. K. J . Mater. Chem. 1998, 8, 833-835.
* To whom correspondence should be addressed. Fax: (+39) 026
448 5403.
(1) (a) Williams, D. J . Angew. Chem., Int. Ed. Engl. 1984, 23, 690-
703. (b) Chemla, D. S.; Zyss, J . Nonlinear Optical Properties of Organic
Molecules and Crystals; Academic Press: New York, 1987. (c) Prasad,
P. N.; Williams, J . Introduction to Nonlinear Optical Effects in
Molecules and Polymers; Wiley: New York, 1991.
(2) (a) Marder, S. R.; Perry, J . W. Adv. Mater. 1993, 5, 804-815.
(b) Marder, S. R.; Perry, J . W. Science 1994, 263, 1706-1707. (c)
Bredas, J . L. Science 1994, 263, 487-488. (d) Drost, K. J .; J en, A. K.
Y.; Rao, V. P. CHEMTECH 1995, 25, 16-25. (e) Marks, T. J .; Ratner,
M. A. Angew. Chem., Int. Ed. Engl. 1995, 34, 155-173. (f) Dalton, L.
R.; Harper, A. W.; Ghosn, R.; Steier, W. H.; Ziari, M.; Fetterman, H.;
Shi, Y.; Mustacich, R. V.; J en, A. K. Y.; Shea, K. J . Chem. Mater. 1995,
7, 1060-1081. (g) Verbiest, T.; Houbrechts, S.; Kauranen, M.; Clays,
K.; Persoons, A. J . Mater. Chem. 1997, 7, 2175-2189. (h) Wu¨rthner,
F.; Yao, S.; Schilling, J .; Wortmann, R.; Redi-Abshiro, M.; Mecher, E.;
Gallego-Gomez, F.; Meerholz, K. J . Am. Chem. Soc. 2001, 123, 2810-
2824 and references 18a and 20 therein.
(4) Matyushov, D. V.; Schmid, R.; Ladanyi, B. M. J . Phys. Chem. B
1997, 101, 1035-1050.
(5) (a) Dehu, C.; Meyers, F.; Hendrickx, E.; Clays, K.; Persoons, A.;
Marder, S. R.; Bredas, J . L. J . Am. Chem. Soc. 1995, 117, 10127-
10128. (b) Zuliani, P.; Delzoppo, M.; Castiglioni, C.; Zerbi, G.; Marder,
S. R.; Perry, J . W. J . Chem. Phys. 1995, 103, 9935-9940. (c) Thompson,
W. H.; Blancharddesce, M.; Hynes, J . T. J . Phys. Chem. 1998, 102,
7712-7722. (d) Bartkowiak, W.; Lipinski, J . J . Phys. Chem. A 1998,
102, 5236-5240. (e) Lipinski, J .; Bartkowiak, W. Chem. Phys. 1999,
245, 263-276. (f) Albert, I. D. L.; Marks, T. J .; Ratner, M. A. J . Phys.
Chem. 1996, 100, 9714-9725. (g) Allin, S. B.; Leslie, T. M.; Lumpkin,
R. S. Chem. Mater. 1996, 8, 428-432. (h) Painelli, A.; Terenziani, F.
Synth. Met. 2000, 109, 229-233. (i) Baur, J . W.; Alexander, M. D.;
Banach, M.; Denny, L. R.; Reinhardt, B. A.; Vaia, R. A.; Fleitz, P. A.;
Kirkpatrick, S. M. Chem. Mater. 1999, 11, 2899-2906.
10.1021/jo015937c CCC: $20.00 © 2001 American Chemical Society
Published on Web 12/04/2001

8884 J . Org. Chem., Vol. 66, No. 26, 2001
Abbotto et al.
1, which can be described in terms of the contribution of
two-limit forms, 1-A and 1-B (zwitterionic and neutral,
respectively). We show how it is possible to finely tune
the intramolecular charge transfer and π-electron dis-
tribution by varying the nature of the electron-withdraw-
ing groups (EWG), the bridging site (X), and the solvent
polarity. Properly adjusting the relative contribution of
these three factors makes it possible to access a whole
range of π-electron structures, which should ultimately
lead to a finely tuned spectrum of electronic structure
dependent properties.
pyridine, the negative charge is preferably delocalized
onto Y, with the heteroaromatic ring being in the
aromatic form (low double-bond character between C(4)
and C- and isochrony of C(3) and C(5)). Conversely, when
Y is weaker than pyridine, charge transfer takes place
from the negative center to the ring, leading to a
negatively charged quinoid form of the heterocycle.
Our investigation of charge distribution in aza-
heterocyclic species is based on the exploitation of
13C and 15N NMR spectroscopy and application of shift/
π-electron density relationships.9 Relationships 113 and
211,12,14 allow empirical access to the relative π-electron
densities (∆qπ, electrons), once the difference between
their chemical shifts is measured (∆δ, ppm), for each pair
of carbon or nitrogen atoms belonging to two compounds
of the same series, where corresponding sites have the
same hybridization character but different substitution
patterns. In this manner, it is possible to quantitatively
compare the π-electron distribution in a homogeneous
series of compounds with respect to a reference system,
the proper figures of merit of which are clearly estab-
lished.
We chose to design pyridine-based push-pull chro-
mophores because this ring has widely been shown to
represent a key factor in the design of efficient organic
materials.1,6-8 However, it should be noted that, with few
exceptions, the ring is reported exclusively in its more
common aromatic form.
∆δ13C ) -160∆qπ
∆δ15N ) -366∆qπ
(1)
(2)
C
N
Within our multiyear investigation on the π-electron
properties of π-deficient and π-excessive heteroaromatic
rings,9 we have already established the strong electron-
withdrawing nature of the pyridinyl substituent:10 this
group is highly ranked among primary electron-with-
drawing organic functionalities and π-deficient hetero-
aromatics. Its electron-withdrawing power is comparable
to that of carbonyl and carboxyl functionalities and
is much higher than that of common acceptor moieties
such as cyano,11 sulfones, and sulfoxide.12 In particular,
we investigated the geometric isomerism exhibited by
a series of 4-picolyl carbanions, where the 4-pyridyl
(4-Py) moiety was used as a probe to quantitatively
rank the electron-withdrawing properties of primary
organic functionalities.12 The anisochrony of C(3) and
C(5) carbon atoms of the pyridine ring in the series
4-Py-CH--Y was used to probe the double-bond charac-
ter between C(4) and the carbanionic carbon, and thus
the charge partitioning between the 4-pyridyl and Y
groups. Consequently, when Y is a stronger acceptor than
With these premises, we chose to consider for the
present work the pyridine-based push-pull derivatives
2-9. In the series 2-4, we consider N-aryl substituted
1-methyl-4-pyridoneimines, therefore setting the bridging
unit X equal to N. Going from 2 to 4, one finds that
the aryl substituent is increasingly more electron-
withdrawing. Compounds 5 and 6 are the CH-analogues
of pyridoneimines 3 and 4, with X ) CH. Finally, in
compounds 7 and 8, we replaced the electron-poor aryl
moiety of 3 and 4 with the SO2 group, giving rise to the
deprotonated form of sulfonamides. In compound 9 of the
sulfonamide series, the electron-withdrawing capacity of
the pyridyl ring is increased by derivatizing the pyridic
nitrogen atom with the strong acceptor 2,4-dinitrophenyl
substituent. The compounds were investigated by means
of multinuclear NMR and electronic spectroscopy. Geo-
metric isomerism and π-charge distribution have been
used in order to determine their π-electron structure and
the contribution of the two limit forms 1-A and 1-B to
describe their ground state. Finally, we have taken into
account the role of the surrounding media by investigat-
ing all of the systems in two solvents of different polarity,
CHCl3 and DMSO. According to the well-known ET(30)
Reichardt’s polarity scale,15 CHCl3 (ET ) 39.10) is middle
ranked, whereas DMSO (ET ) 45.10) is a highly polar
solvent, ranked lower than only alcohols and water.
(6) (a) Characterization Techniques and Tabulations for Organic
Nonlinear Optical Materials; Kuzyk, M. G., Dirk, C. W., Eds.; Marcel
Dekker: New York, 1998. (b) Bosshard, C.; Sutter, K.; Preˆtre, P.;
Hulliger, J .; Flo¨rsheimer, M.; Kaatz, P.; Gu¨nter, P. In Organic
Nonlinear Optical Materials - Advances in Nonlinear Optics; Garito,
A. F., Kajzar, F., Eds.; Gordon and Breach: Basel, 1995; Vol. 1.
(7) Pyridine-based push-pull chromophores were used in a number
of recent organic photorefractive materials: (a) Lundquist, P. M.;
Wortmann, R.; Geletneky, C.; Twieg, R. J .; J urich, M.; Lee, V. Y.;
Moylan, C. R.; Burland, D. M. Science 1996, 274, 1182-1185. (b)
Wortmann, R.; Glania, C.; Kramer, P.; Lukaszuk, K.; Matschiner, R.;
Twieg, R. J .; You, F. Chem. Phys. 1999, 245, 107-120.
Resu lts
Syn th esis. To the best of our knowledge, the substi-
tuted pyridoneimine series 2-4 was previously unknown
in the literature. The parent compound 2 was prepared
(8) Reinhardt, B. A.; Brott, L. L.; Clarson, S. J .; Dillard, A. G.; Bhatt,
J . C.; Kannan, R.; Yuan, L. X.; He, G. S.; Prasad, P. N. Chem. Mater.
1998, 10, 1863-1874.
(9) See: Abbotto, A.; Bradamante, S.; Facchetti, A.; Pagani, G. A.
J . Org. Chem. 1999, 64, 6756-6763 and references therein.
(10) (a) Berlin, A.; Bradamante, S.; Pagani, G. A. J . Chem. Soc.,
Perkin Trans. 2 1988, 1525-1530. (b) Bradamante, S.; Pagani, G. A.
Pure Appl. Chem. 1989, 61, 709-716. (c) Abbotto, A.; Bradamante, S.;
Pagani, G. A.; Rzepa, H.; Stoppa, F. Heterocycles 1995, 40, 757-776.
(11) Abbotto, A.; Bradamante, S.; Pagani, G. A. J . Org. Chem. 1993,
58, 449-455.
(13) (a) Bradamante, S.; Pagani, G. A. J . Org. Chem. 1984, 49,
2863-2870. (b) Bradamante, S.; Pagani, G. A. J . Chem. Soc., Perkin
Trans. 2 1986, 1035-1046.
(14) (a) Abbotto, A.; Alanzo, V.; Bradamante, S.; Pagani, G. A. J .
Chem. Soc., Perkin Trans. 2 1991, 481-488. (b) Gatti, C.; Ponti, A.;
Gamba, A.; Pagani, G. A. J . Am. Chem. Soc. 1992, 114, 8634-8644.
(15) (a) Reichardt, C. Chem. Soc. Rev. 1992, 21, 147. (b) Reichardt,
C. Chem. Rev. 1994, 94, 2319.
(12) Abbotto, A.; Bradamante, S.; Pagani, G. A. J . Org. Chem. 1993,
58, 444-448.

Pyridoneimines and Pyridonemethides
J . Org. Chem., Vol. 66, No. 26, 2001 8885
Sch em e 1
which was reported in very few cases.20 The general
procedure we have followed for the synthesis of 7 and 8
implied condensation of the amine 12 with the proper
sulfonyl chloride. If the reaction is carried out in the
presence of a base, the zwitterions 7 and 8 are directly
formed, with no isolation of the intermediate sulfonamide
salts (Scheme 3). Tosyl derivative 8 may alternatively
be obtained, with lower yields, by deprotonation with
sodium hydride of the tosylamide 1420a of 4-amino pyri-
dine and subsequent alkylation (Scheme 4). The last step
proceeds fully regioselectively on the pyridic nitrogen of
the bidentate nucleophilic anion 15 when methyl triflate
is used as an alkylating agent. The same intermediate
14 is used for the synthesis in good yields of the
dinitrophenyl derivative 9, via regioselective arylation of
the anion 15 with 2,4-dinitrofluorobenzene (Scheme 4).
NMR Ch a r a cter iza tion : Geom etr ic Isom er ism
a n d Bon d Or d er Tu n in g. The 13C and 15N chemical
shifts of compounds 2-9 are collected in Table 1. The
NMR analysis of pyridoneimines 2-4 and pyridone-
methides 5 and 6 was carried out in DMSO and CHCl3.
In some cases, the low solubility in the less polar solvent
prevented the recording of their 15N chemical shifts.
Solubility in CHCl3 of sulfonamides 7-9 was even lower,
so 13C and 15N shifts were recorded only in DMSO.
However, to investigate geometric isomerism (vide infra)
by alkylation of 4-anilinopyridine (10),16 followed by de-
protonation with potassium hydroxide of the pyridinium
salt 11 (Scheme 1). The latter was previously reported
just as iodide in a few patents.17 The last step afforded a
crude oil that, after distillation in a Kugelrohr apparatus
at 5 × 10-3 mmHg, gave 2 as a low-melting yellow solid.
The corresponding iodide17 of the pyridinium salt 11 can
be prepared from 10 and methyl iodide, but the reaction
is sluggish and yields are much lower. Alternatively, the
salt 11 may be obtained by nucleophilic substitution of
4-bromo-1-methylpyridinium triflate with aniline and
using Et3N as a base. However, also in this case, yields
are not satisfactory and purification from byproducts
(triethylammonium salts or excess aniline) is tedious and
seldom successful.
1
in two differently polar solvents, H and 13C shifts were
obtained in acetone, the ET value of which (42.20)15 is
middle ranked between those of DMSO and chloroform.
The anisochrony of C(3) and C(5) carbon atoms, as well
as H(3) and H(5) hydrogen atoms, of the pyridine ring is
the most direct evidence of the predominant contribution
of the quinoid limit formula 1-B with respect to the
aromatic form 1-A. As can be seen from the values of
Table 1, the anisochrony of the 3 and 5 positions of
the pyridine ring was observed in only two cases, that
is, in the unsubstituted pyridoneimine 2 and the nitro-
phenylpyridonemethide 5. In all of the other cases, the
corresponding positions of the heterocyclic ring have the
same chemical shifts.
Nucleophilic substitution of 4-amino-1-methylpyri-
dinium triflate 12 with 4-nitrofluorobenzene and 2,4-
dinitrofluorobenzene led to the mono- and dinitro-
derivatives 3 and 4, respectively (Scheme 2). In the
latter case, formation of the disubstitution coproduct
13 was observed, in relative amounts depending on tem-
perature and reaction stoichiometry. The two products
4 and 13 could be separated by column chromatography
on neutral alumina. In the reaction with dinitrofluoro-
benzene, potassium carbonate was sufficient as a base,
but stronger basic conditions were needed for the sub-
stitution with mononitrofluorobenzene.
The aromatic region of the 13C NMR spectrum of
compound 2 in CHCl3 at 243 K is shown in Figure 1. The
higher-field values of positions 3 and 5 in compounds 2
and 5 were assigned to the position facing (cis) the phenyl
ring due to known compression effects21 operating on
similar systems. Indeed, in the anion of 4-benzylpyridine,
the phenyl group induces a shielding of ca. 9-10 ppm
on the carbon atom of the heterocycle cis to it.10a Both
Corresponding CH-analogues 518 and 619 were prepared
according to literature methods, with slight modifications.
Sulfonamido derivatives 7-9 were previously unknown
in the literature, with the exception of the tosylate 8,
(20) (a) Kravtsov, D. N.; Nesmeyanov, A. N. Izv. Akad. Nauk, Ser.
Khim. 1967, 5, 1024-1030; Chem. Abstr. 1967, 67, 64497h. (b) Boberg,
F.; Nink, G.; Bruchmann, B.; Garming, A. Phosphorus, Sulfur Silicon
Relat. Elem. 1991, 57, 235-247. (c) Boberg, F.; Bruchmann, B.; Nink,
G.; Garming, A. Phosphorus, Sulfur Silicon Relat. Elem. 1989, 44, 267-
284.
(21) (a) Bank, S.; Dorr, R. J . Org. Chem. 1987, 52, 501. (b)
Bushweller, C. H.; Sturges, J . S.; Cipullo, M.; Hoogasian, S.; Gabriel,
M. W.; Bank, S. Tetrahedron Lett. 1978, 1359.
(16) Petrow, V. A. J . Chem. Soc. 1945, 927-928.
(17) (a) Chem. Abstr. 1979, 90, 187180. (b) Chem. Abstr. 1973, 79,
105070. (c) Chem. Abstr. 1973, 78, 159445.
(18) (a) Preussmann, R.; Hengy, H.; Druckrey, H. J ustus Liebigs
Ann. Chem. 1965, 684, 57. (b) Geissman, T. A.; Hochman, H.; Fukuto,
R. T. J . Am. Chem. Soc. 1952, 74, 3313.
(19) Hiroaka, H. Bull. Chem. Soc. J pn. 1966, 39, 380.

8886 J . Org. Chem., Vol. 66, No. 26, 2001
Abbotto et al.
Sch em e 2
Sch em e 3
DMSO, suggesting that in this solvent the aromatic form
is further stabilized with respect to the other one. In the
remaining compounds, only one set of sharp signals was
recorded and thus the formula 1-A is the best descriptor
for their electron structure.
Va r ia ble-Tem p er a tu r e Exp er im en ts a n d Activa -
tion P a r a m eter s. The fact that the parent compound 2
has a quinoid structure is of significant interest because,
by setting this system as a reference, we have been
provided with a basis for discriminating neutral-quinoid
from aromatic-zwitterionic structures. Consequently, we
have decided to perform a detailed NMR investigation
of rotameric equilibria in solvents of different polarity
(DMSO and CHCl3) and at different temperatures. The
most representative set of spectra related to this study
Sch em e 4
1
is shown in Figure 2. The H NMR analysis shows that
the pyridine proton shifts are indeed sensitive to tem-
perature and solvent effects. NMR anisochronies of
positions 3 and 5 and positions 2 and 6 are observed at
243 K in the less polar solvent CHCl3. Under these
conditions, signals are sharp and well resolved. By
raising the temperature to room temperature, aniso-
chrony is still present but broadening of signals is now
observed. When spectra are recorded in the highly polar
solvent DMSO, broadening is further enhanced with the
temperature (295 K) being now close to coalescence
conditions. In fact, in this solvent, signals ascribed to
positions 3 and 5 collapse at 313 K into one single broad
pattern (not represented in Figure 2). At higher temper-
atures (363 K), positions 2 and 6 and positions 3 and 5
are equivalent and each is responsible for a sharp
doublet, showing that under these conditions, free rota-
tion along the bond linking C(4) of the heterocycle and
the nitranionic bridge is occurring. The pattern assign-
ment of the aromatic systems of 2 has been obtained from
COSY NMR experiments. Again, as described above for
carbon atoms, we have assigned the most shielded
resonances to protons cis to the phenyl ring because of
compression effects.
data of Table 1 and the spectrum of Figure 1 clearly prove
that in compounds 2 and 5, a high double-bond character
between C(4) of the heterocycle and the bridging atoms
is present, leading to hindered rotation around the same
bond. In other terms, it is firmly established that for
these systems, the ground state is predominantly de-
scribed by the quinoid form 1-B. Hindered rotation
between C(4) and the bridging unit is also present in
compound 6, as evidenced by the broadening of the C(3)
and C(5) signals in CHCl3. However, in this case, only
one value has been recorded for both positions, demon-
strating that the contribution of the aromatic form 1-A
is slightly predominant, although the quinoid form is
important in the description of the ground state. Broad-
ening of signals disappears in the spectrum recorded in
We have performed similar variable-temperature ex-
periments on the representative set of compounds 3, 5,
6, and 9, focusing once more our attention on the
isochrony/anisochrony of protons of the azine ring. We
1
have recorded H NMR spectra at 10 K intervals using
different solvents depending on the coalescence temper-
ature TC of the considered compounds. When H(3) and
H(5) are nonequivalent at room temperature, which is
the case of the unsubstituted pyridoneimine 2 and
mononitrophenyl pyridonemethide 5, investigation was

Pyridoneimines and Pyridonemethides
Ta ble 1. 13Ca a n d 15Nb NMR Sh ifts (p p m ) of Com p ou n d s 2-9 a t 298 K
pyridine ring positions
phenyl ring positionsc
C(4) C(5) C(6) N/CHe C(1′) C(2′) C(3′) C(4′) C(5′) C(6′)
240.0
J . Org. Chem., Vol. 66, No. 26, 2001 8887
compd solventd N(1) C(2)
C(3)
other
2
2
3
3
4
4
5
5
6
6
7
7
8
DMSO 126.5
f
CHCl3
137.5g 106.8g 156.8 115.6 138.6
151.1 121.89 129.2 121.92 129.2 121.89 CH3 ) 42.7
DMSO 137.4 140.7 111.4 155.0 111.4 140.7 236.2 156.9 121.2 125.5 139.6 125.5 121.2 CH3 ) 42.5; NO2 ) 370
CHCl3
127.0 138.9 112.2 159.7h 112.2 138.9 234.0 157.2h 121.7 125.5 141.5 125.5 121.7 CH3 ) 43.0; NO2 ) 369
DMSO 147.2 141.6 112.6 158.6 112.6 141.6 226.0 152.8 141.0i 121.6 136.8i 127.6 122.2 CH3 ) 43.1; NO2 ) 366, 372
CHCl3
f
139.3 112.4 157.5 112.4 139.3
152.9 141.5j 122.2 140.1j 128.0 125.2 CH3 ) 43.4
DMSO 131.6 138.3 108.1 141.4 116.9 135.7 100.3 148.3 123.3 124.3 138.6 124.3 123.3 CH3 ) 41.8; NO2 ) 369
f
CHCl3
136.3g 108.1g 133.7 116.7 133.7 102.4 148.2 124.6k 124.7k 136.3 124.7k 124.6k CH3 ) 42.2
DMSO 153.9 139.9 116.9 148.6 116.9 139.9
97.6 140.2 138.2 123.8 135.0 125.4 123.8 CH3 ) 43.5; NO2 ) 372, 366
98.2 141.8 142.5 123.3 139.4 126.2 125.5 CH3 ) 43.1
137.0 114l
144.8 114l 137.0
f
CHCl3
DMSO 170.0 143.9 117.2 162.1 117.2 143.9 160.3
CH3 ) 44.9; CF3 ) 120.7
CH3 ) 45.6; CF3 ) 122.0
CH3 ) 43.7;m tolyl
acetonef
DMSOf
144.1 118.3 164.5 118.3 144.1
142.1 115.0 161.3 115.0 142.1
positions: 141.2, 140.8,
129.0 (2C), 126.0 (2C), 20.8
9
DMSO 156.9 141.0 114.9 162.1 114.9 141.0 151.2
NO2 ) 361, 363;
dinitrophenyl: 147.7, 143.6,
139.4, 131.6, 129.7, 121.6;
tolyl: 141.7, 140.5, 129.7
(2C), 126.1 (2C), 20.9
9
acetonef
141.6 116.8 165.4 116.8 141.6
dinitrophenyl: 150.6, 146.0,
141.6, 134.1, 131.1, 123.4;
tolyl: 143.3, 143.1, 130.6
(2C), 128.0 (2C), 22.0
a
b
d
Relative to Me4Si (0.0 ppm). Relative to liquid NH3 (0.0 ppm). c Phenyl ring directly bonded to N or CH bridge. Solvents are
deuterated. e Relative to the imine or the methine bridge. f 15N shifts not available due to the low solubility of the compound. Positions
g
cis to the phenyl ring (phenyl compression effect, ref 21). Values can be exchanged. Values can be exchanged. j Values can be exchanged.
h
i
k
l
m
Values can be exchanged. Broad. Methyl bonded to pyridine nitrogen.
F igu r e 1. Aromatic region of the 13C NMR spectrum of
compound 2 in CHCl3 (T ) 243 K).
performed in DMSO by raising the temperature above
298 K. In the remaining systems, since the pyridine
protons are equivalent at room temperature, spectra had
to be recorded at lower temperatures in different solvents.
For the sake of homogeneity with 13C NMR data collected
in Table 1, we have used CHCl3 and acetone for com-
pounds 6 and 9, respectively. The low TC of the dinitro-
phenyl pyridoneimine 4 inhibited us from performing this
analysis in CHCl3, and a low-melting solvent mixture
such as CH2Cl2/CHCl3 had to be used. From the experi-
mentally obtained TC values and peak separations ∆ν (in
Hertz) of nonequivalent H(3) and H(5) atoms, the activa-
tion energies ∆Gq of the rotational process along the C(4)-
bridge bond were obtained by applying eq 3.22 When
possible, peak separation was taken at the highest
possible temperature where anisochronous sharp signals
F igu r e 2. Variable-temperature 1H NMR spectra of com-
pound 2 in CHCl3 and DMSO (aromatic region).
are observed for H(3) and H(5). For compound 2, two
broad signals at 5.94 and 6.05 ppm for H(3) and H(5),
respectively, were recorded in DMSO at 295 K, corre-
sponding to a separation of 55.0 Hz. The high melting
point of DMSO prevented lower-temperature NMR stud-
ies. All of the relevant data on variable-temperature
experiments and activation parameters are collected in
Table 2.
∆Gq (kcal/mol))(4.575 ×10-3)TC[9.97 +log(TC/∆ν)] (3)
Solva t och r om ic Da t a : Zw it t er ion ic vs Neu t r a l
(22) Gu¨nther, H. NMR Spectroscopy. An Introduction; J . Wiley and
Sons: Chichester, 1980; p 247.
St r u ct u r e. Solvatochromism, defined as the solvent

8888 J . Org. Chem., Vol. 66, No. 26, 2001
Abbotto et al.
Ta ble 2. Va r ia ble-Tem p er a tu r e Da ta a n d Exp er im en ta l
Activa tion P a r a m eter s for Com p ou n d s 2, 3, 5, 6, a n d 9
Rela tive to th e Rota tion a l P r ocess a lon g th e C(4)-Br id ge
Bon d
character is maintained for each couple of solvents
considered. Since this is not always the case for the
systems of the present work, solvatochromic results are
to be cautiously treated and always in conjunction with
the NMR results, where the effects of solvents with
different polarity are separated.
compd
solvent
DMSO
TC (K)a ∆ν (Hz)b ∆Gq (kcal/mol-1
)
2
3
5
6
9
313
180
333
290
240
55.0
6.6
15.4
9.4
CH2Cl2/CHCl3 8:1
DMSO
CHCl3
7.8
29.8
44.4
17.7
14.5
11.8
Discu ssion
acetone
a
Pertinent conclusions of our investigation on intramo-
lecular charge transfer, geometric isomerism, and there-
fore bond order, can be reached from both qualitative and
quantitative perspectives. From the qualitative point of
view, the target is to establish the relative importance
of the two limit forms 1-A and 1-B in the description of
the ground state of chromophores 2-9. The most direct
evidence is the presence of geometric isomerism due to a
double-bond character between the bridging atom and
C(4) of the pyridine ring, which leads to anisochrony of
the corresponding positions of the heterocycle. Data of
Table 1 indicate that compounds 2 and 5, for which C(3)
and C(5) are anisochronous, are better described by the
quinoid structure 1-B. The dinitrophenyl analogue of 5,
compound 6, is borderline located between an aromatic
and quinoid-like structure. In this case, the solvent plays
a key role in the description of the electronic nature of
the ground state: whereas in the more polar DMSO the
zwitterionic form is stabilized, leading to a single reso-
nance for the 3 and 5 positions, decreasing the polarity
of the media increases the importance of the quinoid
form, as evidenced by the broadening of the correspond-
ing NMR signals. These results are consistent with the
solvatochromic study, for which a shorter wavelength
shift from DMSO to CHCl3 is observed for 5 and 6, thus
suggesting that the quinoid character is predominant.
In light of the above comments, conclusions reached
thus far are almost qualitative. Although the value of
solvatochromism can be used in principle as a quantita-
tive probe, the borderline nature of some systems or the
solvent polarity dependence of their electronic structure
does not allow clear-cut conclusions to be reached in most
of the cases. Table 3 clearly shows that a definite trend
of the value of λmax within the ET polarity scale cannot
be extrapolated, leading to uncertainty in most of the
cases. For these reasons, our quantitative method of
choice relies on the analysis of 13C and 15N chemical shift
and their translation into π-electron densities by means
of eqs 1 and 2.
Coalescence temperature of H(3) and H(5) NMR shifts of the
b
pyridine ring. Peak separation of anisochronous H(3) and H(5)
of the pyridine ring (500 MHz NMR instrument).
Ta ble 3. Solva toch r om ic Da ta [λm a x (n m )] of
Ch r om op h or es 3-9 in Selected Solven ts
solvent
ET
3
4
5
6
7
8
9
MeOH
CH3CN 45.6 432
DMSO
DMF
acetone 42.2 432
55.4 408a 427 545 577 284 299 303
449 554 580 286 304 356
466 588 594 287 307 305
45.1 457
43.2 448
460 569 589 288 307 305-357
447 549 578 356
429 541 580 295 310 305-366
b
b
CHCl3
39.1 412
a
A NaOH pellet was added to the solution in order to prevent
b
protonation of the anionic bridging unit. Covered by solvent
absorption band.
dependence of the UV-vis absorption spectrum of a
molecule, provides a fast and useful qualitative method
for determining the zwitterionic or neutral nature of
push-pull systems such as the ones investigated in the
present work.23 Table 3 collects absorption data relative
to the charge transfer (CT) band in a selected number of
solvents, for which ET values are reported.15 Pyridone-
imines and pyridonemethides 3-6 present a clear CT
band in the visible region of the spectrum, whereas
energy of the electronic absorption of sulfonamido deriva-
tives 7-9 falls in the UV region. Due to the strong
polarity of the protic solvent MeOH, which stabilizes the
zwitterionic character 1-A of the chromophores 3-6 and,
thus, the anionic nature of the bridging unit X, the
absorption spectrum was recorded in this solvent with
addition of a NaOH pellet, to prevent back-protonation
to the precursor salt.
Within the common interpretation of solvatochromic
interactions,23 a shorter wavelength shift of the CT band
with increasing the solvent polarity indicates a larger
value of the molecular dipole moment in the ground state
with respect to that of the excited state. In our case, this
is in agreement with a zwitterionic nature of the
former: in fact, the transition to the excited state,
corresponding to an intramolecular CT phenomenon,
would lead to a quinoid structure, associated with a
smaller dipole moment. Besides other factors that can
affect the values of solvatochromism (e.g., aggregation),23
one source of uncertainty of this type of analysis concerns
whether the sign of the shift of the absorption spectrum
has to do with the zwitterionic or neutral character of
the dye. Indeed, this is true only when the various
solvents considered do not dramatically affect the elec-
tronic nature of the ground state. In other terms, conclu-
sions of the solvatochromic study are, in principle, valid
only when the predominant zwitterionic, or neutral,
The amount of π-electron density residing on the
pyridine nitrogen atom is undoubtedly the most evident
quantitative probe for determining the extent of the
intramolecular charge transfer. However, in the perspec-
tive of the aim of our study, it is not important its
absolute value but rather the relative differences within
the investigated series and the comparison with proper
pyridine-based systems for which the π-electron structure
is known or intrinsically evident. We have decided to
introduce the parent pyridinium salt 1624 and the pyri-
doneimine derivative 1725 as limit-representative systems
(24) 15N chemical shift of N-methylpyridinium iodide (16) (DMSO,
1 M) ) 200 ppm: Witanowski, M.; Stefaniak, L.; Webb, G. A. In Annual
Reports on NMR Spectroscopy; Webb, G. A., Ed.; Academic Press:
London, 1986; Vol. 18, p 504.
(23) (a) Reichardt, C. Solvent Effects in Organic Chemistry; Verlag:
New York, 1979; Chapter 6. (b) Suppan, P.; Ghoneim, N. Solvato-
chromism; The Royal Society of Chemistry: Cambridge, 1997. (c)
Liptay, W. Angew. Chem., Int. Ed. Engl. 1969, 8, 177-188.
(25) 14N chemical shift (pyridine nitrogen atom) of 1-methyl-1H-
pyrid-4-one-imine (17) (acetone) ) 120 ppm: Stefaniak, L. Org. Magn.
Reson. 1979, 12, 379.

Pyridoneimines and Pyridonemethides
J . Org. Chem., Vol. 66, No. 26, 2001 8889
F igu r e 3. Bar graphs of 15N NMR chemical shifts (A) and π-electron densities data (B) for pyridine (black) and imine (gray)
nitrogen atoms, respectively, of compounds 2-7, 9, 12, 16, and 17. Molecules are ordered from neutral-quinoid to zwitterionic-
aromatic character. Each compound is drawn according to the most relevant limit formula descriptor. Shown figures of π-positive
and π-negative charge increments (increasing charge separation; values in millielectrons) are calculated with respect to quinoid
compound 2 as a reference (ref). Chemical shift values are taken from Table 1 (DMSO) and converted to π-electron density variations
through eq 2.
of the structures 1-A and 1-B, respectively. We have also
included, for comparison, compound 12 as an example
of a pyridinium salt bearing a strong, but not anionic,
donating group in the para position. 15N NMR data and
relative π-electron densities of pyridine and, when ap-
plicable, imine nitrogen atoms are shown in Figures 3A
and 3B, respectively. Compounds are drawn in their
aromatic or quinoid preferred form depending on the
recorded isochrony or anisochrony of the carbon atoms
of the pyridine ring (see Table 1). It is gratifying for the
eye to observe in Figure 3 that the azinium nitrogen site
experencies a low-field shift on going from the pyridone-
imines 17 and 2 to the pyridinium cation 16, showing a
monotonic increase of positive π-charge and, therefore,
an increasingly larger importance of the pyridinium
character 1-A. In other terms, the trend in the 15N
chemical shift is able to quantitatively probe the π-dona-
tion from the cyclic nitrogen atom to the bridging unit.
On the other hand, a high-field shift of the nitrogen
bridge is observed from 2 to 7, consistent with a simul-
taneous increase of π-negative charge and, therefore,
charge separation. Within the series of molecules here
investigated, we can conclude that the strongest neutral-
quinoid character is associated with imine 2, whereas
sulfonamido derivative 7 owns the largest zwitterionic
nature.
15N NMR analysis of pyridine N(1) and, where possible,
of the imine nitrogen atom revealed that the qualitative
conclusions, as derived from the presence of geometric
isomerism and solvatochromic data, are fully consistent
with the quantitative trend of intramolecular charge
transfer. Unfortunately, the analysis of the π-electron
density of the bridging unit cannot be extended to the
carbanions 5 and 6, due to the fact that eq 1, in the
present form, can only be applied for comparing two
carbon atoms having the same substitution pattern.13

8890 J . Org. Chem., Vol. 66, No. 26, 2001
Abbotto et al.
F igu r e 4. Bar graphs of π-electron density variation for pyridine CH carbon atoms of compounds 2-9. Systems are sorted as in
Figure 3. Shown figures of π-positive charge increments (millielectrons) are calculated with respect to corresponding positions of
quinoid system 2 as a reference (ref). Values are obtained from eq 1 using 13C chemical shifts reported in Table 1 (DMSO, when
available).
13C NMR analysis, and their translations into relative
π-electron densities, of the CH pyridine carbon atoms
reveal that a significant portion of the positive π-charge
increment (increase of charge separation) on going from
the quinoid compound 2 to the zwitterionic compound 7
involves the carbon framework of the heterocyclic ring
(Figure 4). The quantitative trend of the increase in
charge separation is once again in full agreement with
the whole situation so far depicted.
are shown in Figure 2. Comparing the spectra at 295 K
in the two solvents reveals how the anisochrony of the
pyridine protons in CHCl3 is still present in DMSO but
signals move from rather defined doublets to broad
patterns, as a consequence of the increased contribution
of the zwitterionic form and thus of the decrease of the
rotational barrier along the C(4)-N bond. However, in
this case, as in all of the others, the solvent effect alone
is not able to swap over the relative contribution of the
two structures. To achieve this result, solvent and
substituent control must be operating simultaneously. A
similar behavior is observed for pyridine carbon shift of
6. For this compound, isochronous C(3) and C(5) signals
shift from broad to resolved patterns on going from CHCl3
to DMSO, in agreement with an improved contribution
of form 1-A to the description of the ground state in the
latter solvent.
It is evident how the presence of the function SO2R
stabilizes the negative charge on the nitranionic center,
with respect to the pyridoneimines 2-4, increasing the
weight of the zwitterionic character in the description of
the ground state. These results therefore suggest that
the SO2R is able to stabilize a negative charge in the R
position with limited delocalization onto itself, as we have
previously reported for a number of anionic derivatives
bearing this group directly linked to the negative
center.11,13b,26 As far as pyridoneimines 2-4 are con-
cerned, the extent of intramolecular charge transfer
increases by decreasing the electron-withdrawing power
of the aryl moiety substituting the exocyclic nitrogen
atom. When the strong dinitrophenyl group is present,
the negative charge on the imine center is stabilized,
likely also for resonance effects, and is not available for
donation to the heterocyclic ring. In compound 2, the
nitranionic center does not have any stabilizing factors
other than delocalizing a significant part of the charge
to the azine (and most of it to the N(1) atom), leading to
a stable quinoid form. It is rewarding to find that in this
series of compounds the increasing electron-withdrawing
character of the aryl group on going from 2 to 4 does not
diminish the negative charge in its R positions. In other
terms, the imine nitrogen experiences a high-field shift
on going from 2 to 4, consistent with a larger π-electron
density. These findings lead us to conclude that the main
intramolecular charge-transfer mechanism involve the
anionic central group and the pyridine ring, with coop-
erative effects of the other substituents.
Con clu sion
On the basis of multinuclear NMR analysis and
exploitation of shift/π-electron density relationships, ac-
companied by solvatochromic data, we have provided
evidence of how it is possible to finely tune the extent of
intramolecular charge transfer, and thus electron struc-
ture, in a series of pyridine-based push-pull chromo-
phores by properly playing with substituent and solvent
effects.
Results relative to compounds 2-9 can be schemati-
cally summarized as follows. (1) Sulfonamido derivatives
7-9 are better described by the charge-separated struc-
ture 1-A, thanks to the ability of the -SO2- functionality
to stabilize a negative charge R to itself. (2) If the other
substituent effects are taken as constant, the nitranionic
bridge stabilizes the form 1-A with respect to a carban-
ionic moiety. This result is evidently associated with the
higher ability of the nitrogen atom to accept negative
charge with respect to a carbon atom, because of its
higher electronegativity; so, pyridoneimine 3 exists preva-
lently as aromatic-zwitterionic form, but the corre-
sponding pyridonemethide 5 has a clear quinoid char-
acter. (3) Electron-withdrawing aryl substituents on the
bridging atom favor the presence of a higher π-electron
density on this site but do not significantly decrease it
by delocalization; as a consequence, charge-separated
structures are favored. As an example, dinitrophenyl-
The role of the polar solvent DMSO is that to stabilize,
as expected, the charge separated structure 1-A with
respect to the less polar CHCl3. The most striking effect
was found for compound 2, for which 1H NMR spectra
(26) Barchiesi, E.; Bradamante, S.; Ferraccioli, R.; Pagani, G. A. J .
Chem. Soc., Perkin Trans. 2 1990, 375-383.

Pyridoneimines and Pyridonemethides
J . Org. Chem., Vol. 66, No. 26, 2001 8891
mixture was poured onto ice, and the resulting precipitate was
collected by filtration to give the crude product as a yellow-
orange solid, which was purified by sublimation (130 °C, 0.008
mmHg) (0.15 g, 0.7 mmol, 33%): mp 164-167 °C; 1H NMR
(DMSO-d6) δ 8.07 (d, 2H, J ) 9.0), 7.48 (d, 2H, J ) 7.5), 6.83
pyridoneimine 4 exists predominantly in the zwitterionic
form, whereas phenylpyridoneimine 2 is neutral-quinoid.
(4) The polarity of the media is able to significantly affect
the relative importance of the two limit forms 1-A and
1-B.
1
(d, 2H, J ) 9.0), 6.34 (d, 2H, J ) 7.4), 3.57 (s, 3H); H NMR
In conclusion, we have accessed
a whole range
(CDCl3) δ 8.08 (d, 2H, J ) 9.0), 6.96 (d, 2H, J ) 7.0), 6.94 (d,
2H, J ) 9.0), 6.29 (d, 2H, J ) 7.0), 3.50 (s, 3H). Anal. Calcd.
for C12H11N3O2: C, 62.86; H, 4.85; N, 18.33. Found: C, 63.13;
H, 4.70; N, 18.30.
of push-pull electron structures, from fully aromatic-
zwitterionic to quinoid-neutral forms, going through all
the intermediate situations along the path. Most impor-
tantly, this result was achieved in a relatively small
homogeneous series of compounds, by careful use of
substituent and media effects. We believe that the results
we have shown should be valuable in the search and
investigation of new efficient organic push-pull systems
having optimized π-electron structure dependent ad-
vanced properties.
N-(1-Meth yl-1H-p yr id in -4-yilid en e)-2,4-d in itr oa n ilin e
(4). Powdery potassium carbonate (0.552 g, 4.0 mmol) was
added to a stirred solution of 1-methyl-4-aminopyridinium
triflate (12) (0.775 g, 3.0 mmol) in dry acetone (40 mL). After
the mixture was stirred for 30 min, a solution of fluoro-2,4-
dinitrobenzene (0.558 g, 3.0 mmol) in dry acetone (10 mL) was
added dropwise to the above solution, and the mixture was
stirred for 72 h at room temperature. The solvent was removed
under reduced pressure from the filtered brown reaction
mixture to leave a residue, which was washed wih water (few
mL) and subsequently submitted to chromatography (acetone)
on neutral alumina. Compound 4 was obtained27 as a bright
red solid, which was purified by sublimation (180 °C, 0.005
Exp er im en ta l Section
13C and 15N NMR spectra were recorded using a Bruker
AMX-500 spectrometer operating at 125.70 and 50.75 MHz,
respectively. The spectral parameters and calibrations have
been previously reported.14a 15N chemical shifts are relative
to liquid NH3 (380.23 from nitromethane). Coupling constants
are presented in Hertz. Anhydrous N,N-dimethylformamide
(DMF) was supplied by Fluka and stored over molecular sieves.
Benzene and acetone were dried over Na2SO4 or Drierite for a
few days. Melting points are uncorrected.
1
mmHg) (0.180 g, 0.7 mmol, 23%): mp 208-209 °C; H NMR
(DMSO-d6) δ 8.58 (d, 1H, J ) 2.7), 8.15 (dd, 1H, J ) 9.2, 2.7),
7.72 (d, 2H, J ) 7.5), 7.16 (d, 1H, J ) 9.2), 6.51 (d, 2H, J )
7.5), 3.64 (s, 3H); 1H NMR (CDCl3) δ 8.81 (d, 1H, J ) 2.6),
8.26 (dd, 1H, J ) 9.0, 2.6), 7.18 (d, 1H, J ) 9.0), 7.14 (d, 2H,
J ) 7.6), 6.37 (d, 2H, J ) 7.5), 3.65 (s, 3H); MS (EI) m/e 274
(M+•, 100), 182 (27), 93 (43). Anal. Calcd for C12H10N4O4: C,
52.56; H, 3.68; N, 20.43. Found: C, 52.37; H, 3.70; N, 20.18.
Tr iflu or o-N-(1-m eth yl-1H-p yr id in -4-ylid en e)m eth a n e-
su lfon a m id e (7). Powdery potassium carbonate (1.20 g, 8.7
mmol) was added to a solution of 1-methyl-4-aminopyridinium
triflate (12) (0.900 g, 3.5 mmol) in dry acetone (20 mL). After
the mixture was stirred for 30 min, a solution of trifluoro-
methanesulfonyl chloride (0.59 g, 3.5 mmol) in dry acetone (12
mL) was added dropwise, and the reaction mixture was stirred
for 5 days at room temperature. The solid was filtered off from
the brown mixture while being protected from light, and the
solvent was removed at reduced pressure to leave a residue,
which was taken up with water (5 mL). The resulting solid
was collected by filtration to afford the crude product as a pink
solid (0.27 g, 1.1 mmol, 31%): mp 168-170 °C (EtOH, pink-
yellow solid);1H NMR (DMSO-d6) δ 8.27 (d, 2H, J ) 7.3), 7.27
4-An ilin o-1-m eth ylp yr id in iu m Tr ifla te (11). A solution
of methyl triflate (1.496 g, 9.12 mmol) in dry benzene (3 mL)
was added to a stirred suspension of 4-anilinopyridine16 (1.505
g, 8.84 mmol) in the same solvent (15 mL) at room tempera-
ture. The mixture was stirred overnight and the precipitate
collected to give the practically pure product as a whitish solid
1
(2.896 g, 8.66 mmol, 98%): mp 97-98 °C; H NMR (DMSO-
d6) δ 10.5 (broad, 1H), 8.25 (d, 2H, J ) 7.5), 7.50 (t, 2H, J )
7.9), 7.34-7.29 (m, 3H), 7.11 (d, 2H, J ) 7.5), 3.95 (s, 3H).
Anal. Calcd for C13H13F3N2O3S‚1/2H2O: C, 45.48; H, 4.11; N,
8.16. Found: C, 45.36; H, 3.91; N, 7.86.
N-(1-Meth yl-1H-pyr idin -4-yiliden e)an ilin e (2). 4-Anilino-
1-methylpyridinium triflate (11) (1.004 g, 2.17 mmol) was
treated with 40% aqueous KOH (10 mL) leading to the
separation of a dark yellow oil, which was extracted with
diethyl ether (70 mL). The organic layer was dried and
evaporated to dryness to leave the crude product as a yellow
oil (0.384 g, 1.89 mmol, 87%). A sample was purified by
distillation in a Kugelrohr apparatus (60 °C/0.005 mmHg) to
give a yellow solid: mp 70-72 °C; 1H NMR (DMSO-d6) δ 7.3-
7.1 (m, 4H), 6.86 (t, 1 H, J ) 6.2), 6.71 (d, 2H, J ) 7.0), 6.05
(broad, 1H), 5.94 (broad, 1H), 3.48 (s, 1H); 1H NMR (CDCl3) δ
7.30 (t, 2H, J ) 7.7), 6.97 (t, 1H, J ) 7.3), 6.94-6.89 (m, 3H),
6.76 (d, 2H, J ) 7.4), 6.38 (d, 1H, J ) 8.0), 6.16 (d, 1H, J )
7.4), 3.5 (s, 3H). Anal. Calcd for C12H12N2: C, 78.23; H, 6.56;
N, 15.20. Found: C, 77.72; H, 6.50; N, 14.83.
1
(d, 2H, J ) 7.3), 4.00 (s, 3H); H NMR (acetone-d6) δ 8.22 (d,
2H, J ) 7.3), 7.31 (d, 2H, J ) 7.3), 4.15 (s, 3H). Anal. Calcd
for C7H7F3N2O2S: C, 35.00; H, 2.94; N, 11.66. Found: C, 35.18;
H, 2.83; N, 11.64.
N-(1-Met h yl-1H -p yr id in -4-ylid en e)-p -t olu en esu lfon a -
m id e (8). Meth od A. A solution of N-pyrid-4-yl-p-toluene-
sulfonamide (14) (0.500 g, 2.0 mmol) in anhydrous DMF (8
mL) was added dropwise to a supension of sodium hydride
(0.10 g, 60% oily, 2.5 mmol) in the same solvent (5 mL), under
a nitrogen atmosphere and at a temperature maintained below
25 °C. The reaction mixture was stirred for 30 min at 25 °C,
turning from whitish to pale yellow. A solution of methyl
triflate 0.33 g, 2.0 mmol) in anydrous DMF (2 mL) was then
added dropwise to the ice-cooled mixture. After the mixture
was stirred for 48 h at room temperature, the milky precipitate
was collected, washed with water, and dried over CaCl2 at
reduced pressure to give the practically pure product as a
white solid (0.20 g 0.8 mmol, 40%): mp 238-242 °C (lit.20a
238-239 °C); 1H NMR (DMSO-d6) δ 7.87 (d, 2H, J ) 7.4), 7.64
(d, 2H, J ) 8.2), 7.25 (d, 2H, J ) 8.1), 6.84 (d, 2H, J ) 7.4),
3.74 (s, 3H), 2.35 (s, 3H).
1-Meth yl-4-a m in op yr id in iu m Tr ifla te (12). A solution
of methyl triflate (0.90 g, 5.3 mmol) in dry benzene (4 mL)
was added dropwise to a suspension of 4-aminopyridine (0.50
g, 5.3 mmol) in the same solvent (13 mL) at room temperature.
After the mixture was stirred for 15 h, the resulting solid was
separated by filtration and washed with dry benzene to give
the practically pure product as a white solid (1.23 g, 4.8 mmol,
90%), which was used without further purification in the next
step: mp 109-113 °C; 1H NMR (DMSO-d6) δ 8.08 (d, 2H, J )
7.5), 8.15-7.80 (broad, 2H), 6.78 (d, 2H, J ) 7.5), 3.82 (s, 3H);
Meth od B. Powdery potassium carbonate (0.622 g, 4.5
mmol) was added to a solution of 1-methyl-4-aminopyridinium
13C NMR (DMSO-d6) δ 158.5, 143.7 (2C), 109.3 (2C), 44.4; 15
NMR (DMSO-d6) δ 160 (pyridinium nitrogen).
N
N-(1-Meth yl-1H-p yr id in -4-yilid en e)-4-n itr oa n ilin e (3).
A solution of fluoro-4-nitrobenzene (0.28 g, 2.0 mmol) in DMSO
(7 mL) was added dropwise to a solution of 1-methyl-4-
aminopyridinium triflate (12) (0.52 g, 2.0 mmol) and potassium
tert-butoxide (0.27 g, 2.2 mmol) in the same solvent (13 mL).
After being stirred for 24 h at room temperature, the reddish
(27) A byproduct was separated by column chromatography and
identified as the disubstitution product 13 as a brown solid by 1H
NMR: 1H NMR (DMSO-d6) δ 9.06 (d, 2H, J ) 2.6), 8.74 (dd, 2H, J )
8.9, 2.6), 8.63 (d, 2H, J ) 7.3), 7.96 (d, 2H, J ) 8.9), 7.47 (d, 2H, J )
7.4), 4.12 (s, 3H). No attempts were made to obtain an analytically
purified sample.

8892 J . Org. Chem., Vol. 66, No. 26, 2001
Abbotto et al.
triflate (12) (0.387 g, 1.5 mmol) in dry acetone (10 mL). After
the mixture was stirred for 30 min, a solution of p-toluene-
sulfonyl chloride (0.314 g, 1.6 mmol) in dry acetone (10 mL)
was added dropwise, and the reaction mixture was stirred for
72 h at room temperature. The white precipitate was collected
by filtration, washed with water (a few milliliters), and dried
over CaCl2 at reduced pressure to provide the product (0.240
g, 0.9 mmol, 60%): mp 234-235 °C.
N-[1-(2,4-Din itr op h en yl)-1H-p yr id in -4-ylid en e]-p-tolu -
en esu lfon a m id e (9). A solution of N-pyrid-4-yl-p-toluene-
sulfonamide (14) (0.50 g, 2.0 mmol) in anhydrous DMF (10
mL) was added dropwise to a supension of sodium hydride
(0.10 g, 60% oily, 2.5 mmol) in the same solvent (5 mL), under
a nitrogen atmosphere and at a temperature maintained below
25 °C. After the mixture was stirred for 30 min, a solution of
2,4-dinitrofluorobenzene (0.38 g, 2.0 mmol) in anydrous DMF
(3 mL) was added dropwise. The reaction mixture was stirred
for 5 days at room temperature under nitrogen, poured into a
saturated aqueous solution of sodium chloride (70 mL), and
extracted with ethyl acetate (4 × 70 mL). The combined
organic layers were washed with a saturated aqueous sodium
chloride solution (15 mL), dried, and evaporated to dryness
under reduced pressure to leave a yellowish residue, which
was taken up with diethyl ether to afford the product as a
yellow solid (0.71 g, 1.7 mmol, 85%): mp 245-246 °C; 1H NMR
(acetone-d6) δ 9.08 (d, 1H, J ) 2.6), 8.86 (dd, 1H, J ) 8.7, 2.6),
8.33 (d, 1H, J ) 8.7), 8.01 (d, 2H, J ) 7.8), 7.82 (d, 2H, J )
8.2), 7.34 (d, 2H, J ) 7.9), 7.11 (broad, 2H), 2.41 (s, 3H). Anal.
Calcd for C18H14N4O6S: C, 52.17; H, 3.41; N, 13.52. Found:
C, 52.03; H, 3.51; N, 13.37.
Ack n ow led gm en t. This work was supported in part
by grants from the CNR-Progetto Finalizzato MSTA II
and MURST National Project (Grant 9803191626).
J O015937C