Photochemistry of Hantzsch 1,4-dihydropyridines and pyridines

Article abstract of DOI:10.1016/j.tet.2008.01.104

The photochemistry of some Hantzsch 4-phenyl-1,4-dihydropyridines bearing a substituent on the phenyl ring (the three isomeric chloro derivatives and the 4′-nitro derivative) has been studied. All of these compounds underwent inefficient aromatization to

Full text of DOI:10.1016/j.tet.2008.01.104

Available online at www.sciencedirect.com
Tetrahedron 64 (2008) 3190e3196
www.elsevier.com/locate/tet
Photochemistry of Hantzsch 1,4-dihydropyridines and pyridines
*
Elisa Fasani , Angelo Albini, Mariella Mella
Department of Organic Chemistry, University of Pavia, v. Taramelli 10, 27100 Pavia, Italy
Received 9 October 2007; received in revised form 8 January 2008; accepted 24 January 2008
Available online 31 January 2008
Abstract
The photochemistry of some Hantzsch 4-phenyl-1,4-dihydropyridines bearing a substituent on the phenyl ring (the three isomeric chloro de-
rivatives and the 40-nitro derivative) has been studied. All of these compounds underwent inefficient aromatization to the corresponding pyridines
(quantum yield <10ꢀ4 at 366 nm, <10ꢀ2 at 254 nm). This process is scarcely affected by molecular oxygen and is initiated by proton transfer
(from C4eH), probably to the solvent, from the excited singlet. In turn, the thus formed pyridines were photoreactive with comparable or higher
efficiency. Thus, the 4-(30-chlorophenyl) and 4-(40-chlorophenyl) Hantzsch pyridines underwent positional rearrangement to form two isomers
each. The reaction occurs via Dewar benzene–prismane path. In the case of the minor isomer a further 1,3-shift take place at the Dewar benzene
level. The 4-(20-chlorophenyl) derivative underwent CeCl bond homolysis, which led to cyclization of the phenyl group onto one of the ester
groups forming a pyrane ring.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Photochemistry; Hantzsch 1,4-dihydropyridines; Aromatization; Pyridines
1. Introduction
have been detected (e.g., the corresponding nitro and azoxy
derivatives) clearly result from further thermal reactions of
the nitroso derivative.4,5 The mechanism of this photoprocess
has been clarified through extensive investigations by a variety
The dihydropyridineepyridium redox reactions have, as it
is well known, a primary role in metabolism with NADþ
and NADPþ coenzymes (see Scheme 1a). The easily prepared
Hantzsch esters (1,4-dihydropyridine-3,5-dicarboxylates)1,22
come close to these characteristics and are used as antioxi-
dants in a variety of applications (see Scheme 1b).2
It may be interesting to evaluate whether a photochemical
path may affect this reaction, particularly since these dihydro-
pyridines absorb strongly in the UVA range. However, the
photoreactivity has been studied only for some 4-phenyl-1,4-
dihydropyridine-3,5-dicarboxylates that are used as cardiac
drugs,3 for which photolability is a serious problem. As a mat-
ter of fact, the photochemistry of these compounds has been
investigated in depth for the highly photolabile 4-(20-nitro-
phenyl) derivatives, such as nifedipine and nisoldipine,4 which
give the corresponding 4-(20-nitrosophenyl)pyridines (Scheme
1c) both in solution and in the solid state. Minor products that
H
H
H
CO2H
CO2H
(a)
Oxidation
N
R
N+
R
H
N
H
H
RO2C
R
CO2R
R
RO2C
CO2R
R
(b)
Oxidation
N
H
R
O2N
(c)
ON
RO2C
H
RO2C
CO2R
CO2R
R
hν
R
N
R
R
N
- H2O
H
* Corresponding author. Fax: þ39 0382 987323.
E-mail address: elisa.fasani@unipv.it (E. Fasani).
Scheme 1. Dihydropyridineepyridine (or pyridinium ion) reactions and photo-
chemistry of a nitrophenyldihydropyridine.
0040-4020/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.01.104

E. Fasani et al. / Tetrahedron 64 (2008) 3190e3196
3191
2.5
2
of techniques, and is not characteristic of the dihydropyridine
per se, but rather is an example of the well known intramolec-
ular hydrogen abstraction by o-nitrobenzyl derivatives.6
In contrast, only sparse work has been carried out on other
Hantzsch dihydropyridines. Among cardiac drugs, it has been
found that some 4-phenyl derivatives bearing a nitro group in
position 30, such as nitrendipine and nicardipine, undergo
a photochemical oxidation to the 4-(30-nitrophenyl)pyridines,
although the process is much less efficient.7 It appeared desir-
able that more phenyldihydropyridines were studied, in order
to obtain more knowledge on the photochemistry of such de-
rivatives, in particular for compounds not containing a nitro
group, in order to ascertain whether this substituent had a
determining effect on the photochemistry.
If the reaction involved aromatization, it was relevant to un-
derstand the photochemistry also of the corresponding pyri-
dines, since the photoreactions of the two derivatives may
occur competitively. Here again the literature is not extensive,
and while the photochemistry of simple pyiridine derivatives is
known8 that of heavily substituted derivatives such as
Hantzsch pyridines has been little investigated.9
1.5
1
0.5
0
200
240
280
320
360
400
440 nm
Figure 1. Absorption spectrum of dihydropyridine 1 (- - -), of the correspond-
ing pyridine 5 (d) and of the compound 4 (.), 5ꢁ10ꢀ5 M in acetonitrile.
latter compound was identical to a sample prepared by a path
known in the literature.10b The proportion of such product in-
creased with conversion, indicating that it resulted from a sec-
ondary photoreaction of 5. This was confirmed by independent
irradiation of a solution of 5 under the same conditions (see
Scheme 2, Table 2).
2. Results
Compound 2 gave three products, again with a conversion
dependent yield. The primary photoproduct was pyridine 7
(30%), which in turn was converted to the two further prod-
ucts. These were in a constant ratio (ca. 2:1), although growing
with time with respect to 7 and were obtained in the same ratio
also by separate irradiation of 7. Chromatography gave a mix-
ture of such products and spectroscopic investigations gave
sufficient elements for recognizing them as isomers of 7. In
particular, NMR experiments fully supported their identifica-
tion as rearranged chlorophenylpyridines and allowed the de-
termination of the structure, mainly on the basis of NOE
effects and HMBC correlation (see Section 5).
The most abundant isomer (13%) has the methyl group in
positions 2 and 3 and the aryl group was not vicinal. Long
range correlations between some of the pyridine carbons and
the methyl or phenyl hydrogens allowed assignment of struc-
ture 8 (see Section 5 for details). The minor isomer (7%) had
the methyl groups in 3 and 4, with no NOE with the aryl group
and HMBC correlations indicating that the two CeCOOMe
groups flanked the methyl groups, thus allowing to recognize
formula 9.
Compound 3 followed a closely similar path, with forma-
tion of pyridine 10 as the primary product and a mixture of
two further pyridines 11 and 12 arising through secondary ir-
radiation (as tested by separated experiments on 10). NMR
spectra revealed that 11 and 12 differed from 8 and 9 only
for the position of the chloro atom in the phenyl ring. As for
the nitrophenyl derivative 4, this was aromatized to pyridine
13, which underwent no further change on the timescale used.
The reaction quantum yields of the dihydropyridines 1e4
were measured in low conversion experiments in MeCN and
MeOH, by irradiation both at 360 and at 254 nm (correspond-
ing to the two main bands in the absorption spectrum), both in
air equilibrated and in argon equilibrated solutions. In no cases
did the presence of air change the observed values by >20%.
Pursuing our interest in the photochemistry of Hantzsch dihy-
dropyridines,4b,7 we decided to extend the examination to
further derivatives, in particular to the three isomeric 4-(chloro-
phenyl) derivatives 1e3 (that are also models of cardiac drugs).
Furthermore, the photodegradation of the 4-(40-nitrophenyl)
derivative 4 was tested, in order to complete the series of the
previously investigated 20- and 30-isomers4,7 and to allow the
comparison between homogeneous 4-(chlorophenyl) and 4-
(nitrophenyl) families of Hantzsch dihydropyridines. Addition-
ally, we also explored the photoreactions of the corresponding
pyridines.
The absorption spectra of dihydropyridines 1e3 were al-
most identical, with a long-wavelength band around 355 nm
(3¼7000 Mꢀ1 cmꢀ1) tailing beyond 400 nm, and a further
band at 235 nm (3¼23,000 Mꢀ1 cmꢀ1). The absorption in the
UVA is due to a pp*, internal charge transfer transition. Com-
pound 4 showed in addition a further band at 282 nm
(3¼11,250 Mꢀ1 cmꢀ1), due to the nitrophenyl group (Fig. 1).
Irradiations were carried out both in MeOH or in MeCN, at
254 and at 366 nm. The result was similar in every case, with
a decrease of both absorption maxima and an increase of new
band at 275e280 nm. Isosbestic points were conserved up to
>70% conversion, indicating that either a single product or
a mixture with constant composition was generated. The quan-
tum yield of decomposition was measured on 2.5ꢁ10ꢀ4 M
solutions and the results are reported in Table 1.
Product studies were carried out on 5ꢁ10ꢀ3 M solutions. In
the case of 1, two main products were isolated and identified
as the corresponding pyridine derivative (5, about 60% of
the starting compound, identified by comparison with the ther-
mal oxidized derivative prepared by using HNO3)10a and a dif-
ferent phenylpyridine of structure 6, where a molecule of HCl
had been lost and a further lactone ring had been formed. The

3192
E. Fasani et al. / Tetrahedron 64 (2008) 3190e3196
Table 1
Quantum yield of reaction for the photolysis of isomeric chloro- and nitro-substituted 4-phenyl-1,4-dihydropyridines in argon equilibrated solutions (2.5ꢁ10ꢀ4 M)
Conditions
Compound
a
b
20-Cl
30-Cl
40-Cl
20-NO2
30-NO2
40-NO2
MeCN, 254 nm
MeOH, 254 nm
MeCN, 366 nm
MeOH, 366 nm
4.5ꢁ10ꢀ3
3.3ꢁ10ꢀ3
5.3ꢁ10ꢀ5
7.1ꢁ10ꢀ5
1.2ꢁ10ꢀ3
7.9ꢁ10ꢀ4
2.5ꢁ10ꢀ5
4.8ꢁ10ꢀ5
7.4ꢁ10ꢀ4
1.2ꢁ10ꢀ3
3.2ꢁ10ꢀ5
4.7ꢁ10ꢀ5
0.24
0.23
0.27
0.35
3ꢁ10ꢀ3
1.3ꢁ10ꢀ2
6ꢁ10ꢀ4
6ꢁ10ꢀ3
2.8ꢁ10ꢀ2
8ꢁ10ꢀ4
7ꢁ10ꢀ3
4ꢁ10ꢀ3
a
From Ref. 4b.
From Ref. 7.
b
Thus, only the data under argon are reported in Table 1, where
the data for the 20- and 30-nitro analogues are also gathered for
the sake of comparison.
The photoreactions could conveniently be followed by UV
spectroscopy, since the absorption spectra of the pyridines 5,
7, 10, and 13 were considerably blue-shifted with respect to
the starting dihydropyridines. The spectra were characterized
by a band (3 ca. 4000 Mꢀ1 cmꢀ1) at ca. 280 nm (see Fig. 1),
which was rather similar to that of simple pyridines.
In all of the other cases, net oxidation of the dihydro deriva-
tives (general formula 14, see Scheme 3) to give the corre-
sponding nitrophenyl or chlorophenyl pyridine takes place,
but the reaction is sluggish. Thus, the quantum yield of reac-
tion is in the order of 10ꢀ5 by irradiation in the long-wave-
length band and reaches 1ꢁ10ꢀ3 at shorter lirr. We find no
difference in the quantum yield in Ar saturated or air equili-
brated solutions, and confirmed the indifference to the pres-
ence of oxygen by experiments carried out after thorough
degassing of the solution by four freezeedegassingethaw cy-
cles to 1ꢁ10ꢀ6 Torr. Apparently, oxygen has no role in the
aromatization of Hantzsch dihydropyridines by direct irradia-
tion. The occurring of aromatization by photosensitized oxy-
genation has been reported for some compounds of this
type,11 but that appears to be a different reaction.
3. Discussion
3.1. Photochemistry of the dihydropyridines
A look at the efficiency of the photoreactions of the 4-(chloro-
phenyl)- and the 4-(nitrophenyl)dihydropyridines shown in Ta-
ble 2 singles out the case of the 4-(20-nitrophenyl) derivative.
This gives the corresponding nitrosophenylpyridine, i.e., an
intramolecular redox process, with remarkable efficiency.4
That the rather weak C4eH bond undergoes homolysis or
heterolysis in the excited state is reasonable in view of the sta-
bilization of the resulting pyridinyl radical (17) and of the ar-
omatic pyridinium cation (18) as well as of the structure of the
Cl
H
O
Cl
CO2Me
MeO2C
Me
CO2Me
hν
MeO2C
Me
MeO2C
Me
O
+
N
H
Me
N
Me
6
N
Me
5
1
hν
Cl
Cl
Cl
N
Cl
H
MeO2C
Me
CO2Me MeO2C
CO2Me
Me
MeO2C
+
MeO2C
CO2Me
Me
N
+
Me
MeO2C
N
H
Me Me
N
hν
Me
Me
7, 3-Cl
10, 4-Cl
8, 3-Cl
9, 3-Cl
2, 3-Cl
3, 4-Cl
11, 4-Cl
12, 4-Cl
hν
NO2
O2N
H
MeOOC
Me
COOMe
Me
MeOOC
Me
COOMe
hν
N
N
Me
13
H
4
Scheme 2. Photoproducts from dihydropyridines 1e4.

E. Fasani et al. / Tetrahedron 64 (2008) 3190e3196
3193
Table 2
Products from the irradiation of 4-(chlorophenyl)-1,4-dihydropyridines 1e3
involves hydrogen transfer, probably to the solvent. In fact,
the product distribution was the same with 2.5ꢁ10ꢀ4 and
5ꢁ10ꢀ3 M dihydropyridine starting concentration, and there
is no indication of a base (dihydropyridine) induced deproto-
nation, not expected also in view of the short excited state life-
time. Taking into account the intensive absorbance of these
compounds in the near UV, this phenomenon may occur also
with ambient light and may be important in the photodegrada-
tion (and phototoxicity) of drugs of dihydropyridine structure.
Starting compound
Products (% yield)
1, 20-ClC6H4e
2, 30-ClC6H4e
3, 40-ClC6H4e
5 (60%), 6 (15%)
7 (30%), 8 (13%), 9 (7%)
10 (50%), 11 (10%), 12 (5%)
excited state. In fact, the strong absorptivity of the S0/S1
transition supports the internal electron transfer character of
the corresponding excited state. As a result, this has some
zwitterionic character,12 with a partial positive charge on the
enamine moiety (14*h15, see Scheme 3). Analogy can be
drawn with the known chemistry of the 1,4-dihydropyridine
radical cation, for which a heterolytic multi-step mechanism
initiated by transfer of a proton from position 4 followed by
one-electron loss has received computational support.13 This
suggests that in the present case ionization and deprotonation
is a viable process.14
This fits with the increased efficiency observed at shorter
lirr, since in that case the excited state is formed with a surplus
vibrational energy that facilitates the cleavage. A further indi-
cation is given by the fact that the 20-chlorophenyl derivative is
somewhat more reactive than its isomers, although, differently
from the case of the nitro analogues, no intramolecular H
transfer path is available here. Reasonably, the increase is
rather related to the larger stabilization gain in 20-substituted
derivatives when loss of the hydrogen in 4 relieves crowding
at that position.
Furthermore, a nitro group in 30 or 40 (when this is in 20
a different mechanism comes in, as mentioned above) en-
hances the yield of aromatization because the nitrophenyl
group participates to the delocalization of the negative charge,
thus increasing the zwitterionic character of the excited state,
and again facilitates ionization and deprotonation.
As for the multiplicity of the excited state involved, the lack
of oxygen effect supports that the reactive state is short-lived.
This is reasonably the singlet, since photophysical studies in-
dicated that dihydropyridines of this type undergo negligible
ISC.7,15 Thus, the aromatization of dihydropyridines is ob-
tained upon direct irradiation, although with a low yield, and
3.2. Photochemistry of the pyridines
At any rate, the rearomatization path remains inefficient
and secondary photoreactions of the pyridines become com-
petitive with the primary process. The UV spectrum of these
derivatives is characterized by an intense absorption around
280 nm as the long-wavelength band. Apart from a red shift
of some 15 nm, this band is quite similar to that of parent
pyridine. In the case of simple pyridines it has been discussed
whether this means that the lowest singlet state of pyridine is
pp* or there is a hidden, weak transition and the first singlet
excited state is np*. Actually different calculation methods
give different results.7 With the present compounds there is
no indication of hydrogen abstraction that may indicate the
role of the latter state, probably because this is shifted to
higher energy by electron-withdrawing ester groups, and the
three isomeric 4-chlorophenyl derivatives undergo two differ-
ent reactions, one in the case of 5 and one in the case of 7
and 10.
The conversion of 5 to 6 is related to the photodechlorina-
tion observed with chlorobiphenyls and reasonably implies ho-
molytic cleavage of the CeCl bond. The fact that this process
has been detected only with the 20-chlorophenyl derivative 5
suggests however that some specific interaction is involved
in this case. Actually, the CeCl bond projects over the ring
p orbitals, a fact that may facilitate the cleavage due to the for-
mation of a chloro atomebenzene p complex that involves
a significant stabilization.16 Easy intramolecular attack onto
the ester function finally leads to formation of the observed
lactone (Scheme 4). A far analogy for this process may be
Ar
δ-
δ-
*
Ar
Ar
H
O
O
H
MeO2C
Me
CO2Me
Me
MeO2C
Me
CO2Me
MeO
Me
OMe
Me
15
N
+
N
Me
N
H
H
-
14*
-e
-H+
Ar
Ar
H
CO2Me
Me
.
MeO2C
Me
CO2Me
Me
MeO2C
Me
-H
+
.
+
N
N
H
16
Ar
H
MeO2C
Me
CO2Me
Me
-
18
.
- H+
-e
N
H
17
Scheme 3. Suggested mechanism for the photochemistry of dihydropyridines (general formula 14).

3194
E. Fasani et al. / Tetrahedron 64 (2008) 3190e3196
indicated in the photodechlorination and cyclization of some
20-chlorobenzylpyridinium salts.17 Alternatively, it may be
that cyclization by attack of the ester oxygen atom precedes
HCl loss, as has been established in the photoreaction of am-
ides and esters of 2,6-dichlorocynnamic acid to give 5-
chlorocoumarin.18
prismane path in fact well accounts for the positional rear-
rangements in methyl- and dimethylpyridines.8
As for the minor products 9 and 12, their proportion with
respect to 8 and 11 was found to be constant at different de-
grees of conversion, consistently with the fact that these arise
through a single photochemical act with competition between
the two paths, rather than via two subsequent, independent,
photochemical reactions. Their structure did not correspond
to that expected from the alternative Dewar benzene (190)e
prismane path, nor to any benzvalene path, but could be ratio-
nalized as involving a 1,3-shift of the nitrogen atom in Dewar
benzene 21 to give isomeric 22 via diradical 210 (Scheme 5). A
similar mechanism has been previously postulated for the re-
arrangement of methyl 2-pyridinylacetate to methyl anthrany-
late.19 Notice also that a cyclobutenecarboxylate has been
found to add photochemically to nitriles forming an aza Dewar
benzene and a pyridine from it.20
Finally, with the 4-(40-nitrophenyl)pyridine 13 there is no
photocleavable group as in the 20-chlorophenyl analogue,
and the above photorearrangement does not take place, or
at least not with reasonable efficiency. It is possible that
with the nitro group ISC both from the initial excited singlet
to the triplet state (that may have a np* character) and from
the triplet back to the ground state are faster, as it happens for
many nitroaromatics.21 This would shorten the lifetime of
both excited states and leave little room for chemical reac-
tion, since there is no intramolecular H transfer path
available.
.
O
O
.
MeOOC
Me
MeO2C
Me
OMe
Me
OMe
hν
- Cl
6
5
.
.
N
N
Me
- [Me ]
Scheme 4. Photochemical reaction of pyridine 5.
As mentioned, cleavage of the chlorine is observed only
when this is in position 20. With the 30- and 40-chlorophenyl
derivatives, the process occurring is the positional rearrange-
ment of the pyridine substituents. To our knowledge, a single
investigation has been carried out on the photochemistry of
Hantzsch type pyridines,9 where the product structure has
been assigned primarily on the basis of proton exchange ex-
periments in methyl groups in position 2 or 4. More generally,
the rearrangement in pyridines implies the intermediacy of
benzvalene(s) or Dewar benzene(s) and depends on the struc-
ture of the compound irradiated and on conditions, which af-
fect the multiplicity and the electronic configuration of the
reacting excited states. In the present case, the characteristic
pattern of photorearrangement observed in the gas phase
with methylpyridines (i.e., one atom inserts between the two
next neighbors) and attributed to azaprefulvene intermediates
is not observed.8
4. Conclusions
In conclusion, aromatization is a general, although quite in-
efficient, process in the photochemistry of Hantzsch 1,4-dihy-
dropyridines. The efficiency depends on the strength of the
C4eH bond and is increased when a substituent at C4 further
weakens that bond by sterical hindering or electronic effect.
The generally low efficiency of the photoreaction is due to
the short lifetime of the singlet excited state (the triplet has
Examination of the accessible paths shows that the main
products from the two pyridines, that is, 8 and 11, are those
expected from 1,4-ring closure to give Dewar benzene 19
and intramolecular cycloaddition to prismane 20, followed
by the alternative ring opening to the other Dewar benzene
21, which finally reopens to the observed products. The
Ar
CO2Me
MeO2C
CO2Me
MeO2C
Me
Ar CO2Me
Ar
N
Ar
CO2Me
MeO2C
Me
CO2Me
hν
N
N
Me
Me
Me
20
Me
Me
N
Me
19
7,10
21
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
Ar
Ar
CO2Me
Me
N
Ar
N
.
.
N
N
C
Ar
Me
Me
Me
Me
22
CO2Me
9, 12
Me
Me
Me
21'
8, 11
CO2Me
Me
Ar
Cl
Ar =
N
Me
Me
Cl
19'
Scheme 5. Photorearrangement of pyridines 7 and 10.

E. Fasani et al. / Tetrahedron 64 (2008) 3190e3196
3195
no role because of the inefficient ISC). Structural modifica-
5.2.1. Photochemistry of dimethyl 4-(30-chlorophenyl)-1,4-
tions that enhance the lifetime of the singlet may increase
the efficiency of the cleavage. This would make an interesting
photoactivated hydrogen donating system, which would be
valuable because of the strong absorption in the UVA of these
molecules. The process appears to be little affected by the phe-
nyl group in 4 and likewise by susbtituents on that group. An
exception occurs when a different (intramolecular) reaction
comes in, as with the 4-(20-nitrophenyl) derivative that reacts
several orders of magnitude faster. As for the corresponding
phenylpyridines, these undergo photorearrangement of the
benzene ring via Dewar benzene (preferred 1,4-bonding) at
a rate comparable todor larger thandthat of aromatization,
unless a fragmentable group in 20 makes photocleavage of
that group the faster alternative.
dihydro-2,6-dimethyl-3,5-pyridindicarboxylate (2)
Irradiation of this compound for 20 h and separation of raw
photolysate as indicated above gave product 7 as well as
a mixed fraction containing compounds 8 and 9 as a glassy
solid. Anal. Calcd for C17H16ClNO4: C, 61.18; H, 4.89; N,
4.20. Found: C, 61.0; H, 4.9; N, 4.0.
Dimethyl 3-(30-chlorophenyl)-5,6-dimethyl-2,4-pyridindi-
1
carboxylate (8), H NMR (CDCl3) d 2.36 (s, 3H), 2.65 (s,
3H), 3.67 (s, 3H), 3.95 (s, 3H), 7.3 (m, 3H), 7.6 (m, 1H);
13C NMR (CDCl3) d 15.2 (CH3), 23.0 (CH3), 52.0 (CH3),
52.3 (CH3), 122.6 (C, C-3), 126.0 (CH), 126.7 (C, C-5),
128.1 (CH), 128.2 (CH), 128.9 (CH), 133.8 (C), 140.5 (C),
140.8 (C, C-4), 152.7 (C, C-2), 159.8 (C, C-6), 166.9 (C),
167.4 (C).
Dimethyl 6-(30-chlorophenyl)-3,4-dimethyl-2,5-pyridindi-
1
5. Experimental
carboxylate (9), H NMR (CDCl3) d 2.37 (s, 3H), 2.47 (s,
3H), 3.73 (s, 3H), 4.00 (s, 3H); 13C NMR (CDCl3) d 14.7
(CH3), 16.5 (CH3), 52.1 (CH3), 52.3 (CH3), 125.9 (CH),
126.7 (C, C-6), 128.1 (CH), 128.4 (CH), 129.1 (CH), 130.4
(C, C-3), 133.9 (C), 140.2 (C), 145.2 (C, C-4), 149.0 (C,
C-2), 151.7 (C, C-6), 166.4 (C), 168.2 (C).
5.1. General
Compounds 1, 2, 3, and 6 were prepared according to a pub-
lished procedure22 and compound 5 was of commercial origin
(Aldrich, Steiheim, Germany). Absorption spectra were regis-
tered on 5ꢁ10ꢀ5 M solutions in spectrophotometric cuvettes
(1 cm optical path) on the range of 200e450 nm on a Jasco
V-550 UVevis Spectrophotometer, using Spectra Manager
5.2.2. Photochemistry of dimethyl 4-(40-chlorophenyl)-1,4-
dihydro-2,6-dimethyl-3,5-pyridindicarboxylate (3)
Irradiation of this compound for 20 h and separation of raw
photolysate as indicated above gave product 10 as well as
a mixed fraction containing compounds 11 and 12 as a glassy
solid. Anal. Calcd for C17H16ClNO4: C, 61.18; H, 4.89; N,
4.20. Found: C, 59.8; H, 4.9; N, 3.9.
as software UV, with scan rate 1 nm sꢀ1
.
5.2. Photochemistry
Small-scale experiments were carried out on 3 mL samples
of 2.5ꢁ10ꢀ4 M solutions of the dihydropyridines in MeCN or
MeOH in quartz tubes after argon flushing when appropriate.
These were irradiated by means of two or four external lamps,
either 15 W low-pressure mercury arcs (254 nm) or 15 W
phosphor-coated lamps (center of emission 366 nm; midheight
width 35 nm). The course of the reaction was monitored by
TLC (cyclohexane/ethyl acetate 7:3) and by HPLC (Jasco)
by using a Supelco Discovery HS C-18 25 cmꢁ4.6 mm,
5 mm column and eluting with acetonitrile/water mixture
(50:50, flow 1.3 mL/min, lan¼250 nm for compound 1, 2,
and 3; 55:45, flow 0.8 mL/min, lan¼250 nm for compound
5; 70:30, flow 0.5 mL/min, lan¼250 nm for compounds 6).
Retention times were tR 11.3 min (compound 1), tR 13.4 min
(compound 2), tR 14.2 min (compound 3), tR 13.0 min (com-
pound 5), tR 9.7 min (compound 6).
Dimethyl 3-(40-chlorophenyl)-5,6-dimethyl-2,4-pyridindi-
1
carboxylate (11), H NMR (CDCl3) d 2.35 (s, 3H), 2.64 (s,
3H), 3.67 (s, 3H), 3.95 (s, 3H), 7.41 (d, J¼7 Hz, 2H), 7.49
(d, J¼7 Hz, 2H); 13C NMR (CDCl3) d 15.6 (CH3), 23.4
(CH3), 52.5 (CH3), 52.7 (CH3), 122.9 (C, C-3), 126.9 (C,
C-5), 128.4 (CH), 129.6 (CH), 134.8 (C), 137.9 (C), 140.9
(C, C-4), 153.3 (C, C-2), 160.2 (C-6), 167.4 (C), 167.9 (C).
Dimethyl 6-(40-chlorophenyl)-3,4-dimethyl-2,5-pyridindi-
1
carboxylate (12), H NMR (CDCl3) d 2.36 (s, 3H), 2.46 (s,
3H), 3.72 (s, 3H), 3.99 (s, 3H), 7.41 (d, J¼7 Hz, 2H), 7.52
(d, J¼7 Hz, 2H); 13C NMR (CDCl3) d 15.1 (CH3), 15.9
(CH3), 52.5 (CH3), 52.7 (CH3), 126.8 (C, C-5), 128.5 (CH),
129.6 (CH), 130.5 (C, C-3), 134.9 (C), 137.5 (C), 145.7 (C,
C-4), 149.3 (C, C-2), 152.1 (C, C-6), 167.3 (C), 168.1.
Preparative experiments were carried out on 300 mL por-
tions of 5ꢁ10ꢀ3 M solutions of the dihydropyridines in an im-
mersion well apparatus after argon flushing. These were
internally irradiated by means of one 125 W medium pressure
mercury arc through Pyrex until a total conversion was
reached (TLC and HPLC).
Evaporation of the solvent and chromatography afforded
the photoproducts, characterized by examination of their prop-
erties, in particular HPLC, IR, and NMR. Phenylpyridines 5,
6, 7, 10, 13 were identical to samples prepared by literature
procedures.
5.2.3. Structure assignment
The 40-chlorophenyl derivatives were chosen for the de-
tailed assignment, because of the simplified aromatic pattern,
but closely analoguous results were obtained with the 30
substituted compounds. The work was based on NOESY and
HMBC experiments for determining the reciprocal position
of methyl groups and for the assignment of quaternary
carbons.
In the 2D-NOESY experiment no NOE correlation was ob-
served between aromatic hydrogens and any of the methyl
groups in either isomer.

3196
E. Fasani et al. / Tetrahedron 64 (2008) 3190e3196
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12) were correlated with both methyl signals; with 11 the car-
boxyl at d 167.9 correlated with the methyl group at 2.35. The
methyl groups were vicinal, but none of them was vicinal to
the phenyl. In 11 long range correlations between a C
(153.3) and aromatic hydrogens and between C (140.9) and
the methyl (2.3) were observed. Taking into account that the
more deshielded carbons are those a to the pyridine nitrogen,
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in 12 the more deshielded carbon is C-6 (152.1) that shows
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The quantum yields of the reaction were measured in quartz
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propriate, irradiated by means of 12 phosphor-coated lamps
(15 W, center of emission 366 nm; midheight width 35 nm)
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Acknowledgements
Partial financial support of this work by the Department of
Education, Rome, is gratefully acknowledged.
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