Intramolecular electron transfer in the photochemistry of some nitrophenyldihydropyridines

Article abstract of DOI:10.1021/jo052463z

4-Phenyl-1,4-dihydropyridine-3,5-dicarboxylates contain two π chromophores separated by an sp³ carbon. The lowest singlet is localized on the dihydropyridine moiety (¹PyH₂-Ph) and emits a blue fluorescence (with close to unitary efficiency in glass at 77 K). In 3-nitrophenyl derivatives (PyH₂-PhNO₂, some of which are photolabile drugs) the fluorescence is completely quenched. Reasonably, this is due to intramolecular electron transfer between the close-lying donor and acceptor moieties to give the charge-separated species (PyH₂ ^.+-PhNO₂^.-). In EPA glass at 77 K, back-electron transfer gives the dihydropyridine-localized triplet ( ³PyH₂-PhNO₂), which emits a yellow phosphorescence. In solution, deprotonation from the radical cation on the dihydropyridine moiety initiates rearomatization, finally giving Py-PhNO ₂ with low quantum yield (5 × 10^-4 to 5 × 10^-3, increasing up to 0.013 by irradiation at 254 nm, where direct excitation of the nitrophenyl chromophore contributes). In the presence of triethylamine, the reaction changes to neat reduction of the nitro group. When a tethered alkylamino group is present, oxidative degradation of that moiety occurs, again via an electron-transfer intramolecular process. This has been found with the drug nicardipine, where photodegration is more efficient (Φ 0.02 to 0.1). Donor-acceptor dyads of this type, easily available through the Hantzsch synthesis, may be useful for building new photoinduced electron-transfer systems.

Full text of DOI:10.1021/jo052463z

Intramolecular Electron Transfer in the Photochemistry of Some
Nitrophenyldihydropyridines
Elisa Fasani, Maurizio Fagnoni, Daniele Dondi, and Angelo Albini*
Department of Organic Chemistry, UniVersity of PaVia, V. Taramelli 10, 27100 PaVia, Italy
angelo.albini@unipV.it
ReceiVed NoVember 29, 2005
4-Phenyl-1,4-dihydropyridine-3,5-dicarboxylates contain two π chromophores separated by an sp3 carbon.
The lowest singlet is localized on the dihydropyridine moiety (1PyH2-Ph) and emits a blue fluorescence
(with close to unitary efficiency in glass at 77 K). In 3-nitrophenyl derivatives (PyH2-PhNO2, some of
which are photolabile drugs) the fluorescence is completely quenched. Reasonably, this is due to
intramolecular electron transfer between the close-lying donor and acceptor moieties to give the charge-
separated species (PyH2•+-PhNO2•-). In EPA glass at 77 K, back-electron transfer gives the
dihydropyridine-localized triplet (3PyH2-PhNO2), which emits a yellow phosphorescence. In solution,
deprotonation from the radical cation on the dihydropyridine moiety initiates rearomatization, finally
giving Py-PhNO2 with low quantum yield (5 × 10-4 to 5 × 10-3, increasing up to 0.013 by irradiation
at 254 nm, where direct excitation of the nitrophenyl chromophore contributes). In the presence of
triethylamine, the reaction changes to neat reduction of the nitro group. When a tethered alkylamino
group is present, oxidative degradation of that moiety occurs, again via an electron-transfer intramolecular
process. This has been found with the drug nicardipine, where photodegration is more efficient (Φ 0.02
to 0.1). Donor-acceptor dyads of this type, easily available through the Hantzsch synthesis, may be
useful for building new photoinduced electron-transfer systems.
Dihydropyridines are excellent antioxidants.1 The easily
prepared Hantzsch esters (2,6-dialkyl-3,5-dialkoxycarbonyl-1,4-
dihydropyridines)2 have been used in this role for a variety of
applications, from modeling NADH in biochemistry3 to anti-
knocking agent in fuels4 or to photosensitive polymers.5 Many
of these Hantzsch dihydropyridines bear a (substituted) phenyl
group in position 4 and thus contain two independent π-systems
separate by an sp3 carbon. The flanking ester groups in positions
3 and 5 are expected to keep the phenyl group roughly
perpendicular to the dienaminoester moiety of the dihydropyr-
idine ring, as verified in the crystal structure.6 Noteworthy, the
same, or closely related, molecules are also used in therapy
against cardiac diseases for their activity as calcium channel
blockers7a,b as well as, more recently, for treating pathologies
* Tel: +39 0382 987316. Fax: +39 0382 987323.
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Okazaki, O.; Seto, Y.; MacDonald, T. L. Xenobiotica 1995, 25, 689.
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K.; Hoshiko, T.; Ozaki, S. Synthesis 1983, 761. Kellog, R. M.; van Doren,
H.; Hedstrand, D.; Kooi, J.; Kruizinga, W. H.; Troostwijk, C. B. J. Org.
Chem. 1980, 45, 2854. Vanden Eynde, J. J.; Mayence, A. Molecules 2003,
8, 381. Lavilla, R. J. Chem. Soc., Perkin Trans. 1 2002, 1141.
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1442. Fossheim, R.; Joslyn, A.; Solo, A. J.; Luchowski, E.; Rutlege, A.;
Triggle, D. J. J. Med. Chem. 1988, 31, 300. Wang, S. D.; Herbette, L. G.;
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Trumbore, W.; Mason, P. Am. J. Cardiol. 1999, 84, 16L. (d) Velena, A.;
Zibers, J.; Durbus, G. Cell. Biochem. Funct. 1999, 17, 237. (e) Allanore,
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10.1021/jo052463z CCC: $33.50 © 2006 American Chemical Society
Published on Web 02/02/2006
J. Org. Chem. 2006, 71, 2037-2045
2037

Fasani et al.
for a number of applications,16 (ii) a better knowledge of the
relatively little explored photochemistry of 3-nitrobenzyl deriva-
tives15 would be obtained, and (iii) a rationale for the photo-
lability (and possibly the phototoxicity) of such drugs may be
offered.
SCHEME 1
Results
Photoreactions. The compounds considered in this study
were esters of the 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydro-
pyridine-3,5-dicarboxylic acid. These were the dimethyl ester
1, distinguished from nifedipine only by the position of the nitro
group, the corresponding methyl ethyl ester 2, the drug
nitrendipine, as well as two derivatives containing a functional
group in one of the ester alkyl chains, namely the isopropyl
methoxyethyl ester 3 (nimodipine) and the methyl N-(methyl)-
N-(benzyl)aminoethyl ester 4 (nicardipine). These compounds
exhibit an absorption band in the near UV, with a maximum at
ca. 350 nm (the tail extending in the visible results in a yellow
color) and at ca. 230 nm. They are readily soluble in most
organic solvents, but not in water, and most of the experiments
were carried out in methanol and in acetonitrile, two solvents
of differing hydrogen-donating ability. Irradiations were carried
out at two wavelengths, 254 and 366 nm, corresponding to the
two main band systems and under two conditions, air-
equilibrated and argon-flushed solutions.
Irradiation of the dimethyl ester 1 under all of the above
conditions gave a single product, as determined by HPLC
monitoring. This was identified as the corresponding nitrophen-
ylpyridine 5 by comparison with an authentic sample (Table 1,
Scheme 2). At 50% conversion of 1, product 5 was in every
case ca. 70% of the consumed dihydropyridine. Likewise, both
the methyl ethyl ester 2 and the methyl methoxyethyl ester 3
gave the nitro derivatives 6 and, respectively, 7. With 3, HPLC/
MS analysis showed a minor peak by irradiation at 254 nm in
Ar-flushed MeCN or MeOH, but not under different conditions,
with MW corresponding to the nitroso analogue of compound
7 (8), which was not further investigated in view of the small
amount.
such as ischemia, arteriosclerosis, and stroke for their antioxidant
activity.7c-f Most of these drugs bear a nitro group on the phenyl
ring and thus contain both an easily oxidized and an easily
reduced moiety in the same molecule, a fact that may have a
bearing on their biological activity.8a,b
The donor-acceptor structure8c raises the question of whether
an intramolecular redox reaction may occur, a step that may be
easier under photochemical conditions. Actually, some drugs
of this family are known to be photolabile and must be protected
from light-exposure. The 2-nitrophenyl derivative nifedipine has
been in use for a long time as a coronary vasodilator and is
strongly photoreactive. This has motivated a series of photo-
chemical and photobiologic studies showing that this compound
is converted into the corresponding 2-nitrosophenylpyridine
(Scheme 1),9 a reaction that can be classed among the well-
known intramolecular redox process of 2-nitrobenzyl deriva-
tives,10 and occurs both in solution and in the solid state.
Whether a significant photodecomposition takes place in the
skin after intake of the drug and a toxic effect results is a debated
subject.11
2-Nitrophenyl derivatives are ill suited for the study of
photoinduced electron-transfer processes because of the fast
chemical reaction occurring. Better models can be found among
the “second generation”12 cardiac drugs, some of which contains
the 3-nitrophenyl, rather than the 2-nitrophenyl, moiety. These
have been found to be again photolabile, though at a lower
degree,13 but the available literature is mainly limited to the
determination of the degradation kinetics in drug preparations.14
It appeared to us that a more extensive study of the photochem-
istry of these molecules was warranted because (i) excitation
may induce intramolecular electron transfer between two
moieties held in a definite position, a topic actively investigated
In the case of the aminoethyl ester 4 the results were different,
in that the corresponding nitrophenyl derivative (9, ca. 40% in
MeCN and 20% in MeOH, both argon and air equilibrated) was
accompanied by two further peaks. Separation by column
chromatography after irradiation in acetonitrile allowed recog-
nizing these as nitrophenyldihydropyridines in which the ester
side was modified. Two products were obtained from chroma-
tography, namely the N-benzyl and the N-benzyl-N-formyl
derivatives (10 and 11, respectively, Scheme 3).
(8) (a) Schleifer, K. J. J. Med. Chem. 1999, 42, 2204. (b) Schleifer, K.
J. Pharmazie 1999, 54, 804. (c) Compare Nelsen, S. F. In Electron Transfer
in Chemistry; Balzani, V., Ed.; Wiley-VCH: Weinheim, 2001; Vol. 1, p
342.
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Thoma, K.; Kerker, R. Pharm. Ind. 1992, 54, 465. (c) Shim, S. C.; Pae, A.
N.; Lee, Y. J. Bull. Korean Chem. Soc. 1988, 9, 271. (d) Pietta, P.; Rava,
A.; Biondi, P. J. Chromatog. 1981, 210, 516. (d) Stasko, A.; Brazova, V.;
Biskupic, S.; Ondrias, K.; Misik, V. Free Rad. Biol. Med. 1994, 17, 545.
(e) de Vries, H.; Beijersbergen van Henegouwen, G. M. J. Photochem.
Photobiol. B: Biol. 1998, 43, 217. (f) Buttafava, A.; Faucitano, A.; Fasani,
E.; Albini, A. Res. Chem. Intermed. 2002, 28, 231. (g) Fasani, E.; Dondi,
D.; Ricci, A.; Albini, A. Photochem. Photobiol. 2006, 82, in press.
(10) Barltrop, J. A.; Plant, P. J. J. Chem. Soc., Chem. Commun. 1966,
827. Nurmukhametov, R. N.; Sergeev, A. M. Zh. Fiz. Khim. 1990, 64, 308.
Walker, J. W.; Reid, G. P.; McCray, J. A.; Trentham, D. R. J. Am. Chem.
Soc. 1988, 110, 7170.
(11) Al-Ajimi, H. S.; Dawe, R. S.; Renwick, A. G.; Macklin, B. S.;
Ferguson, J.; Gibbs, N. K. Photoderm. Photoim. Photomed. 2000, 16, 111.
Fujii, H.; Berliner, L. J. Magn. Reson. Med. 1999, 42, 691.
(12) Freedman, D. D.; Waters, D. D. Drugs 1987, 34, 578.
(13) Mei, Q.; Shang, P.; Zhao, D.; Zhou, G. Zhongguo Yaoxue Zazhi
1998, 33, 291.
(15) See, e.g.: Muralidharan, S.; Beveridge, K. A.; Wan, P. J. Chem.
Soc., Chem. Commun. 1989, 1426.
(16) Wegenwijs, B.; Verhoeven, J. W. AdV. Chem. Phys. 1999, 106, 221.
Timberlake, L. D.; Morrison, H. J. Am. Chem. Soc. 1999, 121, 3618. Liu,
G.; Heisler, L.; Li, L.; Steinmetz, M. G. J. Am. Chem. Soc. 1996, 118,
11412. Osuka, A.; Noya, G.; Taniguchi, S.; Okada, T.; Nishimura, Y.;
Yamazaki, I.; Mataga, N. Chem. Eur. J. 2000, 6, 33. Maruyama, K.; Osuka,
A.; Mataga, N. Pure Appl. Chem. 1994, 66, 867. Kaplan, R. W.; Napper,
A. M.; Waldeck, D. H.; Zimmt, M. B. J. Am. Chem. Soc. 2000, 122, 12039.
Zhang, L. P.; Chen, B.; Wu, L. Z.; Tung, C. H.; Cao, H.; Tanimoto, Y.
Chem. Eur. J. 2003, 9, 2763. Guo, X.; Zhang, D.; Zhang, H.; Fan, Q.; Xu,
W.; Ai, X.; Fan, L.; Zhu, D. Tetrahedron Lett. 2003, 59, 4843. Miranda,
M. A.; Lahoz, A.; Bosca, F.; Metni, M. R.; Abdelouahab, F. B.; Castell, J.
V.; Perez-Prieto, J. Chem. Commun. 2000, 2257. Le, T. P.; Rogers, J. E.;
Kelly, L. A. J. Phys. Chem A 2000, 104, 6778. Levy, S. T.; Rubin, M. B.;
Speiser, S. J. Am. Chem. Soc. 1992, 114, 10747. Pincock, J. A.; Rifai, S.;
Stefanova, R. Can. J. Chem. 2001, 79, 63. Wagner, P. J.; El-Taliawi, G.
M. J. Am. Chem. Soc. 1992, 117, 8325.
(14) Mielcarek, J. Acta Pol. Pharm. 1995, 52, 59. Mielcarek, J. Acta
Pol. Pharm. 1995, 52, 465. Jakobsen, P.; Mikkelsen, E.; Laursen, J.; Jensen,
F. J. Chromatograph. 1986, 374, 383. Mielcarek, J. Pharmazie 1996, 51,
477.
2038 J. Org. Chem., Vol. 71, No. 5, 2006

Photochemistry of Some Nitrophenyldihydropyridines
TABLE 1. Quantum Yield of Reaction and Products Formed in the Photolysis of dihydropyrines 1-4a
compd
conditions
Φr(Ar), products (%)
0.013, 5b
0.004, 5
0.003, 5
0.0006, 5
0.003, 5 (5), 12 (40), 13 (18), 14 (12)
0.013, 6
0.005, 6
0.004, 6
Φr(air), products (%)
0.013, 5
0.004, 5
0.003, 5
0.0005, 5
1
MeOH, 254 nm
MeOH, 366
MeCN, 254
MeCN, 366
MeCN, 366c
MeOH, 254
MeOH, 366
MeCN, 254
MeCN, 366
MeOH, 254
MeOH, 366
MeCN, 254
MeCN, 366
MeCN, 366c
EtOH, 366f
MeOH, 254
MeOH, 366
MeCN, 254
MeCN, 366
2
3
0.014, 6
0.005, 6
0.003, 6
0.0005, 6
0.022, 7
0.004, 7
0.003, 5
0.0005, 7
0.0004, 6
0.021, 7(70)d
0.004, 7
0.004, 7 (50)d
0.0006, 7
0.004, 7e
e0.0005
4
0.064, 9 (7), 10 (21), 11 (20)
0.018, 9 (16), 10 (18), 11 (21)
0.097, 9 (36), 10 (20), 11 (7)
0.027, 9(43), 10 (17), 11 (8)
0.048, 9 (12), 10 (20), 11 (21)
0.021, 9 (19), 10 (22), 11 (20)
0.083, 9 (37), 10 (18), 11 (7)
0.022, 9 (40), 10 (18), 11 (8)
a Quantum yields determined by HPLC at 15-25% conversion. Products distribution at ca. 50% conversion. b When not indicated, the product amounts
to ca. 70% of the converted starting compound. c In the presence of 0.1 M triethylamine. d Product 7 was accompanied by a small amount of the nitroso
analogue 8, as indicated by HPLC analysis. e Product 7 was accompanied by the amino-, hydroxylamino-, and nitrosophenyl-1,4-dihydropyridines analoguous
to products 12-14, as indicated by HPLC/MS analysis. f In an EtOH glass at 77 K.
SCHEME 2
SCHEME 4
Furthermore, irradiation in the matrix was carried out in the
case of 4. A solution in ethanol was degassed and brought to
90 K. Under these conditions, the absorption spectrum showed
some changes, in that the bands around 360 and 280 nm acquired
some structure and were red-shifted by ca. 10 nm. Prolonged
irradiation at 366 nm under these conditions produced no
change, demonstrating that Φr e 0.0005.
SCHEME 3
In view of the low quantum yield of reaction of these
dihydropyridines, it was deemed useful to determine whether
the reaction might be more effective in the presence of a suitable
additive. Positive results were obtained with triethylamine, and
the conversion of both 1 and 3 was considerably faster when
the amine was present at >0.01 M concentration. The product
distribution was also changed, with the respective nitrophen-
ylpyridines 5 and 7 now accompanied by some faster eluting
products, one of which predominating. The result was more
closely examined with 1, where comparison with authentic
standards showed that the main product at complete consump-
tion of the starting compound was the aminophenyldihydro-
pyridine 12 and the minor ones the corresponding nitroso and
hydroxylamino derivatives 13 and 14 (Scheme 4).
Photophysical Data. Dihydropyridines 1-4 exhibited no
detectable fluorescence at room temperature. They showed an
intense yellow phosphorescence (but only a very weak fluo-
rescence) in the matrix (EPA glass at 77 K) as reported in Table
2. As a representative example, the emission of 1 under these
conditions is reported in Figure 1a. Addition of 10% triethyl-
amine did not alter the emission.
Separate experiments at 15-25% conversion of the starting
material were carried out for the determination of the quantum
yields of reaction (Φr) under the above conditions. The results
are reported in Table 1.
J. Org. Chem, Vol. 71, No. 5, 2006 2039

Fasani et al.
FIGURE 1. (a) Fluorescence (×10) and phosphorescence of compound 1 in EPA glass at 77 K. (b) Fluorescence and phosphorescence (×50) of
compound 16 in EPA glass at 77 K.
TABLE 2. Data on the Luminescence from Dihydropridines 1-4,
15, and 16
fluorescence
295Ka
phosphorescence
77Kb
77Kb
ET,
compd
λ
max, nm
Φf
Φf
λ
max, nm
Φp
kcal mol-1
15
16
1
2
3
437 (5850)a 0.006 0.8
c
439 (5790)a 0.005 0.8 516, 548 <1 × 10-3
60.2
60.3
60.3
60.3
59.6
c
c
c
c
513, 547
514, 545
514, 545
514, 547
0.12
0.11
0.10
0.10
4
a In acetonitrile; similar values in methanol; the Stoke’s shift (cm-1) is
indicated in parentheses. b In EPA glass. c Not detected.
It appeared important to understand the role of the nitrophenyl
moiety in determining the observed luminescence. Therefore
we examined some analogues lacking this group, viz. the
corresponding 2, 4, 6-trimethyl (15) and 2, 6-dimethyl-4-
phenyldihydropyridines (16). As previously reported for related
derivatives,17 these exhibited a blue fluorescence (see Figure
1). This was rather weak in fluid solution (Φf = 5 × 10-3, τf
0.3 ns for 15, 0.15 ns for 16). However, the emission became
much more intense (Φf 0.8) and somewhat structured in EPA
glass at 77K, while the lifetime became much longer (τf 8 ns,
kf 1.2 × 108 s-1 for both compounds).
FIGURE 2. Fluorescence of compounds 15 (upper trace) and 16 in
acetonitrile at 300K.
The yellow phosphorescence characteristic of compounds
1-4 was barely detected for 16 (see Figure 2) and not at all for
15. A sensitization experiment was attempted. Thus, a glass
containing both naphthalene and 15, under conditions in which
most of the light was absorbed by the former, exhibited a
phosphorescence spectrum resulting form the sum of the
naphthalene phosphorescence and of a further weak emission.
The latter had the same shape as that from the above phenyl
derivatives (see Figure 3).
FIGURE 3. Phosphorescence from a mixed solution of naphthalene
and compound 15 in EPA glass at 77 K (upper trace) and the spectrum
resulting from subtraction of the naphthalene phosphorescence emission
from the above curve (lower trace). The inset shows the decay of the
415 nm transient absorption resulting from flashing (266 nm) a
naphthalene solution in acetonitrile (upper trace) as well as of an
identical solution containing 2.3 × 10-3 M 15 (lower trace).
Nanosecond flash photolysis in acetonitrile solution evidenced
no transient in the region 380-650 nm for any of the
dihydropyridine considered above. However, flashing a naph-
thalene-15 mixed solution in MeCN (under conditions where
the former absorbed most of the light) showed that the
naphthalene triplet was efficiently quenched by the dihydro-
(17) Deme, A. K.; Lusis, V. K.; Dubur, G. Y. Khim. Geterotsikl. Soedin.
1987, 67.
2040 J. Org. Chem., Vol. 71, No. 5, 2006

Photochemistry of Some Nitrophenyldihydropyridines
expect from its push-pull structure (an enamino ester), the
emission is characterized by a strong Stoke’s shift (>5000 cm-1
in acetonitrile and methanol). The fluorescence is weak at room
temperature, with a quantum yield lower than 0.0119 and a short
lifetime (kf > 3 × 109 s-1). However, this is intense in EPA at
77 K where Φf approaches the unitary value and the observed
rate constant, kf ∼ 1 × 108 s-1, corresponds to that expected
for S1 on the basis of the absorption spectrum (for the long-
wavelength band. It has been calculated that f = 0.120 and the
“natural” rate constant kf = 1 × 108 s-1). Such a large
temperature dependence of the fluorescence is reasonably due
to the non rigid framework of the bis-enaminoester chromophore
(see above and Figure 4). Equilibration between different
conformers is fast (see the Supporting Information) and this
introduces an efficient channel for non radiative decay. As a
result, the experimental fluorescence lifetime at room temper-
ature is dictated by internal conversion (i.e., kd ∼ 5 × 109 s-1
)
1
in solution, while this mode is blocked in a rigid glass.
FIGURE 4. Optimized (B3LYP 6-31+G(d)) molecular structure of
compound 1.
Introduction of the phenyl group in position 4 as the second
chromophore is not expected to involve a major π interaction
with the dihydropyridine moiety, in view of the large angle they
form.6 Indeed, as already remarked by Kurfu¨rst,20 the absorption
spectrum of 4-phenyl derivative 16 (PyH2-Ph) roughly corre-
sponds to the sum of the spectrum of 15 and of that of benzene.
Compound 16 exhibits the same temperature-dependent fluo-
rescence as 15 with an identical shape of the spectrum (see
Figure 2 and Table 2). Thus, with 16 the lowest excited singlet
remains localized on the dihydropyridine moiety, as one would
expect. The almost unitary value of Φf at 77 K indicates that
this state undergoes very little (though non zero, since a weak
phosphorescence can be appreciated, see Figure 1b) intersystem
pyridine (observed rate constant, 3.9 × 109 M-1
s
-1, see the
inset in Figure 3).
Structure. To further document the behavior of these
compounds, the conformations of the nitrophenyl derivative 1
were examined by the B3LYP method. The most stable
conformer (in MeCN bulk) had a flattened boat structure (N
and C4 both over the plane, with torsion angles of 6 and 22°,
see Figure 4). The esters groups were essentially coplanar with
the ring double bonds; the phenyl group formed a 62° angle
with the dihydropyridine ring and had the substitent syn-
antiperiplanar to the C4 hydrogen.18 The most characteristic
feature, however, was that several other conformers were located
with an energy within 1 kcal mol-1 from the above structure.
These differed for the syn or anti position of the 3′-nitrophenyl
group and the orientation of the ester groups. One of the
conformers corresponded to that present in the crystal state (see
the Supporting Information). Thus, it was expected that easy
equilibration occurred in solution and in fact NMR studies had
ascertained that different conformers of 1 were present in
solution.18e
crossing in matrix, kisc/kf e 1 × 10-3 21
. The shape and position
of phosphorescence exclude that it can be attributed to the
nitrobenzene moiety and its similarity to that of fluorescence
supports that it arises from a dihydropyridine localized triplet.
The energy of this state is 60.2 kcal mol-1. The fact that some
phosphorescence is observed despite the inefficient ISC suggests
3
that in glass emission is a major decay path from PyH2-Ph,
just as it occurs from the corresponding singlet in a matrix.
Intersystem crossing is even less significant with 4-methyl
derivative 15, where no spontaneous phosphorescence is
observed. However, the triplet must have a similar energy, as
indicated by the fact that it can be reached through sensitization
by naphthalene, ET 60.5 kcal mol-1. This is supported by
quenching of the naphthalene triplet in solution (see Figure 3,
inset) and observation of sensitized phosphorescence from 15
in the glass in the presence of naphthalene (absorbing >90%
of the exciting light, see Figure 3).
In the 4-(3-nitrophenyl) derivatives 1-4 (PyH2-PhNO2) the
phenyl ring remains askew (see Figure 4) and has no effect on
the dihydropyridine localized S1 state, as indicated by the close
similarity of the long-wavelength part of the absorption spectrum
to that of 15 and 16. The fact that these compounds are virtually
nonfluorescent, either at 295 or at 77 K (Φf in glass e 1 ×
10-2), indicates that a new decay channel is involved. This can
be reasonably proposed to be electron transfer from the
dihydropyridine chromophore (Eox +0.67 V vs Ag/AgNO3 for
Discussion
Excited States Involved. Nitrophenyldihydropyridines 1-4
contain two independent chromophores, the 1,4-dihydropridine-
3,5-dicarboxylate, and the 3-nitrotoluene moieties, separated by
a sp3 carbon and will be indicated by the acronym PyH2-PhNO2
in the following. It is clear that the lowest singlet is localized
on the dihydropyridine moiety. In fact, the long wavelength part
of the absorption spectrum of 1-4 is quite similar to that of
4-unsubstituted and 4-alkyl-substituted analogues such as 15
(PyH2-Me), where only this chromophore is present. The bands
of 15 peak at ca. 350 nm (log ꢀ ∼ 4), 250 (4.2), and 230 nm
(4.35). This compound fluoresces in solution, and as one may
(18) (a) For a previous semiempirical MO conformational analysis, see
ref 18b. For the molecular structure in the crystal state and in solution, see
ref 18c-e. (b) Cotta-Ramusino, M.; Var`ı, M. R. THEOCHEM 1999, 492,
257. (c) Fossheim, R.; Svarteng, K.; Mostad, A.; Rømming, C.; Shefter,
E.; Triggle, D. J. J. Med. Chem. 1982, 25, 126. (d) Rovnyak, G.; Andersen,
N.; Gougoutas, J.; Hedberg, A.; Kimball, S. D.; Malley, M.; Moreland, S.;
Porubcan, M.; Pudzianowski, A. J. Med. Chem. 1988, 31, 936. (e)
Marubayashi, N.; Ogawa, T.; Hamasaki, T.; Hirayama, N. J. Chem. Soc.,
Perkin Trans. 2 1997, 1309.
(19) A previous study reported a much higher Φf value; however, see
ref 17.
(20) Kurfu¨rst, A.; Kuthan, J. Collect. Czech. Chem. Commun. 1983, 43,
1422.
(21) ISC must be even less significant at room temperature, where
nonradiative decay cuts down the singlet lifetime.
J. Org. Chem, Vol. 71, No. 5, 2006 2041

Fasani et al.
biradical D•+-A•-. This condition does not apply to the present
SCHEME 5
case, since the energy of the emitting state is 60.2 kcal mol-1
,
•-
that is 13.3 kcal mol-1 above the PyH2•+-PhNO2 state in
solution.26
However, in a frozen glass the zwitterion is less stabilized,
due to difficult solvent reorganization and probably also of the
hindering of the required intramolecular reorganization. Back-
electron transfer to give a dihydropyridine localized triplet
(3PyH2-PhNO2, see Scheme 5) may thus be possible in glass,
in analogy to what previously observed for other donor-
acceptor dyads.25 Importantly for this issue, Verhoeven and
Paddon-Row showed that with some aniline-cyanonaphthalene
dyads the CT fluorescence shifts to the blue in a frozen MTHF
matrix, with an energy increase by as much as 17 kcal mol-1 26c
.
Photoreactions. As it appears from Table 1, 4-(3-nitrophen-
yl)-1,4-dihydropyridines 1-3 react sluggishly (Φr 0.0005 to
0.02, compare with the 0.4 value observed for the 2-nitrophenyl
analogues;9c,g see below for the more efficient reaction of 4)
and the isolated products (Scheme 2) result from a net oxidation
involving aromatization of the dihydropyridine moiety, rather
than disproportionation with reduction of the nitro group as with
the 2-nitro isomer (Scheme 1). As shown in Table 1, compounds
1-3 react more efficiently at 254 than at 366 nm (by a factor
of 3 to 10) and in methanol rather than in acetonitrile (again by
a factor of 3 to 10); oxygen has a minimal effect. In the previous
section, it was concluded that the relaxed zwitterionic biradical
15, +0.84 for 1 in acetonitrile)22 to the nitrotoluene moiety (Ered
-1.25 V, see Scheme 5). Taking into account the excitation
1
energy, these values show that ET from PyH2-PhNO2 (ES 73
•-
kcal mol-1) to PyH2•+-PhNO2 is largely exothermic.23 The
lack of fluorescence indicates that singlet deactivation through
this channel is fast, ket g 1 × 1010 s-1
.
On the other hand, compounds 1-4 phophoresce in glass at
77 K, and the emission has the same shape as the weak
phosphorescence of 16 but is more intense by 2 orders of
magnitude (Φp ≈ 0.1). The similarity of the vibrational structure
to that of fluorescence supports that the emitting triplet is in
any case localized on the dihydropyridine chromophore (while
the nitrobenzene triplet is higher in energy24 than the emitting
state observed and is not expected to phosphoresce efficiently).
The low Φp in compounds 15 and 16 proves that ISC between
PyH2-localized states (kisc in Scheme 5) is inefficient, and thus,
population of the 3PyH2-PhNO2 state in compounds 1-4 must
involve an interaction with the nitrophenyl moiety (see Scheme
5). Indeed, back-electron transfer to give a localized triplet from
the charge-separated state has been demonstrated in other
tethered donor-acceptor dyads (D-A).25 This requires that (one
of) the localized triplets has a lower energy than the zwitterionic
•-
PyH2•+-PhNO2 is formed in solution.
Deprotonation of the radical cation of Hantzsch esters from
the C4 position is a favored process (path a, Scheme 6, the BDE
is only 4.5 kcal M-1 as calculated through a thermochemical
cycle).27 This does not mean that the process is fast, however,
at least when no proton acceptor is present. The difference
between the present compounds and the 2-nitro isomers is that
in the latter case a facile intramolecular proton transfer to the
nitro group occurs9 (indeed, the nitro group is suitably posi-
tionated over the plane of the dihydropyridine moiety). In the
3-nitro derivatives, proton transfer occurs only intermolecularly
to the solvent (more efficiently with more basic methanol than
with MeCN). This inefficient reaction is followed by stepwise
oxidation of the resulting anion to the final products observed
(Scheme 6, bottom).
A further path operates by irradiation at 254 nm, because
the nitrobenzene chromophore (ꢀ254 ≈ 8000 M-1 cm-1) absorbs
about a half of the light flux. As it is general with nitrobenzene
derivatives, ISC is expected to be fast and formation of a nπ*
localized triplet (PyH2-3PhNO2) competes with (exothermic)
electron transfer from PyH2 (path b, Scheme 6). Hydrogen
(22) Lopez-Alarcon, C.; Squella, J. A.; Miranda-Wilson, D.; Nunez-
Vergara, L. J. Electroanal. 2004, 16, 539. Ogle, J.; Baumane, L.; Stradins,
J.; Duburs, G.; Kadish, V.; Gavars, R.; Lusis, V. Khim. Geterotsikl. Soedin.
1985, 1099.
(23) Calculated ∆G° for intramolecular electron transfer from the PyH2
moiety in 11 to the 3-nitrotoluene moiety ∆G° ) E°(D/D•+) - E°(A•-/A)
ET
- Eexc - e2/ꢀa ) -26.1 kcal mol-1
.
(24) For 3-nitrotoluene, ET has been evaluated as >62.8 kcal mol-1
:
Takezaki, M.; Hirota, N.; Terazima, M. J. Phys. Chem. A 1997, 101, 3443.
(25) (a) Gould, I. R.; Boiani, J. A.; Gaillard, E. B.; Goodman, J. L.;
Farid, S. J. Phys. Chem. A 2003, 107, 3515. (b) Wiederrecht, G. P.; Svec,
W. A.; Wasielewski, M. R.; Galili, T.; Levanon, H. J. Am. Chem. Soc.
1999, 121, 7726. (c) Wiederrecht, G. P.; Svec, W. A.; Wasielewski, M. R.;
Galili, T.; Levanon, H. J. Am. Chem. Soc. 2000, 122, 9715. (d) Hasharoni,
K.; Levanon, H.; Greenfield, S. R.; Gosztola, D. J.; Svec, W. A.;
Wasielewski, M. R. J. Am. Chem. Soc. 1996, 118, 10228. (e) Davis, W.
B.; Ratner, M. A.; Wasielwski, M. R. J. Am. Chem. Soc. 2001, 123, 7877.
(f) Carbonera, D.; DiValentin, M.; Corvaja, C.; Agostini, G.; Giacometti,
G.; Liddel, P. A.; Kuciauskas, D.; Moore, A. L.; Moore, T. A.; Gust, D. J.
Am. Chem. Soc. 1998, 120, 4398. (g) Roth, H. D. J. Phys. Chem. A 2003,
107, 3432. (h) Levanon, H.; Galili, T.; Regev, A.; Wiederrecht, G. P.; Svec,
W. A.; Wasielewski, M. R. J. Am. Chem. Soc. 1998, 120, 6366. (i)
Rybtchinski, B.; Sinks, L. E.; Wasielewski, M. R. J. Am. Chem. Soc. 2004,
126, 12268. (j) Lewis, F. D.; Wu, Y.; Hayes, R. T.; Wasielwski, M. R.
Angew. Chem., Int. Ed. 2002, 41, 3485. (k) Weiss, E. A.; Ahrens, M. J.;
Sinks, L. E.; Gusev, A. V.; Ratner, M. A.; Wasielewski, M. R. J. Am. Chem.
Soc. 2004, 126, 5577. (l) Lukas, A. S.; Wasielwski, M. R. Molecular
Switches 2001, 1. (m) Abad, S.; Pischel, U.; Miranda, M. A. Photochem.
Photobiol. Sci. 2005, 4, 69. (n) Shulte, C. K.; Staerk, H.; Weller, A.; Werner,
H. J.; Nickel, B. Z. Phys. Chem. 1976, 101, 371. Steiner, U. E.; Ulrich, T.
Chem. ReV. 1989, 89, 51.
(26) (a) The free energy of the (solvent separated) zwitterionic biradical,
i.e., the free energy difference between the charge-separated state and the
reagent ground state is ∆G°
) E°(D/D•+) - E°(A•-/A) + [(2.6 eV/ꢀ)
SSRIP
- 0.13 eV], see ref 26b. Assuming that solvent stabilization occurs in the
same way as with intermolecular examples, it can be calculated that for
the PyH2•+-PhNO2•- structure arising from 1, ∆G°SSRIP ) 46.8 kcal mol-1
in acetonitrile. Therefore, the free energy change for intersystem crossing
from the charge separated state to the triplets localized on the dihydropy-
ridine (ET 60.2 kcal mol-1) and on the nitrotoluene (ET > 62.8 kcal mol-1
)
,
moieties in 1 is endoergonic, ∆GE°T ) 13.3 and 15.9 kcal mol-1
respectively. For previous cases of endoergonic formation of a localized
triplet from a charge separated dyad in matrix, see, e.g. refs 25b (∆G°
)
11.9 kcal mol-1) and 26c. (b) Rehm, D.; Weller, A. Isr. J. Chem. 197E0T, 8,
259. (c) Goes, M.; Groot, M.; Koeberg, M.; Verhoeven, J. W.; Lokan, N.
R.; Shepard, M. J.; Paddon-Row, M. N. J. Phys. Chem. A 2002, 106, 2129.
(27) Zhu, X. Q.; Li, H. R.; Li, Q.; Ai, T.; Lu, J. Y.; Yang, Y.; Cheng,
J. P. Chem. Eur. J. 2003, 9, 871. Cheng, J. P.; Lu, Y.; Zhu, X.; Mu, L. J.
Org. Chem. 1998, 63, 6108.
2042 J. Org. Chem., Vol. 71, No. 5, 2006

Photochemistry of Some Nitrophenyldihydropyridines
SCHEME 6
SCHEME 7
fast deprotonation of amine radical cations33 and protonation
of nitrobenzene radical anion,34 suggests that sequential electron
and proton transfer (path c, Scheme 6) may explain the observed
reaction.
abstraction (compare nitrobenzene, Φ>0.01 in i-PrOH)28 gives
radicals Ph-N(O•)OH and Solv•, in turn abstracting hydrogen
from the activated dihyropyridine positions. This finally leads
to nitrophenylpyridines as the main products (ca. 70% yield;
the accompanying reduction reasonably leads tosnondetecteds
anilinodihydropyridines, see Scheme 6). Aromatization of related
dihydropyridines has been previously reported both by photo-
sensitization, e.g., with 9-cyanophenanthrene, conjugated ke-
tones, or onium salts,29 and by reaction with radicals, including
C-centered radicals (analogously to those from the solvent
proposed here).30
Both the zwitterion and the localized triplet are expected to
be short-lived (in the nanosecond order), in accord with the
minimal oxygen effect on the above photoreactions (partial
quenching of the triplet is probably compensated for by
formation of active peroxyl radicals).31
Two reactions involving interaction with amines support the
proposed scheme. Thus, irradiation of 1 in the presence of
triethylamine leads to a moderate increase in the quantum yield
of reaction as well as a change in the products formed. The
new products conserve the dihyropyridine moiety intact and
result from the stepwise reduction of the nitro group to nitroso,
hydroxylamino, and amino groups. As indicated above, the
excited singlet is short-lived (,1 ns), and thus the amine rather
reacts with the zwitterion. The oxidation potential of tertiary
amines is more positive than that of PyH2 by a relatively small
amount (ca. 0.1 V for Et3N).32 This fact, coupled with the known
A second evidence is given by the reaction of (N-methyl-N-
benzyl)aminoethyl ester 4, which turns out to be much more
reactive than compoounds 1 to 3 and undergoes oxidative
cleavage of the alkylamino group in the side chain in a
comparable proportion (from 30 to 80%) with oxidation of the
dihydropyridine moiety. There is no difference either in the
absorption spectrum or in the photophysics of this compound,
thus the initial electron transfer between the two π systems
occurs as in the previous cases. However, the flexible tether in
this molecule makes the amino group able to interact with both
chromophores, and as mentioned above, the oxidation potential
of a tertiary amine is close to that of the dihydropyridine. A
reasonable hypothesis is thus that a secondary ET step from
the amino group ensues again, in this case intramolecularly.
The mobility of this moiety allows interaction with the nitro
group and thus intramolecular proton transfer as indicated in
Scheme 7. Consistent with this shuttle mechanism, this reaction
is much more efficient (Φr 0.05 to 0.1) than the sluggish proton
transfer to the medium and the quantum yield is independent
of the solvent nature. However, the difference between the two
irradiation wavelengths remains, since the amine also quenches
the PhNO2 localized triplet state formed at 254 nm, again adding
a further photoreduction path (compare the photoreduction of
nitrobenzene by amines).35 Noteworthy, compound 4 is virtually
photostable when irradiated in glass at 77 K. Again, this well
fits with the about proposal and the importance of conformation
in inducing intramolecular hydrogen transfer.
(28) Do¨pp, D. In Handbook of Organic Photochemistry and Photobi-
ology; Horspool, W. M., Song, P. S., Eds.; CRC, Boca Raton: 1994; p
1019. Hurley, R.; Testa, A. C. J. Am. Chem. Soc. 1966, 88, 4330.
(29) Taraban, M. B.; Kruppa, A. I.; Polyakiv, N. E.; Leshina, T. V.;
Lusis, V.; Muceniece, D.; Duburs, G. J. Photochem. Photobiol. A: Chem.
1993, 73, 151.
(30) Lo´pez-Alarco´n, C.; Navarrete, P.; Camargo, C.; Squella, J. A.;
Nu´n˜ez-Vergara, L. J. Chem. Res. Toxicol. 2003, 16, 208. Nu´n˜ez-Vergara,
L. J.; Lo´pez-Alarco´n, C.; Navarrete-Encina, P. A.; Atria, A.; Camargo, C.;
Squella, J. A. Free Radical Res. 2003, 37, 109.
(31) Valenzuela, V.; Santander, P.; Camargo, C.; Squella, J. A.; Lo´pez-
Alarco´n, C.; Nu´n˜ez-Vergara, L. J. Free Radical Res. 2004, 38, 715.
(32) Yasui, S.; Tsujimoto, M.; Itoh, K.; Ohno, A. J. Org. Chem. 2000,
65, 4715.
(33) Dombrowski, G. W.; Dinnocenzo, J. P.; Zielinski, P. A.; Farid, S.;
Wosinska, Z. M.; Gould, I. R. J. Org. Chem. 2005, 70, 3791.
(34) Metcalfe, R. A.; Waters, W. A. J. Chem. Soc. B 1969, 918.
(35) Sundararajan, K.; Ramakrishnan, V.; Kuriacose, J. C. Ind. J. Chem.
1983, 22B, 257. Sundararajan, K.; Ramakrishnan, V.; Kuriacose, J. C. Ind.
J. Chem. 1984, 23B, 1086. Do¨pp, D.; Mu¨ller, D.; Seiler, K. H. Tetrahedron
Lett. 1974, 2137.
J. Org. Chem, Vol. 71, No. 5, 2006 2043

Fasani et al.
according to published procedures. Samples of phenyldihydropyr-
idines 12-14 for comparison with the irradiation products of 1 in
the presence of triethylamine were prepared by reduction of
compound 1 through literature procedures.39 N-Benzyl-2-aminoethyl
methyl 1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylate (11)
showed spectroscopic properties identical to those reported in the
literature.40
Photochemistry. Small-scale experiments were carried out on
2 mL samples of 5 × 10-4 M solutions of the dihydropyridines in
MeCN or MeOH in spectrophotometric couvettes after argon
flushing and addition of triethylamine when appropriate. These were
irradiated by means of 15 W low-pressure mercury arcs (254 nm)
or 15 W phosphor-coated lamps (center of emission 366 nm, mid-
height width 35 nm), and the course of the reaction was monitored
by HPLC by using a C-18 inverse phase column and eluting with
methanol-water mixtures. The light flux was measured by ferri-
oxalate actinometry.
Conclusion
The two separate chromophores contained in 4-(3-nitrophen-
yl)-substituted Hantszch dihydropyridines (PyH2-PhNO2) ex-
hibit an opposite photochemistry. The dihydropyridine chro-
mophore decays radiatively both from the singlet and from the
triplet, whereas the short-lived 3-nitrotoluene moiety does not
emit and abstracts hydrogen inefficiently, mainly decaying by
internal conversion. Both the lowest singlet and the lowest triplet
are localized on the PyH2 chromophore but spontaneous ISC
within this moiety is negligible. On the basis of luminescence
data, it is suggested that short path (6 Å) intramolecular electron
transfer occurs efficiently in this dyad. In solution, the zwitterion
undergoes inefficient deprotonation finally resulting in aroma-
tization of the pyridine ring. In the presence of an amine, or
more efficiently of a tethered amino group, hydrogen transfer
to the nitro group rather occurs. This is revealed by the formation
of aminophenyldihydropyridines in the first case and by the
oxidation of the side-chain in the latter one. In glass a 77 K the
zwitterion is less stabilized and back electron transfer leads the
otherwise inaccessible (and phosphorescing) 3PyH2-PhNO2
state.
In the irradiation of compound 1 in the presence of 0.1 M
triethylamine, the photolyzed solutions were examined by HPLC/
MS and the peaks of products 12-14 were recognized by
comparison with authentic samples prepared as above.
Preparative experiments were carried out on 300 mL portions
of 5 × 10 M-3 solutions of the dihydropyridines in an immersion
well apparatus after argon flushing. These were internally irradiated
by means of a 150 W medium-pressure mercury arc through Pyrex
until a ca. 80% conversion was reached (HPLC). Evaporation of
the solvent and chromatography afforded the photoproducts reported
in Table 1, which were recognized by comparison of their
properties, in particular HPLC (RP-18 endcapped column, MeOH/
H2O 7/3 mixture as eluant) and NMR, with authentic samples
prepared as above. In the case of nimodipine (3), a minor peak
with tR 24.0 min and m/z 400, as expected for the corresponding
nitrosophenylpyridine 8, was detected but not further investigated.
In the case of nicardipine 4, products 10 and 1140 were formed,
besides aromatized 9.
This solution mechanism rationalizes the photolability of
3-nitrophenyl substituted dihydropyridine cardiac drugs and the
intervention of radicals in it suggests that these drugs may have
a phototoxic effect. Likewise, the radical path offers an
explanation for the use of related molecules for cross-linking
photosensitive polymers.
The photophysics of these molecules is of interest because
of the short-path electron transfer between the two π systems
in a known configuration. This may be taken as a model for
the photochemical events in intermolecular exciplexes. It is
reasonable to expect that changing the reduction potential of
the aryl group in 4 it is possible to modulate the extent of charge
transfer in aryldihyropyridines, conspicuously revealed by the
disappearance of the blue florescence and the appearance of a
yellow phosphorescence when an electron accepting group opens
a path for ISC. Moreover, the results with the methylaminoethyl
ester 4 support that the chemistry can be varied through a further
intramolecular mediation. Thus, the present PyH2-PhNO2 dyads
may be further developed into more complex structures for
predetermined electron transfer, in view of the interest for this
topic (e.g., for modeling photosynthesis,25h,i studying DNA-
mediated electron transfer,25j and building molecular wires25k
or molecular switches).25l The easy synthesis and large pos-
sibility variation of each molecular feature in Hantzsch esters
(aromatic substituent in 4, ester alkyl chain, introduction of
further groups, synthesis of oligomeric structures) suggest that
this class of molecules could be explored for building a range
of simple, metal-free, systems where electron transport occurs
and may find applications. Work toward this target is underway.
N-Benzyl-N-formyl-2-aminoethyl methyl 1,4-dihydro-2,6-
dimethylpyridine-3,5-dicarboxylate (11): whitish powder; mp
1
84-85 °C; H NMR (CDCl3, 50 °C, some of the peaks are split
due to hindered rotations; when this occurs the more intense one
is indicated) δ 2.4 (s, 3H), 2.45 (s, 3H), 3.4 and 3.5 (two m, 2H),
3.7 (s, 3H), 4.2 (m, 2H), 4.3 and 4.5 (AB, 2H), 5.1 (s, 1H), 6.2 (s,
1H), 7.3 (m, 5H), 7.7 (d, 1H), 8.0 (m, 1H), 8.1 (m, 2H), 8.25 (s,
1H); 13C NMR (CDCl3) δ 19.3 (CH3), 19.6 (CH3), 39.3 (CH3), 44.9
(CH2), 50.7 (CH), 51.1 (CH2), 59.8 (CH2), 120.1 (CH), 120.5 (CH),
122.7 (CH), 123.5 (CH), 126.5 (CH), 126.9 (CH), 127.3 (CH),
127.6, 127.7 (CH), 128.3, 133.7 (CH), 144.4, 145.5, 147.9, 149.2,
162.5 (CH), 166.2, 167.0; IR (neat) ν 3310, 1705, 1550, 1500 cm1.
Anal. Calcd for C26H27N3O7: C, 63.28; H, 5.51; N, 8.51. Found:
C, 63.4; H, 5.7; N, 8.2.
Luminescence. The luminescence was measured either at room
temperature or at 77K by means of a fluorimeter. Quantum yields
of emission were measured taking quinine bisulfate (Φf ) 0.546
at room temperature) or carbazole (in glass, Φp ) 0.24)42 as a
standard. The fluorescence lifetime was measured through the
single-photon counting technique.
Calculations. All calculations were carried out by using the
Gaussian 2003 program package (see the Supporting Information).
All the geometric structures of the reactants and transition states
located were fully optimized both in the gas phase and in acetonitrile
Experimental Section
General Methods. Samples of dihydropyridines 2-4 were
kindly supplied by the firm Lusochimica, Milan. Compound 15
was of commercial origin, and compounds 1 and 16 were prepared
by conventional procedures.36 Samples of nitrophenylpyridines 5,
9,37 6, and 738 for comparison with the photoproducts were prepared
(38) Boecher, R. H.; Guengerich, F. P. J. Med. Chem. 1986, 29, 1596.
(39) Santander-Gimenez, I. P.; Nunez-Vergara, L. J.; Squella, J. A.;
Navarrete-Encina, P. A. Synthesis 2003, 2781. Simonicˇ, I.; Stanovnik, B.
J. Heterocycl. Chem. 1997, 1725. Anana, R. D.; Ng, H.; Howlett, S. E.;
Knaus, E. E. Arch. Pharm. 1997, 330, 53.
(36) Carabateas, P. M.; Brundage, R. P.; Gelotte, K. O.; Gruett, M. D.;
Lorenz, R. R.; Opalka, C. J. J.; Singh, B.; Thielking, W. H.; Williams, G.
L.; Lesher, G. Y. J. Heterocycl. Chem. 1984, 21, 1849.
(37) Shibanuma, T.; Iwanami, M.; Fujimoto, M.; Takanaka, T.; Mura-
bami, M. Chem. Pharm. Bull. 1980, 28, 2609.
(40) Iwanami, M.; Shibamura, T.; Fujimoto, M.; Kawai, R.; Tanazawa,
T.; Takahashi, K.; Murakami, M. Chem. Pharm. Bull. 1979, 27, 1426.
(41) Meyer, H.; Wehinger, E.; Bossert, F.; Scherling, D. Arzneim.
Forsch./Drug Res. 1983, 33, 106.
(42) Bonesi, S. M.; Erra-Balsells, R. J. Luminesc. 2001, 93, 51.
2044 J. Org. Chem., Vol. 71, No. 5, 2006

Photochemistry of Some Nitrophenyldihydropyridines
solution using the hybrid density functional B3LYP with the
6-31+G(d) basis set. The optimization of the stationary points in
the solvent bulk was calculated by using Gaussian 03 with the
method B3LYP-6-31G(d)/CPCM with the standard setting for
acetonitrile (see the Supporting Information).
Dr. I. Manet, Bologna, is thanked for the single-photon counting
measurements.
Supporting Information Available: Optimized molecular
structure of the low energy conformers of compound 1 (B3LYP
6-31+G(d) method, torsion angles and atom coordinates supplied).
This material is available free of charge via the Internet at
http://pubs.acs.org.
Acknowledgment. Financial support of this work by the
Department of Education, Rome, in the frame of the PRIN
program is gratefully acknowledged. The firm Lusochimica,
Milan, is thanked for the gift of samples of compounds 2-4.
JO052463Z
J. Org. Chem, Vol. 71, No. 5, 2006 2045