Synthesis of 1,4-dihydropyridines and their fluorescence properties

Article abstract of DOI:10.1002/ejoc.201402426

We have successfully synthesized 3,4,5-substituted 1,4-dihydropyridines (1,4-DHPs) from amine hydrochloride salts, aldehydes, and acetals in good yields without the addition of a catalyst. The synthesized 1,4-DHPs exhibit various wavelengths of fluorescen

Full text of DOI:10.1002/ejoc.201402426

FULL PAPER
DOI: 10.1002/ejoc.201402426
Synthesis of 1,4-Dihydropyridines and Their Fluorescence Properties
Shunsuke Sueki,*[a][‡] Ryo Takei,[a] Yuto Zaitsu,[a] Junya Abe,[a] Akane Fukuda,[a]
Keisuke Seto,[b][‡‡] Yukio Furukawa,[b] and Isao Shimizu*[a]
Keywords: Multicomponent reactions / Nitrogen heterocycles / Fluorescence / Cross-coupling
We have successfully synthesized 3,4,5-substituted 1,4-dihy-
dropyridines (1,4-DHPs) from amine hydrochloride salts, al-
dehydes, and acetals in good yields without the addition of
a catalyst. The synthesized 1,4-DHPs exhibit various wave-
lengths of fluorescence, which could be tuned by changing
the substituents at the 3- and 5-positions of the 1,4-DHPs.
also found in nicotinamide adenine dinucleotide phosphate
(NADPH), which is an important redox coenzyme in cells,
as well as in various natural products, for example, guayul-
amine A[2] and aspernigrin A[3] (Figure 1).
Introduction
1,4-Dihydropyridines (1,4-DHPs) are an important class
of biologically active organic compounds, for example, the
calcium channel blocker amlodipine.[1] The DHP scaffold is
1,4-DHPs also have potential as photoelectronic func-
tional materials. For example, 2,6-unsubstituted 1,4-DHPs
exhibit strong blue fluorescence,[4] although 2,6-dimethyl-
1,4-DHP (Hantzsch ester) exhibits no fluorescence. On the
basis of these phenomena, we hypothesized that the fluores-
cence properties of 2,6-unsubstituted DHPs could be con-
trolled by installing 1) various electron-donating functional
groups at the 1-position and 2) various electron-with-
drawing groups (EWGs) at the 3- and 5-positions of DHPs
that would dominate the π-conjugation of the DHP scaffold
and act as electron-accepting moieties (Figure 2).
Figure 1. Examples of a drug and natural products bearing the 1,4-
dihydropyridine scaffold.
[a] Department of Applied Chemistry, School of Advanced Science
and Engineering, Waseda University,
Shinjuku-ku, Tokyo 169-8555, Japan
E-mail: sueki@mol.f.u-tokyo.ac.jp
shimizui@waseda.jp
[b] Department of Chemistry and Biochemistry, School of
Advanced Science and Engineering, Waseda University,
Shinjuku-ku, Tokyo 169-8555, Japan
Figure 2. Design and retrosynthetic scheme for fluorescent 2,6-un-
substituted 1,4-DHPs.
[‡] Current address: Graduate School of Pharmaceutical Sciences,
The University of Tokyo,
Bunkyo-ku, Tokyo 113-0033, Japan.
A number of 1,4-DHP syntheses have been studied to
date, but relatively few methods for the synthesis of 2,6-
unsubstituted 1,4-DHPs have been reported.[5,6] Therefore
we developed a facile method for synthesizing 1,4-DHPs
[‡‡] Current address: Advanced Ultrafast Laser Research Center,
The University of Electro-Communications,
Chofu, Tokyo 182-8585, Japan
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201402426.
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with various functional groups because of their potential as and applicable to the synthesis of 1,4-DHPs bearing cyano
fluorescent probes.[7] In continuation of our efforts towards or nitro groups at the 3- and 5-positions, which is otherwise
the synthesis of 1,4-DHPs, we have also reported a facile difficult to achieve by using the currently known methods.
Yb-catalyzed one-pot synthesis of 1,4-DHPs.[8] This We further evaluated the fluorescence properties of the syn-
method provides 2,6-unsubstituted 1,4-DHPs with various thesized 1,4-DHPs and compared them with related com-
functional groups. The reactions with aliphatic amines or pounds.
ammonia catalyzed by Yb scarcely proceeded, and 1,4-
DHPs with more EWGs, such as cyano or nitro groups, at
the 3- and 5-positions could not be achieved by this
method. Recently Jiang et al. reported the palladium-cata-
lyzed synthesis of 1,4-DHPs, including one example of a
3,5-dicyano-1,4-DHP,[9] and Nishiwaki and and Tobe et al.
reported the synthesis of 3,5-dinitro-1,4-DHPs.[10] Al-
though both syntheses give 1,4-DHPs in good yields, the
substrate scope is limited. To extend the chemical diversity
of 1,4-DHPs, we studied the synthesis of 2,6-unsubstituted
1,4-DHP by using aliphatic amines or ammonia. Interest-
ingly, we found that 1,4-DHPs could be easily synthesized
without the addition of a catalyst by using the correspond-
ing amine hydrochloride salts instead of amines. In this pa-
per we describe a one-pot synthesis of 3,4,5-trisubstituted
1,4-DHPs by using amine hydrochloride salts or ammo-
nium chloride [Equation (1)]. This method is very simple
Results and Discussion
As shown in Equation (1), we initially found that the re-
action with benzylamine hydrochloride (1a),[11] ethyl glyox-
ylate (2a), and ethyl 3,3-diethoxypropionate (3a) proceeded
smoothly to give the corresponding 1,4-DHP 4aa due to
low Lewis basicity of 1a. The reaction was also promoted
by the hydrochloride of 1a. The products of 1,4-DHP syn-
thesis using amine hydrochloride salts are shown in Table 1;
various 1,4-DHPs bearing electron-rich or -deficient aro-
matic rings (4ab–4al) were obtained in moderate-to-satisfac-
tory yields. The reaction was not inhibited by highly polar
functional groups, such as the hydroxy group. Heterocyclic
moieties such as furan and thiophene rings were also intro-
duced at the 4-position of 1,4-DHP (4am and 4an) by using
this method. In our previous method,[8] we were unable to
obtain N-alkyl-1,4-DHPs, but the reaction described herein
with primary and secondary aliphatic amine hydrochlorides
gave the desired DHPs (4ar–4av) in satisfactory yields. Op-
tically active 1,4-DHPs 4ay and 4az were obtained by using
amino acid hydrochloride salts as the amine components.
The method reported herein is also useful for practical
synthesis. When 781 mg of 1b were used as the substrate,
4ao was obtained in 82% yield [1.55 g, Equation (2);
(1) 87.0 mg of 1b were used in Table 1, entry 15].
Table 1. Synthesis of 1,4-DHPs with ethyl 3,3-diethoxypropionate (3a).
c
[a] Determined by chiral HPLC (AD-H). PMB = p-methoxybenzyl, Th = thiophenyl, Hex = cyclohexyl, Naph = naphthyl.
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1,4-Dihydropyridines and Their Fluorescence Properties
(2)
By using this method, bis-DHPs 4b were also synthe-
sized. The reactions performed with dialdehydes 2Ј gave
various phenylene-tethered bis-DHPs 4ba–4bd in moderate
yields (Table 2). The reaction of diamine hydrochloride 1Ј
gave alkyl-linked DHPs 4be and 4bf in yields of 49 and
80%, respectively [Equation (3)].
(3)
Ammonium salts were also used for the synthesis of 1-
hydro-3,4,5-trisubstituted 1,4-DHPs. Ammonium chloride monium tetrafluoroborate is soluble in DMSO, and its use
in DMSO was used and 1-hydro-3,4,5-trisubstituted 1,4- in the reaction gave 1,4-DHP 4ca in 44% yield (entry 5).
DHP 4ca was obtained in 52% yield (Table 3, entry 1). The reaction also proceeded when 1 equiv. of ammonium
When the solvent was changed to 1,4-dioxane, the reaction tetrafluoroborate was used, but the yield of 4ca decreased
did not proceed due to the insolubility of ammonium chlor- to 20% (entry 6). The reaction with ammonium chloride
ide (entry 2). Ammonium acetate also did not provide a sat- and 3a in the absence of benzaldehyde produced 1,4-DHP
isfactory result (entry 3) and the reaction with ammonium 5 and its decarboxylated product 6 in yields of 32 and 17%,
hydrogen carbonate gave a complex mixture (entry 4). Am- respectively (entry 7).[12]
Table 2. Synthesis of 1,3,4,5-tetrasubstituted bis-DHPs with amine hydrochlorides and various dialdehydes.
[a] Diethyl 1-benzyl-4-(4-formylphenyl)-1,4-dihydropyridine-3,5-dicarboxylate (4baЈ) was obtained in 13% yield.
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Table 3. Synthesis of 1-hydro-3,4,5-trisubstituted 1,4-DHPs with ammonium salts.
[a] 1,4-Dioxane was used as solvent; n.r.: no reaction, n.d.: not determined.
To clarify the possibility of the de-esterification of 5 to sion[13] of the ester with chloride anions. Subsequent elimi-
give 6, we treated 5 with ammonium chloride in DMSO at nation of ammonia from the corresponding tetrahydropyr-
90 °C, but 6 was not formed and the starting triester 5 was idine G to afford the decarboxylated product 6 is plausible.
recovered in 98% yield. A plausible reaction mechanism for
The reactions of ammonium chloride, benzaldehydes 2,
the formation of 5 and 6 is shown in Scheme 1. First, in and 3a at 90 °C in DMSO gave various 1,4-DHPs 4c in
the presence of an acid catalyst, ammonium chloride and moderate yields (Table 4).
activated ethyl 3,3-diethoxypropionate reacts to form imine
1-Hydro-3,4,5-trisubstituted 1,4-DHPs 4c are useful in-
A. This imine intermediate A easily tautomerizes into en- termediates in the synthesis of N-substituted 1,4-DHPs.
amine intermediate B and reacts with activated aldehyde to Representative transformations of 4ca with various N-pro-
form enamine C. The subsequent elimination of ethanol tecting reagents are shown in Equation (4). In addition, 4ca
gives α,β-unsaturated imine D. Michael-type annulation of was readily oxidized to give multisubstituted pyridine 7 in
intermediate D and intermediate B yields tetrahydropyr- 89% yield.[14,15]
idine E. Elimination of ammonia from E affords 1,4-DHP
As described above, various 3,4,5-trisubstituted 1,4-
5. As shown above, 6 does not seem to form directly from DHPs with ethoxycarbonyl groups at the 3- and 5-positions
5, but rather from α,β-unsaturated imine D by alkyl fis- have been synthesized. We next studied the synthesis of 1,4-
Scheme 1. Plausible reaction mechanism for the formation of 5 and 6.
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1,4-Dihydropyridines and Their Fluorescence Properties
Table 4. Synthesis of 1-hydro-3,4,5-trisubstituted 1,4-DHPs using groups at the 3- and 5-positions has scarcely been re-
ported.[10,16,17] The structures of 4ek and 4er were identified
ammonium chloride and various benzaldehydes.
by single-crystal X-ray structure analysis (see the Support-
ing Information).[18]
This method was also applied to the reactions of amine
hydrochloride salts with 1,1,3,3-tetraethoxypropane (8), a
highly reactive and unstable malonoaldehyde. 3,5-Diformyl-
ated 1,4-DHPs 4f were obtained in moderate yields by this
method (Table 6).
The transformation of 3,5-diformylated 1,4-DHP is use-
ful for the synthesis of extended π-conjugated DHPs. In the
reaction of 4fa with the Wittig reagent shown in Scheme 2,
3,5-dialkenylated 1,4-DHP 9a was obtained in 95% yield.
On the other hand, Horner–Wadsworth–Emmons reaction
of 4fb or 4fe gave 3,5-bis(substituted-alkenylated) 1,4-DHPs
9b–e in good yields. The structure of 9c was determined by
single-crystal X-ray structure analysis (see the Supporting
Information).[18]
The fluorescence of the synthesized DHPs was measured
in CHCl3 and DMSO (25 μm) following excitation at the
absorption maximum (270–370 nm). The fluorescence
properties of 3,5-bis(ethoxycarbonyl)-1,4-DHPs[19] are sum-
marized in Table 7.
The N-aryl-substituted DHPs bearing electron-donating
groups, such as methoxy or hydroxy, exhibited blue fluores-
cence with good quantum yields (Table 7, entries 1 and 2).
N-[4-(Dimethylamino)phenyl]-1,4-DHP gave a lower quan-
tum yield, but a bathochromic effect was observed (Table 7,
entry 3). DHPs with a nitro group exhibited no fluorescence
[a] Isolated yields based on arylaldehyde 2.
DHPs bearing other EWGs at the 3- and 5-positions. Reac-
tions were performed with various acetals containing
cyano, nitro, acetyl, and benzoyl groups. As shown in
Table 5, the reactions proceeded to give 4e in moderate-to- (Table 7, entries 4 and 15).[20] DHPs with other EWGs, such
good yields. The synthesis of 1,4-DHPs 4ee–4el with nitro as halogen atoms, exhibited weak fluorescence (Table 7, en-
(4)
Scheme 2. Transformations of 4fa, 4fb, and 4fe by using Wittig and Horner–Wadsworth–Emmons reagents.
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Table 5. Synthesis of 3,4,5-trisubstituted 1,4-DHPs with various electron-deficient acetals.
[a] The reaction was carried out by using N,N-dimethyl-1,4-phenylenediamine with Yb(OTf)3 as catalyst instead of with the N,N-dimethyl-
1,4-phenylenediamine hydrochloride salt.
Table 6. Synthesis of 3,5-diformyl-1,4-DHPs with 1,1,3,3-tetra- substituent effects of the N-aryl moiety, with the exception
ethoxypropane (8).
of N-[4-(dimethylamino)phenyl]- and N-(4-iodophenyl)-1,4-
DHP, show a good Hammett correlation (Figure 3). In ge-
neral, the quantum yield of fluorescence decreases due to a
nonradiative transition from the singlet excited state and
intersystem crossing between singlet and triplet excited
states. These factors could not be estimated from the induc-
tive effect, that is, the substituent effects of the DHPs. The
N-alkyl- and 1-hydro-DHPs also exhibited blue fluores-
cence with good quantum yields (Table 7, entries 9–14).
Compared with the results of entries 12–14 in Table 7, the
introduction of methyl or ethoxycarbonylmethyl groups at
the 4-position of DHP did not change the fluorescence
properties of DHPs (Table 7, entries 16 and 17). The quan-
tum yields of the DHPs with benzoyl, allyloxycarbonyl, and
p-tosyl as N-protecting groups were drastically lower and
the fluorescence was quenched, however, with N-tert-butyl-
dimethylsilyl-DHP, a moderate quantum yield was obtained
(Table 7, entries 18–21). We also examined the fluorescence
properties of pyridine 7, but no fluorescence was observed
(Table 7, entry 22). This result shows that the 1,4-di-
hydropydine scaffold is important for strong florescence.
tries 5–7). The fluorescence quantum yield of N-(4-iodo-
The fluorescence properties of 1,4-DHPs bearing other
phenyl)-1,4-DHP is low because of the heavy atom effect EWGs at the 3- and 5-positions were also measured. DHPs
(Table 7, entry 8). The fluorescence quantum yields and with a cyano group at the 3- and 5-positions showed weak
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1,4-Dihydropyridines and Their Fluorescence Properties
Table 7. Fluorescence properties of 3,5-bis(ethoxycarbonyl)-1,4-DHPs with various functional groups.[a]
[a] In CHCl3 (25 μm). [b] Excited at λabs (nm). [c] Relative quantum yields, based on quinine sulfate as the standard (Φq = 0.55).
Notably, DHPs with nitro groups at the 3- and 5-positions
exhibited green fluorescence, but DHPs with nitrophenyl
groups at the 1- or 4-positions exhibited no fluorescence. In
the case of 3,5-diacetyl- and 3,5-diformyl-1,4-DHPs, larger
Stokes shifts were observed compared with those of 1,4-
DHPs bearing ethoxycarbonyl or cyano groups, but they
showed low quantum yields (Table 8, entries 9–14). A ben-
zoyl substituent at the 3- and 5-positions of 1,4-DHPs in-
duced bathochromic effects, especially in the case of a di-
methylamino group (Table 8, entries 15–18).
Based on the results in Table 7 and Table 8, DHPs with
extended π-conjugation were expected to provide a longer
fluorescence wavelength. Indeed, 3,5-dialkenylated 1,4-
DHPs produced green fluorescence (Table 9, entries 1–3),
and 1,4-DHPs with chalcone moieties at the 3- and 5-posi-
tions exhibited orange fluorescence (Table 9, entry 4).
We also measured the fluorescence of 9e in various sol-
vents. Compound 9e exhibited blue fluorescence in CHCl3
Figure 3. Correlation between the fluorescent quantum yields of
the N-aryl-1,4-DHPs and the Hammett constants.
blue fluorescence (Table 8, entries 1–3). Large Stokes shifts (Table 9). In less-polar solvents, such as cyclohexane, 9e ex-
were observed when the substituents at the 3- and 5-posi- hibited a hypochromic effect, and in other polar solvents
tions were changed to nitro groups (Table 8, entries 4–8). (such as ethyl acetate, acetonitrile, and DMSO), it exhibited
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Table 8. Fluorescence properties of 1,4-DHPs with various EWGs at the 3- and 5-positions.[a]
[a] In CHCl3 (25 μm). [b] Excited at λabs [nm]. [c] Relative quantum yields, based on quinine sulfate as the standard (Φq = 0.55).
Table 9. Fluorescence properties of 3,5-dialkenylated 1,4-DHPs.[a]
a bathochromic effect (Table 10 and Figure 4). These results
suggest that the excitation state of 9e is stabilized by polar
solvents.[4e]
[a] In CHCl3 (25 μm). [b] Excited at λabs [nm]. [c] Relative quantum
yields, based on quinine sulfate as the standard (Φq = 0.55).
Figure 4. Fluorescence spectra of 9e in various solvents.
Table 10. Solvatochromism of 9e in various solvents.[a]
[a] 25 μm. [b] Excited at λabs [nm]. [c] Relative quantum yields, based on quinine sulfate as the standard (Φq = 0.55).
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1,4-Dihydropyridines and Their Fluorescence Properties
Table 11. Fluorecence properties of other related 1,4-DHPs.[a]
[a] In CHCl3 (25 μm). [b] Excited at λabs [nm]. [c] Relative quantum yields, based on quinine sulfate as the standard (Φq = 0.55). PMP =
p-methoxyphenyl.
Finally, we investigated the fluorescence properties of
Experimental Section
other related DHPs to clarify the relationship between
General: All reactions were carried out in air except for some reac-
fluorescence and structure of the DHPs. 2,6-Dihydro-1,4-
tions that required an inert atmosphere. Column chromatography
DHP 10 showed strong blue fluorescence, but the fluores-
was performed by using silica gel 60N. 1,1-Diethoxy-2-nitroethane
cence of 11 and Hantzsch ester 12[21] (Table 11, entries 1–3)
was quenched. These results suggest that the excitation
mode of 10, which produced strong fluorescence, allows a
π–π* transition, whereas 11 and 12 showed almost no
fluorescence because the introduction of a freely rotating
alkyl chain into the fluorophore enhances the nonradiative
internal conversion.[22] Interestingly, the fluorescence of 1,4-
dihydronicotinate 13 was weaker than that of 1,4-DHP 4ao
(Table 11, entries 4 and 5), which also suggests that the two
ethoxycarbonyl groups play an important role in producing
strong fluorescence because of efficient conjugation with
the DHP core structure.
(3c),[23] 3,3-dimethoxy-1-phenylpropan-1-one (3da),[24] 1-(4-chloro-
phenyl)-3,3-dimethoxypropan-1-one (3db),[24] 3,3-dimethoxy-1-(4-
methoxyphenyl)propan-1-one (3dc),[24] and diethyl 2-oxo-2-phenyl-
ethylphosphonate[25] were prepared according to literature pro-
cedures. All other reagents and solvents were purchased from Ald-
rich Co., Tokyo Kasei Kogyo Co., and Wako Pure Chemical Indus-
tries, and used without any purification.
1H and 13C NMR spectra were recorded in CDCl3 or [D6]DMSO
with JEOL Lambda 500 and JNM-ECX500 spectrometers. Proton
chemical shifts are reported relative to Me4Si (CDCl3) at δ =
0.00 ppm or residual solvent peaks (CDCl3: δ = 7.26 ppm; [D6]-
DMSO: δ = 2.50 ppm). Carbon chemical shifts are reported relative
to CDCl3 at δ = 77.00 ppm or [D6]DMSO at δ = 39.50 ppm. Multi-
plicities are indicated as br. (broadened), s (singlet), d (doublet), t
(triplet), q (quartet), sept (septet), and m (multiplet). IR spectra
were recorded with Thermo Fisher Scientific Nicolet6700 and
JEOL JIR-WINSPEC 50 FT-IR spectrometers. Bands are charac-
terized as br (broadened), s (strong), m (medium), and w (weak).
The enantiomeric excesses were determined by HPLC analysis con-
ducted with a JASCO HPLC instrument (pump: PU-2080; detec-
tor: UV-2075, measured at 254 nm; chiral column; mobile phase:
2-propanol/n-hexane). High-resolution mass spectra were recorded
with JEOL JMS-SX102A (FAB) or LCQ-DECA (ESI) spectrome-
ters. Elemental analysis was performed by the Material Characteri-
zation Central Laboratory of Waseda University. X-ray crystallo-
graphic analyses were performed with a Rigaku R-AXIS RAPID
diffractometer using graphite-monochromated Mo-Kα radiation.
Optical rotations were measured with a JASCO DIP-1000 polari-
meter.
Conclusions
Amine or quaternary ammonium hydrochloride salts re-
acted with aldehydes and acetals to give 1,4-DHPs without
the addition of a catalyst. The synthesized 1,4-DHPs toler-
ated various functional groups and were produced in good
yields. 3,4,5-Trisubstituted 1,4-DHPs with various func-
tional groups (such as cyano, nitro, acetyl, formyl, benzoyl,
and alkenyl) were also synthesized in satisfactory yields.
This synthetic method is also a useful tool for preparing
2,6-unsubstituted 1,4-DHPs. The synthesized 3,4,5-trisub-
stituted 1,4-DHPs exhibited fluorescence in the range
403–596 nm. We expect that this synthetic strategy and the
fluorescence data will benefit medicinal chemistry and ma-
terials science.
Fluorescence spectra were recorded with an HITACHI F-2500
spectrofluorimeter. To determine the quantum efficiency of fluores-
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cence (Φ), quinine sulfate in H2O (Φ = 0.55) was used as fluores-
cence standard. UV/Vis absorption spectra of solutions were re-
corded with a JASCO V-570 spectrophotometer. The fluorescence
quantum efficiencies were calculated according to Equation (5), in
which F is the area under the fluorescence band [F = ΣIex(λ), with
Iex(λ) the fluorescence intensity at each emission wavelength], A is
the absorbance at the excitation wavelength, and n is the refractive
index of the solvent.[26]
134.5, 135.7, 138.1, 148.2, 148.6, 166.2 ppm. IR (KBr): ν = 3446
˜
(br), 3070 (w), 3031 (w), 2981 (w), 2929 (w), 2904 (w), 1704 (s),
1685 (s), 1571 (s), 1527 (m), 1419 (m), 1363 (w), 1346 (m), 1307
(w), 1295 (w), 1205 (s), 1178 (s), 1085 (w) cm–1. HRMS (FAB):
calcd. for C24H25N2O6 [M + H]+ 437.1713; found 437.1716.
C24H24N2O6 (436.46): calcd. C 66.04, H 5.54, N 6.42; found C
66.19, H 5.58, N 6.54.
Diethyl 1-Benzyl-4-(4-nitrophenyl)-1,4-dihydropyridine-3,5-dicarb-
oxylate (4ad): Yellow powder (185 mg, 62%). 1H NMR (500 MHz,
CDCl3): δ = 1.10 (t, J = 7.1 Hz, 6 H), 3.95–4.04 (m, 4 H), 4.56 (s,
2 H), 4.98 (s, 1 H), 7.23 (d, J = 7.3 Hz, 2 H), 7.27 (s, 2 H), 7.32 (t,
J = 7.3 Hz, 1 H), 7.36 (dd, J = 7.3, 7.3 Hz, 2 H), 7.37 (d, J =
8.6 Hz, 2 H), 8.01 (d, J = 8.6 Hz, 2 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 14.1, 37.7, 58.3, 60.2, 107.9, 123.2, 127.1, 128.5, 129.0,
(5)
To calculate ΦX, the following refractive indexes of the solvents
129.1, 135.8, 138.1, 146.4, 153.5, 166.2 ppm. IR (KBr): ν = 2993
˜
were used:
(w), 2904 (w), 1698 (s), 1664 (w), 1581 (s), 1513 (m), 1417 (w), 1373
(w), 1344 (s), 1284 (m), 1240 (m), 1207 (m), 1186 (s), 1081 (s), 1029
(w), 983 (w), 852 (w), 827 (w), 754 (w), 725 (w) cm–1. HRMS
(FAB): calcd. for C24H25N2O6 [M + H]+ 437.1713; found 437.1718.
Diethyl 1-Benzyl-4-(2-chlorophenyl)-1,4-dihydropyridine-3,5-dicarb-
oxylate (4ae): Pale-yellow crystal (167 mg, 78%). 1H NMR
(500 MHz, CDCl3): δ = 1.10 (t, J = 7.1 Hz, 6 H), 3.98–4.04 (m, 4
H), 4.53 (s, 2 H), 5.35 (s, 1 H), 7.01 (td, J = 7.7, 1.7 Hz, 1 H), 7.08
(td, J = 7.7, 1.3 Hz, 1 H), 7.21 (dd, J = 7.7, 1.3 Hz, 1 H), 7.24 (dd,
J = 7.7, 1.7 Hz, 1 H), 7.26–7.28 (m, 4 H, aromatic H), 7.32 (t, J =
7.2 Hz, 1 H), 7.38 (dd, J = 7.5, 7.2 Hz, 2 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 14.0, 34.6, 58.1, 60.0, 108.8, 126.6, 127.2,
127.3, 128.3, 128.9, 129.0, 131.3, 132.7, 135.9, 138.0, 144.5,
General Procedure for the One-Pot Synthesis of Dihydropyridine 4a:
A mixture of amine hydrochloride salt (1.0 equiv.), ethyl 3,3-di-
ethoxypropionate (2.5 equiv.), and aldehyde (1.1 equiv.) in DMSO
(1.5 mL/1 equiv.) was stirred at 90 °C for 6–17 h. After the reaction,
the resulting mixture was washed with PBS buffer solution (25 mL)
and extracted with CH2Cl2 (3ϫ 15 mL). The organic layer was
dried with MgSO4. Removal of the solvent in vacuo followed by
column chromatography on silica gel (AcOEt/n-hexane or CHCl3/
MeOH) afforded dihydropyridine 4a.
166.7 ppm. IR (KBr): ν = 3064 (w), 2987 (w), 2933 (w), 1702 (s),
˜
1681 (s), 1658 (w), 1573 (s), 1473 (w), 1419 (m), 1388 (w), 1365 (w),
1307 (m), 1284 (w), 1230 (m), 1172 (s), 1078 (m), 1033 (m), 908
(w), 836 (w), 759 (m), 703 (m), 647 (w), 609 (w), 570 (w), 514
(w) cm–1. HRMS (FAB): calcd. for C24H25ClNO4 [M + H]+
426.1472; found 426.1459.
Triethyl 1-Benzyl-1,4-dihydropyridine-3,4,5-tricarboxylate (4aa):
Yellow powder (120 mg, 62%). H NMR (500 MHz, CDCl3): δ =
1
1.24 (t, J = 7.4 Hz, 3 H), 1.27 (t, J = 7.4 Hz, 6 H), 4.14 (q, J =
7.4 Hz, 2 H), 4.12–4.25 (m, 4 H), 4.57 (s, 2 H), 4.68 (s, 1 H), 7.23
(d, J = 6.8 Hz, 2 H), 7.26 (s, 2 H), 7.32 (t, J = 7.7 Hz, 1 H), 7.38
(dd, J = 6.8, 7.7 Hz, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ =
14.0, 14.2, 38.3, 58.0, 60.3, 60.9, 104.2, 126.8, 128.1, 129.0, 135.8,
Diethyl 1-Benzyl-4-(3-chlorophenyl)-1,4-dihydropyridine-3,5-dicarb-
oxylate (4af): Pale-yellow crystal (148 mg, 69%). 1H NMR
(500 MHz, CDCl3): δ = 1.08 (t, J = 7.1 Hz, 6 H), 3.91–4.04 (m, 4
H), 4.48 (s, 2 H), 4.82 (s, 1 H), 7.02 (tt, J = 8.0, 1.8 Hz, 1 H), 7.05
(dd, J = 8.0, 7.3 Hz, 1 H), 7.11 (d, J = 7.3 Hz, 1 H), 7.17 (s, 1 H),
7.19 (d, J = 7.8 Hz, 2 H), 7.20 (s, 2 H), 7.25 (t, J = 7.1 Hz, 1 H),
7.32 (dd, J = 7.8, 7.1 Hz, 2 H) ppm. 13C NMR (125 MHz, CDCl3):
δ = 14.0, 37.2, 58.2, 60.0, 108.4, 126.4, 127.0, 128.3, 128.29, 128.34,
139.2, 166.5, 173.0 ppm. IR (KBr): ν = 3405 (br), 2981 (w), 2937
˜
(w), 2906 (w), 1731 (s), 1702 (s), 1627 (w), 1581 (w), 1456 (w), 1369
(w), 1278 (m), 1189 (s), 1093 (m), 1078 (m), 1029 (m) cm–1. HRMS
(FAB): calcd. for C21H26NO6 [M + H]+ 388.1760; found 388.1730.
Diethyl
1-Benzyl-4-phenyl-1,4-dihydropyridine-3,5-dicarboxylate
(4ab): Yellow powder (130 mg, 66%). 1H NMR (500 MHz, CDCl3):
δ = 1.08 (t, J = 7.1 Hz, 6 H), 3.93–4.03 (m, 4 H), 4.49 (s, 2 H), 4.83
(s, 1 H), 7.05 (t, J = 7.1 Hz, 1 H), 7.13 (t, J = 7.7 Hz, 2 H), 7.20–
7.23 (m, 6 H, aromatic H), 7.28 (t, J = 7.3 Hz, 1 H), 7.33 (t, J =
7.3 Hz, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 14.1, 37.3,
58.2, 60.0, 109.0, 126.3, 127.2, 127.8, 128.2, 128.3, 129.1, 136.1,
128.9, 129.1, 133.7, 136.0, 137.8, 148.4, 166.5 ppm. IR (KBr): ν =
˜
3079 (w), 3064 (w), 2983 (m), 2935 (m), 2906 (w), 2875 (w), 1706
(s), 1689 (s), 1664 (m), 1577 (s), 1471 (m), 1415 (s), 1388 (m), 1365
(m), 1303 (s), 1284 (m), 1228 (s), 1170 (s), 1089 (m), 1078 (s), 1033
(m), 910 (m), 775 (m), 767 (m), 752 (m), 738 (m), 711 (m), 700 (m),
611 (w), 568 (w) cm–1. HRMS (FAB): calcd. for C24H25ClNO4 [M
+ H]+ 426.1472; found 426.1459.
137.5, 146.5, 166.8 ppm. IR (KBr): ν = 3440 (br), 3077 (w), 3062
˜
(w), 3029 (w), 2987 (w), 2973 (w), 2954 (w), 2939 (w), 2904 (w),
1693 (s), 1662 (s), 1577 (s), 1494 (w), 1456 (w), 1446 (w), 1417 (m),
1390 (w), 1373 (m), 1365 (w), 1315 (w), 1303 (w), 1284 (m), 1245
(m), 1205 (s), 1187 (s), 1112 (w), 1085 (w), 1024 (w), 991 (w), 755
(w), 736 (w), 717 (w), 698 (w) cm–1. HRMS (FAB): calcd. for
C24H26NO4 [M + H]+ 392.1862; found 392.1869.
Diethyl 1-Benzyl-4-(4-chlorophenyl)-1,4-dihydropyridine-3,5-dicarb-
oxylate (4ag): Yellow oil (160 mg, 75%). 1H NMR (500 MHz,
CDCl3): δ = 1.12 (t, J = 7.1 Hz, 6 H), 3.96–4.05 (m, 4 H), 4.52 (s,
2 H), 4.85 (s, 1 H), 7.13 (d, J = 8.4 Hz, 2 H), 7.17 (d, J = 8.4 Hz,
2 H), 7.22 (d, J = 6.8 Hz, 2 H), 7.24 (s, 2 H), 7.30 (t, J = 7.2 Hz,
1 H), 7.35 (dd, J = 7.2, 6.8 Hz, 2 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 14.0, 36.8, 58.2, 60.0, 108.6, 127.1, 127.9, 128.3, 129.0,
Diethyl 1-Benzyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarb-
1
oxylate (4ac): Yellow powder (174 mg, 80%). H NMR (500 MHz,
CDCl3): δ = 1.17 (t, J = 7.9 Hz, 6 H), 4.00–4.13 (m, 4 H), 4.63 (s,
2 H), 5.04 (s, 1 H), 7.32 (s, 2 H), 7.33 (d, J = 7.4 Hz, 2 H), 7.38
(dd, J = 7.4, 7.9 Hz, 2 H), 7.47, (t, J = 7.9 Hz, 1 H), 7.47 (dd, J =
129.5, 131.9, 136.0, 137.6, 145.0, 166.5 ppm. IR (KBr): ν = 3438
(br), 3031 (w), 2981 (w), 2935 (w), 2904 (w), 2360 (w), 1700 (s),
1629 (w), 1583 (m), 1488 (m), 1456 (w), 1411 (m), 1390 (m), 1371
˜
7.9, 7.9 Hz, 1 H), 7.68 (d, J = 7.9 Hz, 1 H), 8.02 (d, J = 7.9 Hz, 1 (m), 1303 (m), 1278 (m), 1230 (s), 1187 (s), 1076 (s), 1014 (m),
H), 8.15 (s, 1 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 14.0,
37.4, 58.2, 60.1, 107.9, 121.4, 123.0, 127.0, 128.3, 128.4, 129.1,
842 (w), 825 (w), 759 (w), 698 (w) cm–1. HRMS (FAB): calcd. for
C24H23ClNO4 [M – H]+ 424.1316; found 424.1310.
5290
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© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 5281–5301

1,4-Dihydropyridines and Their Fluorescence Properties
Diethyl
1-Benzyl-4-(3-hydroxyphenyl)-1,4-dihydropyridine-3,5-di-
J = 8.6 Hz, 2 H), 7.24 (s, 2 H), 7.25 (d, J = 7.6 Hz, 2 H), 7.32 (t,
1
carboxylate (4ah): Yellow oil (107 mg, 54%). H NMR (500 MHz, J = 7.6 Hz, 1 H), 7.38 (dd, J = 7.6, 7.6 Hz, 2 H) ppm. 13C NMR
CDCl3): δ = 1.13 (t, J = 7.1 Hz, 6 H), 3.99–4.11 (m, 4 H), 4.49 (s,
2 H), 4.84 (s, 1 H), 6.40 (br. s, 1 H), 6.62 (ddd, J = 7.9, 2.6, 0.92 Hz,
1 H), 6.80–6.83 (m, 2 H), 7.04 (t, J = 7.9 Hz, 1 H), 7.24 (d, J =
(125 MHz, CDCl3): δ = 14.1, 36.4, 55.0, 58.1, 60.0, 109.1, 113.1,
127.1, 128.2, 129.0, 129.1, 136.2, 137.3, 139.1, 158.0, 166.8 ppm.
IR (KBr): ν = 3372 (br), 2979 (m), 2935 (w), 2904 (w), 2834 (w),
˜
7.0 Hz, 2 H), 7.27 (s, 2 H), 7.32 (t, J = 7.3 Hz, 1 H), 7.37 (dd, J = 1700 (s), 1608 (m), 1583 (s), 1508 (s), 1454 (m), 1413 (m), 1390 (m),
7.3, 7.0 Hz, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 14.0,
37.1, 58.1, 60.2, 108.8, 113.5, 115.4, 120.1, 127.2, 128.2, 128.8,
1371 (m), 1301 (m), 1278 (s), 1234 (s), 1174 (s), 1076 (s), 1031 (m),
975 (w), 904 (w), 846 (w), 827 (m), 752 (m), 700 (m) cm–1. HRMS
(FAB): calcd. for C25H27NNaO5 [M + Na]+ 444.1781; found
444.1781.
129.0, 136.0, 137.7, 148.0, 155.9, 167.1 ppm. IR (KBr): ν = 3396
˜
(br), 3083 (w), 3031 (w), 2983 (w), 2954 (w), 2902 (w), 1691 (s),
1664 (s), 1556 (s), 1477 (w), 1452 (w), 1423 (w), 1380 (w), 1365 (w),
1351 (w), 1311 (m), 1205 (s), 1186 (s), 1083 (w), 1033 (w), 1024 (w),
991 (w), 962 (w), 927 (w), 806 (w), 796 (w), 725 (w), 690 (w) cm–1.
HRMS (FAB): calcd. for C24H26NO5 [M + H]+ 408.1811; found
408.1813.
Diethyl 1-Benzyl-4-(furan-2-yl)-1,4-dihydropyridine-3,5-dicarboxyl-
ate (4am): Yellow crystal (90 mg, 47%). 1H NMR (500 MHz,
CDCl3): δ = 1.22 (t, J = 7.1 Hz, 6 H), 4.07–4.20 (m, 4 H), 4.60 (s,
2 H), 5.09 (s, 1 H), 6.06 (d, J = 3.1 Hz, 1 H), 6.25 (dd, J = 3.1,
1.8 Hz, 1 H), 7.25 (d, J = 1.8 Hz, 1 H), 7.27 (s, 2 H), 7.28 (d, J =
7.7 Hz, 2 H), 7.32 (t, J = 7.3 Hz, 1 H), 7.38 (dd, J = 7.7, 7.3 Hz, 2
H) ppm. 13C NMR (125 MHz, CDCl3): δ = 14.3, 31.0, 58.2, 60.1,
105.4, 105.9, 110.3, 126.9, 128.2, 129.0, 136.3, 138.5, 141.0, 157.7,
Diethyl 1-Benzyl-4-(4-cyanophenyl)-1,4-dihydropyridine-3,5-dicarb-
oxylate (4ai): Yellow oil (105 mg, 50%). 1H NMR (500 MHz,
CDCl3): δ = 1.16 (t, J = 7.0 Hz, 6 H), 4.01–4.12 (m, 4 H), 4.60 (s,
2 H), 4.97 (s, 1 H), 7.28 (d, J = 7.3 Hz, 2 H), 7.31 (s, 2 H), 7.38 (d,
166.7 ppm. IR (KBr): ν = 3446 (br), 3079 (w), 3066 (w), 3033 (w),
˜
J = 8.2 Hz, 2 H), 7.39 (t, J = 6.4 Hz, 1 H), 7.40 (dd, J = 7.3, 6.4 Hz, 2985 (w), 2958 (w), 2940 (w), 2908 (w), 1697 (s), 1683 (s), 1664 (s),
2 H), 7.50 (d, J = 8.2 Hz, 2 H) ppm. 13C NMR (125 MHz, CDCl3): 1579 (s), 1496 (w), 1456 (w), 1446 (w), 1419 (m), 1373 (m), 1365
δ = 14.1, 37.8, 58.3, 60.1, 108.0, 110.0, 119.0, 127.1, 128.5, 128.7,
(m), 1282 (s), 1241 (w), 1207 (w), 1184 (s), 1112 (w), 1078 (s), 1022
(w), 1010 (w), 933 (w), 950 (w), 804 (m), 732 (m), 694 (m) cm–1.
HRMS (FAB): calcd. for C22H23NNaO5 [M + Na]+ 404.1468;
129.1, 131.7, 135.8, 138.0, 151.5, 166.3 ppm. IR (KBr): ν = 3064
˜
(br), 3033 (w), 2983 (w), 2937 (w), 2902 (w), 2873 (w), 2227 (m),
1700 (s), 1627 (w), 2604 (w), 1581 (m), 1454 (w), 1371 (w), 1278 found 404.1468.
(w), 1232 (m), 1187 (s), 1076 (m), 1022 (w), 773 (w), 700 (w) cm–1.
Diethyl 1-Benzyl-4-(thiophen-3-yl)-1,4-dihydropyridine-3,5-dicarb-
HRMS (FAB): calcd. for C25H24N2NaO4 [M + Na]+ 439.1628;
found 439.1628.
oxylate (4an): Yellow crystal (81 mg, 40%). 1H NMR (500 MHz,
CDCl3): δ = 1.11 (t, J = 7.1 Hz, 6 H), 3.98–4.09 (m, 4 H), 4.48 (s,
2 H), 4.98 (s, 1 H), 6.89 (d, J = 2.9 Hz, 1 H), 6.92 (dd, J = 4.9,
Diethyl 1-Benzyl-4-(2-methoxyphenyl)-1,4-dihydropyridine-3,5-di-
carboxylate (4aj): Pale-yellow crystal (114 mg, 54%). 1H NMR 1.1 Hz, 1 H), 7.04 (tt, J = 4.9, 2.9 Hz, 1 H), 7.15 (d, J = 7.0 Hz, 2
(500 MHz, CDCl3): δ = 1.11 (t, J = 7.1 Hz, 6 H), 3.71 (s, 3 H), H), 7.17 (s, 2 H), 7.25 (t, J = 7.6 Hz, 1 H), 7.30 (dd, J = 7.6, 7.0 Hz,
3.94–4.05 (m, 4 H), 4.53 (s, 2 H), 5.22 (s, 1 H), 6.76 (dd, J = 7.5,
7.4 Hz, 1 H), 6.80 (td, J = 7.5, 1.5 Hz, 1 H), 7.09 (dd, J = 7.4, 108.4, 121.2, 124.6, 127.0, 127.7, 128.2, 129.0, 136.2, 137.6, 147.3,
1.5 Hz, 1 H), 7.19 (dd, J = 7.4, 1.5 Hz, 1 H), 7.24 (s, 2 H), 7.29 (d, 166.8 ppm. IR (KBr): ν = 3122 (w), 3102 (w), 3029 (w), 2983 (w),
2 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 14.2, 32.1, 58.2, 60.0,
˜
J = 6.9 Hz, 2 H), 7.33 (t, J = 7.8 Hz, 2 H), 7.39 (dd, J = 7.8, 6.9 Hz, 2935 (w), 2896 (w), 1695 (s), 1681 (s), 1573 (s), 1494 (w), 1456 (w),
2 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 14.0, 32.2, 55.3, 58.1,
1419 (m), 1388 (w), 1378 (w), 1357 (w), 1311 (m), 1278 (m), 1189
60.0, 108.6, 110.1, 120.1, 127.3, 127.5, 128.2, 129.0, 131.0, 135.0,
(s), 1170 (s), 1078 (m), 1027 (w), 784 (m) cm–1. HRMS (FAB):
136.2, 138.0, 157.0, 167.1 ppm. IR (KBr): ν = 3066 (w), 3027 (w), calcd. for C22H23NNaO4S [M + Na]+ 420.1237; found 420.1240.
˜
2977 (w), 2942 (w), 2898 (w), 1698 (s), 1679 (s), 1571 (s), 1494 (m),
Diethyl 1-(4-Methoxybenzyl)-4-phenyl-1,4-dihydropyridine-3,5-di-
1454 (w), 1419 (m), 1388 (w), 1365 (w), 1303 (m), 1263 (w), 1245
carboxylate (4ao): Yellow solid (351 mg, 83%). 1H NMR
(w), 1199 (s), 1172 (s), 1083 (m), 1029 (m), 989 (w), 854 (w), 779
(500 MHz, CDCl3): δ = 1.16 (t, J = 7.4 Hz, 6 H), 3.82 (s, 3 H),
(w), 750 (m), 723 (w) cm–1. HRMS (FAB): calcd. for C25H27NO5
3.99–4.11 (m, 4 H), 4.51 (s, 2 H), 4.89 (s, 1 H), 6.93 (d, J = 8.3 Hz,
[M]+ 421.1889; found 421.1873. C25H27NO5 (421.49): calcd. C
2 H), 7.12 (t, J = 7.4 Hz, 1 H), 7.20 (dd, J = 7.4, 6.8 Hz, 2 H), 7.21
71.24, H 6.46, N 3.32; found C 71.27, H 6.44, N 3.30.
(d, J = 8.3 Hz, 2 H), 7.26 (s, 2 H), 7.26 (d, J = 6.8 Hz, 2 H) ppm.
Diethyl 1-Benzyl-4-(3-methoxyphenyl)-1,4-dihydropyridine-3,5-di-
carboxylate (4ak): Yellow oil (142 mg, 67%). H NMR (500 MHz,
13C NMR (125 MHz, CDCl3): δ = 14.1, 37.4, 55.3, 57.8, 60.3,
109.0, 114.5, 126.3, 127.8, 128.1, 128.2, 128.7, 137.5, 146.6, 159.6,
1
CDCl3): δ = 1.13 (t, J = 7.1 Hz, 6 H), 3.66 (s, 3 H), 3.96–4.09 (m,
166.9 ppm. IR (neat): ν = 3056 (w), 2987 (w), 2929 (w), 2838 (w),
˜
4 H), 4.51 (s, 2 H), 4.86 (s, 1 H), 6.64 (dd, J = 7.4, 2.6 Hz, 1 H), 1700 (m), 1683 (m), 1615 (w), 1572 (m), 1513 (m), 1443 (m), 1420
6.81 (dd, J = 2.6, 1.4 Hz, 1 H), 6.86 (dd, J = 7.9, 1.4 Hz, 1 H), 7.08
(dd, J = 7.9, 7.4 Hz, 1 H), 7.23 (d, J = 6.8 Hz, 2 H), 7.24 (s, 2 H),
7.29 (t, J = 7.4 Hz, 1 H), 7.34 (dd, J = 7.4, 6.8 Hz, 2 H) ppm. 13C
NMR (125 MHz, CDCl3): δ = 14.1, 37.2, 54.9, 58.1, 59.9, 108.8,
111.8, 113.8, 120.1, 127.1, 128.2, 128.6, 129.0, 136.1, 137.5, 148.0,
(m), 1387 (m), 1365 (m), 1306 (m), 1290 (m), 1246 (m), 1201 (m),
1170 (s), 1103 (m), 1078 (m), 1026 (m), 985 (m), 947 (m), 927 (m),
916 (m), 835 (m), 814 (m), 804 (m), 753 (m), 723 (m), 698 (m), 622
(w), 608 (m), 540 (m) cm–1. HRMS (FAB): calcd. for
C25H27NNaO5 [M + Na]+ 444.1787; found 444.1774.
159.3, 166.7 ppm. IR (KBr): ν = 3064 (w), 3029 (w), 2981 (w), 2937
˜
Diethyl 1-(4-Methoxybenzyl)-4-(4-methoxyphenyl)-1,4-dihydropyr-
idine-3,5-dicarboxylate (4ap): Yellow oil (75 mg, 33%). 1H NMR
(500 MHz, CDCl3): δ = 1.17 (t, J = 7.3 Hz, 6 H), 3.75 (s, 3 H),
3.82 (s, 3 H), 4.00–4.10 (m, 4 H), 4.50 (s, 2 H), 4.83 (s, 1 H), 6.74
(d, J = 9.0 Hz, 2 H), 6.93 (d, J = 8.3 Hz, 2 H), 7.17 (d, J = 9.0 Hz,
2 H), 7.21 (d, J = 8.3 Hz, 2 H), 7.24 (s, 2 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 14.5, 36.7, 55.4, 55.6, 58.1, 60.2, 109.4,
113.5, 114.7, 128.4, 128.9, 129.4, 137.5, 139.5, 158.3, 159.9,
(w), 2906 (w), 2834 (w), 1700 (s), 1581 (m), 1484 (w), 1454 (w),
1411 (w), 1371 (w), 1276 (w), 1228 (m), 1187 (s), 1076 (m), 1029
(w), 782 (w), 696 (w) cm–1. HRMS (FAB): calcd. for C25H27NO5
[M]+ 421.1889; found 421.1895.
Diethyl 1-Benzyl-4-(4-methoxyphenyl)-1,4-dihydropyridine-3,5-di-
1
carboxylate (4al): Yellow oil (125 mg, 59%). H NMR (500 MHz,
CDCl3): δ = 1.15 (t, J = 7.0 Hz, 6 H), 3.72 (s, 3 H), 3.99–4.10 (m,
4 H), 4.54 (s, 2 H), 4.84 (s, 1 H), 6.73 (d, J = 8.6 Hz, 2 H), 7.18 (d,
167.3 ppm. IR (neat): ν = 2975 (w), 2925 (w), 2900 (w), 2833 (w),
˜
Eur. J. Org. Chem. 2014, 5281–5301
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5291

S. Sueki, I. Shimizu et al.
FULL PAPER
1727 (m), 1698 (s), 1613 (w), 1574 (m), 1515 (m), 1247 (s), 1178 (s), Diethyl 1-Cyclohexyl-4-phenyl-1,4-dihydropyridine-3,5-dicarboxyl-
1074 (s), 1019 (m), 975 (w), 916 (w), 826 (w), 757 (w), 614 (w) cm–1.
HRMS (ESI): calcd. for C23H29NNaO7 [M + Na]+ 454.1842; found
454.1824.
ate (4au): Orange solid (119 mg, 62%). 1H NMR (500 MHz,
CDCl3): δ = 1.18 (t, J = 7.4 Hz, 6 H), 1.24–1.42 (m, 3 H), 1.54 (q,
J = 12.4, 3.4 Hz, 1 H), 1.59 (q, J = 12.4, 3.4 Hz, 1 H) , 1.71 (d, J
= 10.9 Hz, 1 H), 1.92 (d, J = 12.3 Hz, 2 H), 1.98 (d, J = 11.8 Hz,
1 H), 3.24 (tt, J = 11.8, 3.4 Hz, 1 H), 4.01–4.13 (m, 4 H), 4.89 (s,
1 H), 7.12 (t, J = 7.4 Hz, 1 H), 7.22 (dd, J = 8.0, 7.4 Hz, 2 H), 7.28
(d, J = 8.0 Hz, 2 H), 7.29 (s, 2 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 14.2, 25.0, 25.5, 32.5, 37.8, 59.9, 63.6, 108.4, 126.2,
Diethyl 1-[4-(Dimethylamino)phenyl]-4-phenyl-1,4-dihydropyridine-
3,5-dicarboxylate (4aq): Orange solid (55 mg, 26%). 1H NMR
(500 MHz, CDCl3): δ = 1.18 (t, J = 7.4 Hz, 6 H), 2.98 (s, 6 H),
4.02–4.15 (m, 4 H), 4.95 (s, 1 H), 6.74 (d, J = 10.2 Hz, 2 H), 7.14–
7.17 (m, 3 H), 7.26 (t, J = 7.4 Hz, 2 H), 7.39 (d, J = 7.9 Hz, 2 H),
7.54 (s, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 14.2, 37.5,
40.6, 60.0, 109.6, 112.9, 122.8, 126.4, 127.9, 128.3, 130.1, 136.8,
127.8, 128.1, 135.9, 147.0, 167.1 ppm. IR (neat): ν = 2979 (w), 2929
˜
(br), 2854 (w), 1693 (s), 1661 (w), 1581 (s), 1467 (w), 1446 (w), 1416
(w), 1389 (w), 1366 (w), 1354 (w), 1294 (w), 1277 (w), 1267 (w),
1244 (w), 1198 (s), 1184 (s), 1156 (s), 1140 (s), 1094 (m), 1070 (s),
1026 (m), 907 (w), 891 (w), 862 (w), 835 (w), 814 (w), 757 (w), 749
(m), 719 (m), 696 (m), 673 (w), 626 (w), 605 (w) cm–1. HRMS
(FAB): calcd. for C23H30NO4 [M + H]+ 384.2175; found 384.2164.
146.5, 149.3, 167.0 ppm. IR (neat): ν = 2979 (w), 2905 (w), 1698
˜
(s), 1663 (w), 1580 (m), 1567 (w), 1519 (m), 1489 (w), 1477 (w),
1450 (w), 1343 (m), 1325 (w), 1272 (m), 1229 (s), 1189 (s), 1105
(w), 1062 (w), 1024 (m), 943 (w), 906 (w), 865 (w), 836 (w), 821
(m), 777 (w), 750 (m), 727 (w), 711 (w), 698 (m), 646 (w), 612 (w),
567 (w), 542 (m) cm–1. HRMS (ESI): calcd. for C25H28N2O4 [M]+ Diethyl 1-Isopropyl-4-phenyl-1,4-dihydropyridine-3,5-dicarboxylate
1
420.2049; found 420.2032.
(4av): Yellow solid (88 mg, 51%). H NMR (500 MHz, CDCl3): δ
= 1.11 (t, J = 7.4 Hz, 6 H), 1.30 (d, J = 6.8 Hz, 6 H), 3.63 (sept, J
= 6.8 Hz, 1 H), 3.94–4.06 (m, 4 H), 4.82 (s, 1 H), 7.05 (t, J =
7.4 Hz, 1 H), 7.15 (dd, J = 7.4, 6.8 Hz, 1 H), 7.32 (d, J = 6.8 Hz,
2 H), 7.22 (s, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 14.2,
22.0, 37.9, 55.5, 59.9, 108.6, 126.2, 127.8, 128.1, 135.4, 146.9,
Diethyl
4-(Naphthalen-1-yl)-1-[(naphthalen-2-yl)methyl]-1,4-di-
hydropyridine-3,5-dicarboxylate (4ar): Yellow crystal (247 mg,
1
73%). H NMR (500 MHz, CDCl3): δ = 1.14 (t, J = 7.0 Hz, 6 H),
3.97–4.08 (m, 4 H), 5.09 (s, 2 H), 5.10 (s, 1 H), 7.36–7.38 (m, 1 H),
7.39 (s, 2 H), 7.47–7.53 (m, 4 H), 7.57–7.66 (m, 5 H), 7.73–7.75 (m,
1 H), 7.91 (d, J = 7.9 Hz, 1 H), 7.95–7.98 (m, 2 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 14.2, 37.7, 56.3, 60.1, 109.1, 122.6, 125.2,
125.5 (2 C), 126.3, 126.4, 126.9, 127.0, 127.3, 127.4, 127.9, 129.2,
129.4, 130.9, 131.2, 132.4, 133.4, 134.0, 137.5 (2 C), 144.2,
167.1 ppm. IR (neat): ν = 2981 (w), 1689 (s), 1574 (s), 1433 (m),
˜
1391 (w), 1365 (m), 1301 (m), 1273 (w), 1246 (w), 1246 (w), 1181
(s), 1147 (s), 1094 (w), 1071 (s), 1026 (s), 927 (w), 907 (w), 870 (w),
833 (m), 760 (w), 748 (s), 723 (s), 696 (s), 648 (w), 615 (w), 573
(w) cm–1. HRMS (FAB): calcd. for C20H26NO4 [M + H]+ 344.1862;
found 344.1856.
166.9 ppm. IR (KBr): ν = 3058 (w), 2981 (w), 2950 (w), 2935 (w),
˜
2900 (w), 1697 (s), 1664 (s), 1577 (s), 1508 (m), 1475 (w), 1457 (w),
1442 (w), 1415 (s), 1388 (s), 1371 (s), 1319 (m), 1282 (s), 1243 (s),
1186 (s), 1076 (s), 1029 (w), 1014 (w), 983 (w), 927 (w), 914 (w),
856 (w), 786 (s), 771 (w), 748 (m) cm–1. HRMS (FAB): calcd. for
C32H29NO4 [M]+ 491.2097; found 491.2086.
Diethyl 1-(2-Hydroxyethyl)-4-phenyl-1,4-dihydropyridine-3,5-dicarb-
oxylate (4aw): Brown solid (108 mg, 62%). 1H NMR (500 MHz,
CDCl3): δ = 1.18 (t, J = 7.4 Hz, 6 H), 1.79 (br. s, 1 H), 3.52 (t, J
= 5.1 Hz, 2 H), 3.80–3.89 (br. s, 2 H), 4.01–4.14 (m, 4 H), 4.87 (s,
1 H), 7.13 (t, J = 7.4 Hz, 1 H), 7.23 (dd, J = 7.4, 6.8 Hz, 2 H), 7.25
(s, 2 H), 7.32 (d, J = 6.8 Hz, 2 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 14.2, 37.3, 56.5, 60.0, 61.6, 108.7, 126.3, 127.9, 128.2,
Diethyl 4-Phenyl-1-[(pyren-1-yl)methyl]-1,4-dihydropyridine-3,5-di-
carboxylate (4as): Yellow solid (146 mg, 57%). 1H NMR
(500 MHz, CDCl3): δ = 1.01 (t, J = 7.4 Hz, 6 H), 3.85–3.98 (m, 4
H), 4.84 (s, 1 H), 5.01 (s, 2 H), 6.97 (t, J = 7.4 Hz, 1 H), 7.03 (dd,
J = 7.4, 7.4 Hz, 2 H), 7.18 (d, J = 7.4 Hz, 2 H), 7.25 (s, 2 H), 7.71
(d, J = 7.7 Hz, 1 H), 7.85–7.91 (m, 4 H), 7.98 (dd, J = 9.1, 6.8 Hz,
2 H), 8.05 (dd, J = 7.7, 6.8 Hz, 2 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 14.1, 37.5, 56.1, 59.9, 109.1, 121.6, 124.4, 124.8, 124.9,
125.5, 125.7, 126.1, 126.2, 127.2, 127.7, 127.8 (2 C), 128.19, 128.23
(2 C), 128.4, 130.4, 131.1, 131.5, 137.4, 146.4, 166.8 ppm. IR (neat):
137.8, 146.7, 167.1 ppm. IR (KBr): ν = 3465 (br), 3066 (w), 2986
˜
(w), 2872 (w), 1696 (m), 1664 (m), 1561 (m), 1491 (w), 1450 (w),
1417 (w), 1390 (w), 1363 (w), 1301 (m), 1254 (w), 1281 (m), 1170
(s), 1080 (m), 1046 (s), 1028 (s), 939 (w), 907 (w), 869 (w), 837 (w),
781 (w), 754 (m), 720 (w), 703 (w), 652 (w), 606 (w), 588 (w), 537
(w) cm–1. HRMS (FAB): calcd. for C19H23NNaO5 [M + Na]+
368.1474; found 368.1464.
ν = 2976 (br), 1686 (s), 1650 (m), 1566 (s), 1489 (w), 1452 (w), 1410 Diethyl 1-[(Methoxycarbonyl)methyl]-4-phenyl-1,4-dihydropyridine-
˜
(m), 1389 (w), 1365 (m), 1302 (m), 1280 (m), 1246 (w), 1223 (m),
1172 (s), 1146 (s), 1091 (m), 1070 (s), 1027 (m), 977 (w), 955 (w),
3,5-dicarboxylate (4ax): Orange solid (73 mg, 39%). 1H NMR
(500 MHz, CDCl3): δ = 1.17 (t, J = 7.4 Hz, 6 H), 3.82 (s, 3 H),
911 (m), 839 (m), 828 (m), 753 (m), 719 (m), 703 (s), 681 (m), 4.00–4.11 (m, 4 H), 4.14 (s, 2 H), 4.86 (s, 1 H), 7.12 (s, 2 H), 7.13
664 (w), 625 (w), 602 (w), 543 (w) cm–1. HRMS (FAB): calcd. for (t, J = 7.4 Hz, 1 H), 7.24 (dd, J = 7.4, 6.8 Hz, 1 H), 7.40 (d, J =
C34H29NNaO4 [M + Na]+ 538.1989; found 538.1990.
6.8 Hz, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 14.1, 37.2,
52.7, 55.0, 60.1, 109.7, 126.4, 127.8, 128.4, 137.3, 146.3, 166.7,
Diethyl 1-Methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarb-
oxylate (4at): Yellow oil (116 mg, 64%). 1H NMR (500 MHz,
CDCl3): δ = 1.16 (t, J = 7.1 Hz, 6 H), 3.28 (s, 3 H), 4.00–4.09 (m,
4 H), 4.99 (s, 1 H), 7.21 (s, 2 H), 7.38 (dd, J = 7.9, 7.4 Hz, 1 H),
7.67 (d, J = 7.9 Hz, 1 H), 7.99 (dd, J = 7.4, 2.3 Hz, 1 H), 8.10 (t,
J = 2.3 Hz, 1 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 14.0,
37.1, 41.5, 60.0, 107.4, 121.4, 123.0, 128.5, 134.5, 138.7, 148.1,
168.8 ppm. IR (neat): ν = 3066 (w), 2982 (w), 2949 (w), 1750 (m),
˜
1701 (m), 1678 (m), 1574 (m), 1490 (w), 1454 (w), 1437 (w), 1425
(w), 1414 (w), 1387 (w), 1364 (m), 1305 (m), 1242 (w), 1179 (s),
1083 (w), 1030 (w), 1120 (w), 1000 (w), 986 (w), 943 (w), 924 (w),
864 (w), 839 (w), 825 (w), 755 (m), 718 (w), 698 (m), 656 (w), 609
(w), 602 (w) cm–1. HRMS (FAB): calcd. for C20H24NO6 [M + H]+
374.1604; found 374.1591.
148.7, 166.2 ppm. IR (KBr): ν = 3432 (br), 2985 (w), 2937 (w),
˜
2904 (w), 2366 (w), 1700 (s), 1633 (w), 1579 (m), 1529 (s), 1475 (w),
1444 (w), 1369 (m), 1348 (m), 1280 (m), 1214 (s), 1189 (w), 1095
Diethyl 1-[(S)-1-(Methoxycarbonyl)ethyl]-4-phenyl-1,4-dihydropyr-
idine-3,5-dicarboxylate (4ay): Yellow oil (114 mg, 59%). [α]1D9
=
(w), 1070 (s), 1027 (w), 927 (w), 829 (w), 809 (w), 761 (m), 721 (w), –12.9 (c = 0.01, CHCl3, 84% ee). The ee was determined by HPLC
686 (w) cm–1. HRMS (FAB): calcd. for C18H21N2O6 [M
H]+ 361.1400; found 361.1417.
+
analysis using a chiral column (CHIRALPAK AD-H, hexane/2-
propanol = 9:1, flow rate: 1.0 mL/min, detection at 254 nm, room
5292
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© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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1,4-Dihydropyridines and Their Fluorescence Properties
1
temp.): tR = 15.8 (major), 19.0 min (minor). H NMR (500 MHz,
109.1, 114.5, 127.8, 128.1, 128.7, 137.4, 144.5, 159.6, 167.1 ppm.
CDCl3): δ = 1.11 (td, J = 7.4, 2.3 Hz, 6 H), 1.59 (d, J = 7.4 Hz, 3 IR (KBr): ν = 2977 (w), 2937 (w), 2902 (w), 2838 (w), 1698 (s),
˜
H), 3.74 (s, 3 H), 3.94–4.07 (m, 4 H), 4.15 (d, J = 7.4 Hz, 1 H),
4.81 (s, 1 H), 7.04–7.07 (m, 1 H), 7.14–7.19 (m, 4 H), 7.25–7.27 (m,
2 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 14.1, 16.6, 37.7, 52.9,
60.1, 60.7, 109.7, 109.7, 126.3, 127.8, 128.3, 135.4, 135.9, 146.3,
1681 (s), 1614 (w), 1579 (s), 1513 (m), 1417 (w), 1367 (w), 1307
(m), 1282 (w), 1251 (m), 1234 (m), 1174 (s), 1083 (w), 1033 (w),
908 (w), 817 (w) cm–1. HRMS (FAB): calcd. for C44H48N2O10
[M]+ 764.3309; found 764.3319.
166.8, 171.0 ppm. IR (neat): ν = 2981 (w), 1743 (m), 1695 (s), 1583
˜
Tetraethyl 4,4Ј-(1,3-Phenylene)bis[1-(naphthalen-2-ylmethyl)-1,4-di-
hydropyridine-3,5-dicarboxylate] (4bc): Yellow oil (242 mg, 60%).
1H NMR (500 MHz, CDCl3): δ = 1.04 (t, J = 7.4 Hz, 12 H), 3.92–
4.01 (m, 8 H), 4.87 (s, 2 H), 5.02 (s, 4 H), 6.97–7.04 (m, 3 H), 7.30
(s, 4 H), 7.30–7.31 (m, 1 H), 7.44 (d, J = 6.8 Hz, 2 H), 7.51 (dd, J
= 7.4, 8.2 Hz, 2 H), 7.56 (dd, J = 6.8, 7.9 Hz, 2 H), 7.62 (dd, J =
7.4, 8.2 Hz, 2 H), 7.86 (d, J = 7.9 Hz, 2 H), 7.91 (d, J = 8.2 Hz, 4
H) ppm. 13C NMR(125 MHz, CDCl3): δ = 14.1, 37.5, 56.0, 59.9,
109.4, 122.5, 125.5, 126.1 126.3, 126.6, 127.0, 127.5, 128.2, 129.1,
(m), 1491 (w), 1453 (w), 1420 (w), 1371 (m), 1277 (m), 1169 (s),
1032 (m), 973 (w), 899 (w), 836 (w), 752 (m), 718 (w), 698 (m), 609
(w) cm–1. HRMS (FAB): calcd. for C21H26NO6 [M + H]+ 388.1760;
found 388.1771.
Diethyl 1-[(S)-1-(Methoxycarbonyl)-2-phenylethyl]-4-phenyl-1,4-di-
hydropyridine-3,5-dicarboxylate (4az): Orange-yellow oil (116 mg,
50%). [α]1D9 = –119 (c = 0.01, CHCl3, 77% ee). The ee was deter-
mined by HPLC analysis using a chiral column (CHIRALPAK
AD-H, hexane/2-propanol = 9:1, flow rate: 1.0 mL/min, detection
at 254 nm, room temp.): tR = 18.6 (major), 21.3 min (minor). 1H
NMR (500 MHz, CDCl3): δ = 1.07 (t, J = 7.4 Hz, 3 H), 1.09 (t, J
= 7.4 Hz, 3 H), 3.10 (dd, J = 14.5, 11.1 Hz, 1 H), 3.38 (dd, J =
14.5, 5.1 Hz, 1 H), 3.74 (s, 3 H), 3.88–4.06 (m, 4 H), 4.25 (dd, J =
11.1, 5.1 Hz, 1 H), 4.72 (s, 1 H), 6.93–6.95 (m, 2 H), 7.00–7.09
(m, 4 H), 7.14–7.18 (m, 3 H), 7.22–7.30 (m, 3 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 14.1, 36.6, 37.7, 52.9, 60.0, 66.8, 109.2,
109.9, 126.1, 127.3, 127.7, 128.3, 128.9, 129.0, 135.1, 135.3, 137.0,
129.2, 130.8, 131.1, 133.9, 137.4, 146.0, 167.0 ppm. IR (KBr): ν =
˜
2981 (w), 2935 (w), 2902 (w), 2873 (w), 1700 (s), 1579 (m), 1511
(w), 1415 (w), 1371 (w), 1307 (w), 1278 (w), 1230 (w), 1193 (s),
1157 (w), 1078 (m), 1024 (m), 792 (w), 757 (m) cm–1. HRMS
(FAB): calcd. for C50H48N2O8 [M]+ 804.3411; found 804.3395.
Tetraethyl 4,4Ј-(Biphenyl-4,4Ј-diyl)bis(1-benzyl-1,4-dihydropyridine-
3,5-dicarboxylate) (4bd): Yellow solid (71 mg, 61 %). 1H NMR
(500 MHz, CDCl3): δ = 1.18 (t, J = 7.4 Hz, 12 H), 4.01–4.13 (m, 8
H), 4.60 (s, 4 H), 4.93 (s, 2 H), 7.29–7.30 (m, 12 H), 7.35–7.43 (m,
10 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 14.2, 37.0, 58.3,
60.1, 109.1, 126.6, 127.2, 128.4, 128.5, 129.2, 136.2, 137.6, 145.3,
146.3, 166.6, 170.0 ppm. IR (neat): ν = 2980 (w), 1741 (m), 1696
˜
(s), 1584 (s), 1492 (w), 1421 (w), 1371 (m), 1278 (m), 1166 (s), 1073
(s), 1023 (w), 899 (w), 837 (w), 751 (m), 718 (w), 697 (m), 596
(w), 567 (w) cm–1. HRMS (FAB): calcd. for C27H30NO6 [M + H]+
464.2073; found 464.2079,
167.0 ppm. IR (neat): ν = 2978 (br), 2929 (br), 2360 (w), 2341 (w),
˜
1694 (s), 1578 (m), 1495 (w), 1454 (w), 1389 (w), 1369 (m), 1303
(w), 1276 (m), 1226 (m), 1164 (s), 1071 (s), 1020 (m), 975 (m), 904
(m), 838 (m), 817 (m), 732 (m), 698 (m), 618 (w), 578 (w) cm–1.
HRMS (FAB): calcd. for C48H47N2O8 [M – H]+ 779.3332; found
779.3332.
Diethyl
1-Benzyl-4-{4-[1-benzyl-3,5-bis(ethoxycarbonyl)-1,4-di-
hydropyridin-4-yl]phenyl}-1,4-dihydropyridine-3,5-dicarboxylate (4ba):
Yellow solid (169 mg, 48%). 1H NMR (500 MHz, CDCl3): δ = 1.12
(t, J = 7.4 Hz, 12 H), 3.96–4.08 (m, 8 H), 4.55 (s, 4 H), 4.84 (s, 2
H), 7.12 (s, 4 H), 7.24 (s, 4 H), 7.26 (d, J = 6.8 Hz, 4 H), 7.34 (t,
J = 7.4 Hz, 2 H), 7.39 (dd, J = 7.4, 6.8 Hz, 4 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 14.1, 36.8, 58.1, 59.8, 109.1, 127.1, 127.8,
Tetraethyl 1,1Ј-(Propane-1,3-diyl)bis(4-phenyl-1,4-dihydropyridine-
3,5-dicarboxylate) (4be): Yellow solid (83 mg, 49 %). 1H NMR
(500 MHz, CDCl3): δ = 1.18 (t, J = 6.8 Hz, 12 H), 2.10–2.16 (tt, J
= 7.4, 7.4 Hz, 2 H), 3.50 (t, J = 7.4 Hz, 4 H), 4.01–4.14 (m, 8 H),
4.91 (s, 2 H), 7.19 (s, 4 H), 7.25–7.31 (m, 10 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 14.2, 30.9, 37.2, 51.8, 60.2, 109.4, 126.5,
128.2, 129.0, 136.2, 137.4, 144.4, 166.9 ppm. IR (neat): ν = 2980
˜
(w), 1693 (s), 1655 (w), 1615 (w), 1576 (m), 1497 (w), 1475 (w),
1445 (w), 1417 (w), 1386 (w), 1364 (w), 1304 (w), 1277 (m), 1221
(m), 1203 (w), 1159 (s), 1092 (w), 1068 (m), 963 (w), 928 (w), 902
(w), 864 (w), 819 (w), 805 (w), 748 (w), 739 (w), 721 (w), 701 (m),
639 (w), 602 (w), 573 (w) cm–1. HRMS (ESI): calcd. for
C42H44N2NaO8 [M + Na]+ 727.2995; found 727.2987.
128.0, 128.1, 136.8, 146.3, 166.8 ppm. IR (KBr): ν = 2976 (br),
˜
1693 (s), 1577 (m), 1490 (w), 1453 (w), 1412 (w), 1370 (m), 1306
(w), 1276 (m), 1167 (s), 1066 (s), 1029 (s), 900 (m), 859 (w), 837
(m), 751 (s), 717 (m), 697 (s), 601 (w) cm–1. HRMS (FAB): calcd.
for C37H41N2O8 [M – H]+ 641.2863; found 641.2874.
Diethyl 1-Benzyl-4-(4-formylphenyl)-1,4-dihydropyridine-3,5-dicarb-
oxylate (4baЈ): Yellow oil (28 mg, 13%). 1H NMR (500 MHz,
CDCl3): δ = 1.09 (t, J = 7.4 Hz, 6 H), 3.93–4.07 (m, 4 H), 4.53 (s,
2 H), 4.93 (s, 1 H), 7.19–7.38 (m, 4 H), 7.29–7.38 (m, 5 H), 7.67
(d, J = 8.5 Hz, 2 H), 9.87 (s, 1 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 14.2, 37.9, 58.4, 60.2, 108.3, 127.2, 128.5, 129.0, 129.2,
Tetraethyl 1,1Ј-(Propane-1,3-diyl)bis[4-(3-nitrophenyl)-1,4-di-
hydropyridine-3,5-dicarboxylate] (4bf): Yellow solid (146 mg, 80%).
1H NMR (500 MHz, CDCl3): δ = 1.16 (t, J = 6.8 Hz, 12 H), 2.20–
2.26 (tt, J = 7.4, 7.4 Hz, 2 H), 3.64 (t, J = 7.4 Hz, 4 H), 4.00–4.13
(m, 8 H), 5.04 (s, 2 H), 7.28 (s, 4 H), 7.45 (dd, J = 7.9, 7.9 Hz, 2
H), 7.73 (dt, J = 7.4, 1.1 Hz, 2 H), 8.04 (ddd, J = 7.9, 2.3, 1.1 Hz,
2 H), 8.13 (t, J = 2.3 Hz, 2 H) ppm. 13C NMR (125 MHz, CDCl3):
δ = 14.1, 30.5, 37.4, 51.8, 60.4, 108.6, 121.7, 123.0, 128.8, 134.5,
129.6, 134.8, 135.9, 138.0, 153.2, 166.5, 192.1 ppm. IR (neat): ν =
˜
2980 (br), 1692 (s), 1603 (m), 1578 (s), 1497 (w), 1454 (w), 1411
(w), 1389 (m), 1370 (m), 1304 (m), 1277 (m), 1227 (s), 1164 (s),
1073 (s), 1018 (s), 976 (m), 908 (m), 806 (m), 770 (m), 731 (s),
699 (m), 646 (m), 619 (m), 575 (w) cm–1. HRMS (FAB): calcd. for
C25H25NNaO5 [M + Na]+ 442.1625; found 442.1625.
137.4, 148.4, 148.5, 166.1 ppm. IR (neat): ν = 2980 (br), 1692 (s),
˜
1578 (m), 1524 (s), 1461 (w), 1413 (w), 1371 (m), 1345 (m), 1277
(m), 1166 (s), 1067 (s), 1028 (m), 926 (w), 885 (w), 828 (w), 806
(w), 759 (s), 740 (m), 720 (m), 683 (m) cm–1. HRMS (FAB): calcd.
for C37H39N4O12 [M – H]+ 731.2564; found 731.2579.
Diethyl 4-{4-[3,5-Bis(ethoxycarbonyl)-1-(4-methoxybenzyl)-1,4-di-
hydropyridin-4-yl]phenyl}-1-(4-methoxybenzyl)-1,4-dihydropyridine- Diethyl 4-Phenyl-1,4-dihydropyridine-3,5-dicarboxylate (4ca): Red-
1
3,5-dicarboxylate (4bb): Yellow solid (131 mg, 34 %). 1H NMR
brown oil (83 mg, 55%). H NMR (500 MHz, CDCl3): δ = 1.19 (t,
(500 MHz, CDCl3): δ = 1.13 (t, J = 7.1 Hz, 12 H), 3.82 (s, 6 H), J = 7.0 Hz, 6 H), 4.00–4.13 (m, 4 H), 4.89 (s, 1 H), 6.56 (br. s, 1
3.97–4.08 (m, 8 H), 4.49 (s, 4 H), 4.82 (s, 2 H), 6.93 (d, J = 8.5 Hz, H), 7.15 (t, J = 7.4 Hz, 1 H), 7.26 (dd, J = 7.4, 7.4 Hz, 2 H), 7.30
4 H), 7.09 (s, 4 H), 7.20 (d, J = 8.5 Hz, 4 H), 7.22 (s, 4 H) ppm.
(d, J = 5.1 Hz, 2 H), 7.35 (d, J = 7.4 Hz, 2 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 14.2, 37.6, 60.0, 108.5, 126.4, 127.9, 128.3,
13C NMR (125 MHz, CDCl3): δ = 14.1, 36.9, 55.3, 57.8, 59.9,
Eur. J. Org. Chem. 2014, 5281–5301
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5293

S. Sueki, I. Shimizu et al.
FULL PAPER
133.6, 146.9, 167.1 ppm. IR (neat): ν = 3321 (br), 2980 (w), 1686 (m), 1177 (s), 1068 (s), 1037 (m), 1021 (m), 908 (m), 841 (w), 830
˜
(m), 1601 (m), 1474 (m), 1392 (w), 1370 (m), 1285 (m), 1242 (w),
1177 (s), 1064 (s), 1019 (w), 911 (w), 843 (w), 828 (w), 752 (m),
(w), 754 (m), 728 (s), 703 (m), 646 (m), 610 (w) cm–1. HRMS
(FAB): calcd. for C17H19ClNO4 [M + H]+ 336.1003; found
709 (w), 696 (m), 646 (w), 609 (w) cm–1. HRMS (FAB): calcd. for 336.0997.
C17H19NNaO4 [M + Na]+ 324.1205; found 324.1206.
Diethyl 4-(3-Chlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
1
Diethyl 4-(4-Methoxyphenyl)-1,4-dihydropyridine-3,5-dicarboxylate
(4cb): Orange oil (94 mg, 57%). H NMR (500 MHz, CDCl3): δ =
1.20 (t, J = 7.0 Hz, 6 H), 3.75 (s, 3 H), 4.01–4.14 (m, 4 H), 4.84 (s,
1 H), 6.70 (br. s, 1 H), 6.78 (d, J = 9.1 Hz, 2 H), 7.25 (d, J = 9.1 Hz,
2 H), 7.29 (d, J = 5.5 Hz, 2 H) ppm. 13C NMR (125 MHz, CDCl3):
δ = 14.2, 36.7, 55.1, 59.9, 108.6, 129.2, 133.4, 139.5, 158.1,
(4cg): Yellow solid (79 mg, 47%). H NMR (500 MHz, CDCl3): δ
1
= 1.20 (t, J = 6.8 Hz, 6 H), 4.02–4.16 (m, 4 H), 4.88 (s, 1 H), 6.86
(br. s, 1 H), 7.13 (d, J = 7.9 Hz, 1 H), 7.18 (dd, J = 7.9, 7.4 Hz, 1
H), 7.25 (d, J = 7.4 Hz, 1 H), 7.30 (s, 1 H), 7.33 (d, J = 5.1 Hz, 2
H) ppm. 13C NMR (125 MHz, CDCl3): δ = 14.1, 37.5, 60.2, 107.8,
126.6, 128.5, 129.1, 134.0, 148.8, 167.0 ppm. IR (neat): ν = 3301
˜
167.2 ppm. IR (neat): ν = 3321 (br), 2979 (w), 2836 (w), 1689 (m),
˜
(br), 2977 (w), 2905 (w), 1702 (m), 1665 (s), 1601 (m), 1572 (w),
1500 (m), 1473 (m), 1443 (w), 1429 (w), 1394 (w), 1370 (m), 1290
(m), 1239 (m), 1181 (s), 1118 (m), 1079 (m), 1060 (s), 1017 (m), 916
(m), 868 (m), 791 (m), 770 (s), 719 (m), 687 (m), 667 (m), 650 (m),
614 (m), 598 (m), 531 (w) cm–1. HRMS (FAB): calcd. for
C17H18ClNNaO4 [M + Na]+ 358.0816; found 358.0817.
1604 (m), 1506 (m), 1464 (m), 1392 (w), 1371 (m), 1286 (m), 1237
(m), 1172 (s), 1066 (s), 1032 (w), 909 (w), 849 (w), 825 (m), 787
(w), 738 (m), 705 (w), 647 (w), 624 (w), 573 (w) cm–1. HRMS
(FAB): calcd. for C18H21NNaO5 [M + Na]+ 354.1312; found
354.1311.
Diethyl 4-(4-Hydroxyphenyl)-1,4-dihydropyridine-3,5-dicarboxylate
(4cc): Yellow crystal (32 mg, 40 %). 1H NMR (500 MHz, [D6]-
DMSO): δ = 1.12 (t, J = 6.8 Hz, 6 H), 3.93–4.05 (m, 4 H), 4.60 (s,
1 H), 6.60 (d, J = 9.1 Hz, 2 H), 6.96 (d, J = 9.1 Hz, 2 H), 7.30 (d,
J = 2.8 Hz, 2 H), 9.07 (br. s, 1 H), 9.12 (s, 1 H) ppm. 13C NMR
(125 MHz, [D6]DMSO): δ = 14.2, 35.9, 59.2, 106.4, 114.6, 128.6,
Diethyl 4-(4-Chlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
(4ch): Yellow oil (73 mg, 44%). H NMR (500 MHz, CDCl3): δ =
1.25 (t, J = 7.4 Hz, 6 H), 4.07–4.19 (m, 4 H), 4.92 (s, 1 H), 6.92
(br. s, 1 H), 7.26 (d, J = 8.2 Hz, 2 H), 7.32 (d, J = 8.2 Hz, 2 H),
7.35 (d, J = 5.1 Hz, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ =
14.2, 37.1, 60.1, 107.9, 128.0, 129.6, 132.0, 133.8, 145.4, 167.0 ppm.
1
134.5, 138.2, 155.7, 166.5 ppm. IR (neat): ν = 3317 (m), 3096 (w),
˜
IR (neat): ν = 3320 (br), 2980 (w), 2359 (w), 2342 (w), 1697 (s),
˜
2964 (w), 1673 (m), 1650 (m), 1590 (w), 1495 (m), 1463 (w), 1450
(m), 1396 (m), 1377 (m), 1289 (m), 1249 (m), 1197 (s), 1169 (m),
1105 (m), 1096 (m), 1012 (m), 924 (w), 909 (m), 853 (m), 838 (m),
825 (m), 805 (m), 776 (w), 748 (m), 707 (m), 655 (m), 634 (m),
565 (m) cm–1. HRMS (FAB): calcd. for C17H19NNaO5 [M + Na]+
340.1161; found 340.1149.
1603 (m), 1486 (s), 1392 (w), 1370 (m), 1284 (m), 1243 (w), 1180
(s), 1067 (s), 1014 (m), 1601 (m), 1474 (m), 1392 (w), 1370 (m),
1284 (m), 1243 (w), 1180 (s), 1067 (s), 1014 (m), 910 (w), 844 (w),
821 (w), 759 (w), 727 (w), 669 (w), 621 (w) cm–1. HRMS (FAB):
calcd. for C17H18ClNNaO4 [M + Na]+ 358.0817; found 358.0816.
General Procedure for the Synthesis of N-Protected 1,4-DHPs 4d:
A solution of 1,4-DHP 4ca (1.2 mmol, 1.0 equiv.) in THF (6 mL)
was added dropwise to a suspension of NaH (2.0 equiv.) in THF
(2 mL) at 0 °C. After the evolution of H2 gas was complete, the
protecting reagent (1.5 equiv.) was added to the reaction mixture.
The solution was warmed to ambient temperature and stirred for
24 h and the resulting mixture was acidified by using satd. aq.
NH4Cl. The aqueous layer was extracted with CH2Cl2 (3ϫ 15 mL),
dried with MgSO4, filtered, and the solvents evaporated. Removal
of the solvent in vacuo followed by column chromatography on
silica gel (AcOEt/n-hexane) afforded N-protected 1,4-DHPs 4d.
Diethyl 4-(3-Nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
(4cd): Yellow oil (89 mg, 51%). H NMR (500 MHz, CDCl3): δ =
1
1.20 (t, J = 6.8 Hz, 6 H), 4.02–4.15 (m, 4 H), 5.04 (s, 1 H), 6.94
(br. s, 1 H), 7.41 (d, J = 5.7 Hz, 2 H), 7.43 (dd, J = 7.9, 7.4 Hz, 1
H), 7.74 (d, J = 7.4 Hz, 1 H), 8.03 (d, J = 7.9 Hz, 1 H), 8.18 (s, 1
H) ppm. 13C NMR (125 MHz, CDCl3): δ = 14.1, 37.8, 60.3, 107.5,
121.6, 123.2, 128.6, 134.3, 134.8, 148.3, 149.0, 166.7 ppm. IR
(neat): ν = 3322 (br), 3103 (w), 2981 (w), 1686 (m), 1602 (w), 1525
˜
(m), 1473 (m), 1392 (w), 1372 (m), 1348 (m), 1286 (m), 1243 (w),
1178 (s), 1065 (s), 1018 (m), 915 (w), 885 (w), 826 (w), 806 (w), 760
(m),739 (m), 712 (m), 675 (m), 645 (w), 610 (w) cm–1. HRMS
(FAB): calcd. for C17H19N2O6 [M + H]+ 347.1243; found 347.1246.
Diethyl 1-Benzoyl-4-phenyl-1,4-dihydropyridine-3,5-dicarboxylate
1
(4da): Colorless oil (349 mg, 74%). H NMR (500 MHz, CDCl3):
Diethyl 4-(4-Nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
1
δ = 1.16 (t, J = 6.8 Hz, 6 H), 4.03–4.16 (m, 4 H), 4.96 (s, 1 H), 7.20
(t, J = 7.4 Hz, 1 H), 7.29 (t, J = 7.4 Hz, 2 H), 7.36 (d, J = 7.9 Hz,
2 H), 7.51 (t, J = 7.4 Hz, 2 H), 7.59 (t, J = 7.4 Hz, 1 H), 7.66 (d,
J = 8.5 Hz, 2 H), 8.11 (s, 2 H) ppm. 13C NMR (125 MHz, CDCl3):
δ = 14.0, 38.8, 60.7, 115.5, 127.0, 128.2, 128.4, 128.9, 129.0, 131.1,
(4ce): Yellow oil (113 mg, 67%). H NMR (500 MHz, CDCl3): δ =
1.19 (t, J = 7.0 Hz, 6 H), 4.02–4.16 (m, 4 H), 5.04 (s, 1 H), 6.78
(br. s, 1 H), 7.38 (d, J = 5.8 Hz, 2 H), 7.52 (d, J = 8.5 Hz, 2 H),
8.12 (d, J = 8.5 Hz, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ =
14.2, 38.0, 60.3, 107.5, 123.3, 129.2, 134.2, 146.5, 154.0, 166.5 ppm.
131.7, 132.6, 143.6, 165.6, 167.9 ppm. IR (neat): ν = 3062 (w), 2984
˜
IR (neat): ν = 3324 (br), 2981 (w), 1693 (m), 1604 (m), 1516 (m),
˜
(w), 1713 (m), 1692 (s), 1662 (m), 1614 (m), 1599 (m), 1578 (w),
1491 (w), 1477 (w), 1446 (w), 1377 (m), 1347 (m), 1224 (s), 1145
(m), 1114 (m), 1075 (s), 1016 (m), 962 (m), 933 (m), 899 (m), 870
(m), 837 (m), 789 (m), 777 (w), 751 (m), 713 (s), 697 (s), 667 (m),
643 (m), 622 (m), 564 (w) cm–1. HRMS (FAB): calcd. for
C24H23NNaO5 [M + Na]+ 428.1474; found 428.1485.
1475 (m), 1392 (w), 1370 (w), 1343 (s), 1285 (m), 1241 (w), 1180
(s), 1108 (w), 1068 (s), 1015 (w), 912 (w), 826 (w), 754 (w), 714 (m),
647 (w) cm–1. HRMS (FAB): calcd. for C17H18N2NaO6 [M +
Na]+ 369.1057; found 369.1057.
Diethyl 4-(2-Chlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
1
(4cf): Yellow solid (79 mg, 47%). H NMR (500 MHz, CDCl3): δ
= 1.17 (t, J = 6.8 Hz, 6 H), 4.01–4.12 (m, 4 H), 5.37 (s, 1 H), 6.77
(br. s, 1 H), 7.07 (t, J = 7.4 Hz, 1 H), 7.17 (dd, J = 7.9, 7.4 Hz, 1
H), 7.27 (dd, J = 7.9, 7.4 Hz, 1 H), 7.33 (d, J = 5.1 Hz, 2 H), 7.38
(d, J = 7.9 Hz, 1 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 14.1,
34.9, 60.1, 108.2, 126.8, 127.5, 129.1, 131.6, 132.7, 134.3, 144.9,
1-Allyl 3,5-Diethyl 4-Phenylpyridine-1,3,5(4H)-tricarboxylate (4db):
Colorless oil (213 mg, 57%). 1H NMR (500 MHz, CDCl3): δ = 1.20
(t, J = 6.8 Hz, 6 H), 4.05–4.17 (m, 4 H), 4.85 (d, J = 6.2 Hz, 2 H),
4.87 (s, 1 H), 5.36 (dd, J = 1.1, 10.2 Hz, 1 H), 5.44 (dd, J = 1.1,
17.0 Hz, 1 H), 6.02 (ddt, J = 6.2, 10.2, 17.0 Hz, 1 H), 7.16 (dd, J
= 7.9, 7.4 Hz, 1 H), 7.24 (t, J = 7.4 Hz, 2 H), 7.28 (d, J = 7.9 Hz,
2 H), 8.04 (s, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 14.0,
167.1 ppm. IR (neat): ν = 3323 (br), 3106 (w), 2980 (w), 1681 (m),
˜
1600 (m), 1471 (m), 1440 (m), 1392 (w), 1370 (m), 1289 (m), 1245
5294
www.eurjoc.org
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 5281–5301

1,4-Dihydropyridines and Their Fluorescence Properties
38.2, 60.6, 68.6, 115.0, 120.0, 126.8, 128.1, 128.6, 130.0, 130.9,
1-(4-Methoxybenzyl)-4-phenyl-1,4-dihydropyridine-3,5-dicarbonitrile
(4ec): Yellow solid (42 mg, 26%). H NMR (500 MHz, CDCl3): δ
1
143.8, 150.5, 165.7 ppm. IR (neat): ν = 2981 (w), 1744 (m), 1709
˜
(s), 1674 (m), 1617 (m), 1492 (w), 1454 (w), 1380 (m), 1366 (m),
= 3.85 (s, 3 H), 4.39 (s, 1 H), 4.40 (s, 2 H), 6.66 (s, 2 H), 6.95 (d, J
1346 (m), 1264 (m), 1210 (s), 1076 (m), 1019 (m), 977 (m), 901 (m), = 8.5 Hz, 2 H), 7.15 (d, J = 8.5 Hz, 2 H), 7.27 (d, J = 7.4 Hz, 2
862 (m), 840 (m), 750 (m), 715 (m), 697 (m), 544 (w) cm–1. HRMS H), 7.32 (t, J = 7.4 Hz, 1 H), 7.39 (dd, J = 7.4, 7.4 Hz, 2 H) ppm.
(FAB): calcd. for C21H23NNaO6 [M + Na]+ 408.1423; found
408.1426.
13C NMR (125 MHz, CDCl3): δ = 40.5, 55.4, 57.9, 88.9, 114.9,
118.2, 126.0, 127.8, 128.4, 129.1, 129.2, 139.0, 141.5, 160.2 ppm.
IR (neat): ν = 3070 (w), 2933 (w), 2837 (w), 2359 (w), 2204 (m),
˜
Diethyl 1-(tert-Butyldimethylsilyl)-4-phenyl-1,4-dihydropyridine-3,5-
dicarboxylate (4dc): Colorless oil (125 mg, 34 %). 1H NMR
(500 MHz, CDCl3): δ = 0.31 (s, 6 H), 0.91 (s, 9 H), 1.08 (t, J =
6.8 Hz, 6 H), 3.91–4.04 (m, 4 H), 4.77 (s, 1 H), 7.03 (t, J = 7.4 Hz,
1 H), 7.13 (dd, J = 7.9, 7.4 Hz, 2 H), 7.21 (d, J = 7.9 Hz, 2 H),
7.25 (s, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ = –6.0, 14.1,
18.7, 25.9, 37.4, 59.9, 110.3, 126.1, 127.7, 128.4, 137.0, 147.0,
1989 (w), 1668 (m), 1610 (m), 1578 (s), 1535 (w), 1512 (s), 1454
(m), 1404 (s), 1355 (m), 1304 (m), 1247 (s), 1210 (m), 1177 (m),
1128 (m), 1078 (w), 1028 (m), 971 (w), 893 (m), 818 (m), 755 (s),
699 (s), 672 (m), 639 (m), 615 (m), 551 (m), 533 (m) cm–1. HRMS
(FAB): calcd. for C21H17N3NaO [M + Na]+ 350.1269; found
350.1264.
4-Phenyl-1,4-dihydropyridine-3,5-dicarbonitrile (4ed): Yellow solid
(148 mg, 48%). 1H NMR (500 MHz, [D6]DMSO): δ = 4.55 (s, 1
H), 7.25 (s, 2 H), 7.37 (d, J = 6.8 Hz, 2 H), 7.39 (dd, J = 7.4,
6.8 Hz, 1 H), 7.49 (t, J = 7.4 Hz, 2 H), 9.62 (br. s, 1 H) ppm. 13C
NMR (125 MHz, [D6]DMSO): δ = 39.4, 85.4, 119.3, 127.8, 127.8,
167.3 ppm. IR (neat): ν = 2932 (w), 2903 (w), 2860 (w), 1697 (m),
˜
1655 (w), 1613 (m), 1581 (m), 1494 (w), 1471 (w), 1365 (w), 1312
(m), 1284 (m), 1255 (m), 1211 (s), 1186 (s), 1073 (s), 1041 (s), 1002
(m), 921 (m), 886 (m), 859 (m), 835 (m), 809 (s), 772 (m), 753 (m),
719 (m), 701 (m), 680 (m), 638 (w), 590 (m), 536 (w) cm–1. HRMS
(FAB): calcd. for C23H33NNaO4Si [M + Na]+ 438.2077; found
438.2079.
128.9, 137.6, 143.6 ppm. IR (neat): ν = 3327 (br), 3085 (w), 2208
˜
(s), 2185 (w), 1672 (m), 1647 (w), 1602 (m), 1466 (s), 1354 (w), 1340
(w), 1275 (m), 1251 (w), 1223 (w), 1211 (w), 1159 (w), 1135 (w),
1075 (m), 1029 (w), 906 (m), 851 (w), 824 (w), 753 (m), 669 (s), 671
(m), 642 (s), 616 (m) cm–1. HRMS (FAB): calcd. for C13H10N3 [M
+ H]+ 208.0875; found 208.0872.
Diethyl 4-Phenyl-1-(p-tosyl)-1,4-dihydropyridine-3,5-dicarboxylate
1
(4dd): White solid (228 mg, 60%). H NMR (500 MHz, CDCl3): δ
= 1.18 (t, J = 6.8 Hz, 6 H), 2.50 (s, 3 H), 4.02–4.15 (m, 4 H), 4.76
(s, 1 H), 6.88 (d, J = 7.9 Hz, 2 H), 7.06 (dd, J = 7.9, 7.4 Hz, 2 H),
7.08 (t, J = 7.4 Hz, 1 H), 7.42 (d, J = 8.5 Hz, 2 H), 7.78 (s, 2 H),
7.81 (d, J = 8.5 Hz, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ =
14.0, 21.7, 37.9, 60.8, 115.6, 126.8, 127.2, 127.9, 128.3, 129.4, 130.5,
1-(4-Methoxyphenyl)-3,5-dinitro-4-phenyl-1,4-dihydropyridine (4ee):
1
Red-brown solid (78 mg, 44%). H NMR (500 MHz, CDCl3): δ =
3.88 (s, 3 H), 5.72 (s, 1 H), 7.03 (d, J = 8.2 Hz, 2 H), 7.27–7.34 (m,
5 H), 7.41 (d, J = 8.2 Hz, 2 H), 8.13 (s, 2 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 39.7, 55.8, 115.5, 123.5, 128.2, 128.5, 128.6,
134.3, 143.4, 145.7, 165.2 ppm. IR (neat): ν = 3074 (w), 2973 (w),
˜
1698 (s), 1659 (w), 1606 (m), 1492 (w), 1466 (w), 1445 (w), 1383
(m), 1297 (m), 1271 (m), 1213 (m), 1188 (m), 1176 (s), 1137 (m),
1112 (m), 1083 (m), 1044 (s), 1015 (m), 927 (w), 901 (m), 888 (m),
864 (w), 841 (m), 818 (m), 799 (w), 776 (w), 759 (w), 749 (m), 738
(m), 716 (m), 701 (m), 661 (s), 644 (m), 617 (w), 570 (s), 543
(s) cm–1. HRMS (FAB): calcd. for C24H26NO6S [M + H]+
456.1481; found 456.1495.
134.1, 134.5, 134.5, 139.9, 159.8 ppm. IR (neat): ν = 3092 (w), 2930
˜
(w), 2838 (w), 1680 (m), 1605 (m), 1584 (w), 1507 (s), 1484 (s), 1457
(w), 1440 (w), 1386 (w), 1338 (m), 1305 (m), 1255 (s), 1215 (s), 1180
(s), 1119 (w), 1070 (m), 1023 (m), 963 (w), 927 (w), 915 (m), 897
(w), 876 (w), 849 (w), 839 (m), 827 (w), 809 (w), 775 (m), 747 (w),
732 (s), 713 (w), 701 (m), 641 (w), 629 (w), 581 (w), 535 (m) cm–1.
HRMS (FAB): calcd. for C18H16N3O5 [M + H]+ 354.1090; found
354.1093.
1-(4-Methoxyphenyl)-4-phenyl-1,4-dihydropyridine-3,5-dicarbo-
nitrile (4ea): White-yellow solid (52 mg, 33%). 1H NMR (500 MHz,
CDCl3): δ = 3.84 (s, 3 H), 4.48 (s, 1 H), 6.95 (d, J = 9.1 Hz, 2 H),
6.96 (s, 2 H), 7.11 (d, J = 9.1 Hz, 2 H), 7.36–7.39 (m, 3 H), 7.43–
7.46 (m, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 40.5, 55.7,
90.1, 115.3, 118.0, 123.0, 127.9, 128.6, 129.3, 135.1, 138.4, 141.2,
1-(4-Fluorophenyl)-3,5-dinitro-4-phenyl-1,4-dihydropyridine (4ef):
1
Brown solid (64 mg, 38%). H NMR (500 MHz, CDCl3): δ = 5.71
(s, 1 H), 7.23–7.28 (m, 3 H), 7.31–7.34 (m, 2 H), 7.38–7.41 (m, 4
H), 8.13 (s, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 39.7,
3
2
117.5, 117.7, 124.0 (d, JCF = 9.5 Hz), 128.4 (d, JCF = 19.1 Hz),
128.7, 133.5, 134.85, 137.6 (d, 4JCF = 2.4 Hz), 139.7, 162.1 (d, 1JCF
159.0 ppm. IR (neat): ν = 2205 (s), 1670 (m), 1595 (w), 1578 (m),
˜
1511 (s), 1466 (w), 1454 (w), 1440 (w), 1431 (w), 1340 (m), 1305
(w), 1292 (m), 1253 (s), 1172 (m), 1137 (w), 1119 (w), 1069 (m),
1024 (m), 896 (m), 836 (m), 810 (m), 762 (s), 702 (s), 664 (m), 650
(w), 584 (m), 533 (m) cm–1. HRMS (FAB): calcd. for C20H16N3O
[M + H]+ 314.1293; found 314.1296.
= 250.3 Hz) ppm. IR (neat): ν = 3092 (br), 1676 (m), 1616 (w),
˜
1595 (w), 1553 (w), 1491 (s), 1381 (w), 1333 (m), 1294 (m), 1256
(s), 1221 (s), 1158 (m), 1113 (m), 1068 (m), 1013 (w), 906 (m), 896
(m), 828 (s), 782 (m), 732 (s), 701 (m), 644 (w), 575 (w) cm–1
.
HRMS (FAB): calcd. for C17H13FN3O4 [M + H]+ 342.0890; found
342.0902.
1,4-Bis(4-methoxyphenyl)-1,4-dihydropyridine-3,5-dicarbonitrile
1
(4eb): Yellow solid (52 mg, 30%). H NMR (500 MHz, CDCl3): δ
1-Mesityl-3,5-dinitro-4-phenyl-1,4-dihydropyridine (4eg): Yellow so-
1
= 3.82 (s, 3 H), 3.83 (s, 3 H), 4.42 (s, 1 H), 6.94–6.96 (m, 6 H), 7.10 lid (86 mg, 47%). H NMR (500 MHz, CDCl3): δ = 2.25 (s, 3 H),
(d, J = 8.5 Hz, 2 H), 7.28 (d, J = 8.5 Hz, 2 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 39.7, 55.3, 55.6, 90.3, 114.6, 115.3, 118.1,
2.36 (s, 3 H), 2.41 (s, 3 H), 5.78 (s, 1 H), 7.03 (s, 1 H), 7.04 (s, 1
H), 7.27 (t, J = 7.5 Hz, 1 H), 7.35 (dd, J = 10.0, 7.5 Hz, 2 H), 7.48
(d, J = 10.0 Hz, 2 H), 7.77 (s, 2 H) ppm. 13C NMR (125 MHz,
123.0, 129.1, 133.8, 135.1, 138.1, 159.0, 159.7 ppm. IR (neat): ν =
˜
3088 (w), 2955 (w), 2918 (w), 2836 (w), 2359 (w), 2206 (m), 2031 CDCl3): δ = 17.8, 18.2, 21.0, 39.9, 128.2, 128.6, 128.7, 130.0, 130.3,
(w), 1668 (m), 1610 (m), 1575 (m), 1511 (s), 1460 (m), 1444 (m), 133.8, 134.7, 135.5, 140.1, 140.4 ppm. IR (neat): ν = 3108 (w), 2920
˜
1425 (w), 1343 (m), 1305 (m), 1291 (m), 1250 (s), 1240 (s), 1194
(m), 1170 (s), 1145 (m), 1111 (m), 1068 (m), 1030 (m), 967 (w), 931
(m), 906 (m), 824 (s), 806 (m), 781 (m), 712 (w), 643 (m), 623 (m),
579 (m), 529 (m) cm–1. HRMS (FAB): calcd. for C21H17N3NaO2
[M + Na]+ 366.1218; found 366.1213.
(w), 1736 (w), 1674 (m), 1596 (m), 1485 (s), 1374 (w), 1334 (m),
1250 (s), 1227 (s), 1111 (m), 1063 (m), 908 (m), 890 (m), 859 (m),
829 (m), 775 (m), 735 (m), 722 (s), 697 (m), 648 (w), 590 (w), 570
(m) cm–1. HRMS (FAB): calcd. for C20H19NaN3O4 [M + Na]+
388.1273; found 388.1258.
Eur. J. Org. Chem. 2014, 5281–5301
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5295

S. Sueki, I. Shimizu et al.
FULL PAPER
1,4-Bis(4-methoxyphenyl)-3,5-dinitro-1,4-dihydropyridine (4eh): 1593 (m), 1566 (m), 1509 (s), 1452 (m), 1439 (m), 1427 (m), 1389
Orange solid (71 mg, 37%). 1H NMR (500 MHz, CDCl3): δ = 3.78 (w), 1372 (w), 1331 (m), 1294 (m), 1239 (s), 1210 (s), 1178 (s), 1117
(s, 3 H), 3.88 (s, 3 H), 5.67 (s, 1 H), 6.85 (d, J = 8.5 Hz, 2 H), 7.04
(d, J = 8.5 Hz, 2 H), 7.31 (d, J = 8.8 Hz, 2 H), 7.32 (d, J = 8.8 Hz,
2 H), 8.11 (s, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 38.9,
55.3, 55.8, 114.0, 115.5, 123.5, 129.6, 132.3, 133.8, 134.6, 134.6,
(m), 1089 (m), 1053 (m), 1028 (m), 969 (m), 936 (m), 922 (m), 879
(m), 842 (m), 828 (m), 804 (m), 773 (m), 751 (m), 718 (w), 693 (m),
673 (m), 648 (w), 613 (m), 569 (m), 556 (m), 534 (m) cm–1. HRMS
(FAB): calcd. for C22H21NNaO3 [M + Na]+ 370.1419; found
370.1402.
159.4, 159.7 ppm. IR (neat): ν = 3069 (w), 2968 (w), 1887 (w), 1670
˜
(m), 1607 (w), 1586 (w), 1509 (s), 1485 (s), 1462 (m), 1448 (w), 1342
(m), 1304 (m), 1247 (s), 1225 (s), 1171 (s), 1110 (m), 1069 (m), 1026
(m), 945 (m), 914 (m), 901 (m), 827 (s), 814 (m), 801 (m), 781 (m),
756 (m), 741 (m), 726 (m), 645 (m), 634 (m), 608 (m), 542 (s) cm–1.
HRMS (FAB): calcd. for C19H17N3NaO6 [M + Na]+ 406.1015;
found 406.1010.
1,1Ј-[4-(4-Chlorophenyl)-1-phenyl-1,4-dihydropyridine-3,5-diyl]di-
ethanone (4en): Yellow oil (375 mg, 38 %). H NMR (500 MHz,
1
CDCl3): δ = 2.21 (s, 6 H), 5.21 (s, 1 H), 7.19 (d, J = 8.5 Hz, 2 H),
7.30 (d, J = 8.5 Hz, 2 H), 7.35 (d, J = 8.5 Hz, 2 H), 7.39 (t, J =
7.4 Hz, 1 H), 7.52 (dd, J = 8.5, 7.4 Hz, 2 H), 7.55 (s, 2 H) ppm.
13C NMR (125 MHz, CDCl3): δ = 25.4, 35.2, 120.7, 121.5, 127.2,
128.3, 129.6, 130.2, 132.2, 136.7, 143.1, 143.9, 194.9 ppm. IR
3,5-Dinitro-1,4-diphenyl-1,4-dihydropyridine (4ei): Yellow solid
(50 mg, 31%). 1H NMR (500 MHz, CDCl3): δ = 5.64 (s, 1 H),
7.16–7.19 (m, 1 H), 7.23–7.26 (m, 2 H), 7.31–7.34 (m, 4 H), 7.37–
7.40 (m, 1 H), 7.42–7.50 (m, 2 H), 8.14 (s, 2 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 39.8, 121.5, 128.2, 128.5, 128.6, 128.6,
(neat): ν = 3070 (w), 1639 (s), 1593 (m), 1569 (m), 1493 (m), 1485
˜
(m), 1460 (w), 1428 (w), 1407 (w), 1341 (m), 1325 (m), 1303 (m),
1287 (m), 1237 (m), 1210 (s), 1085 (m), 1013 (m), 971 (m), 932 (m),
904 (w), 882 (m), 849 (w), 830 (w), 817 (w), 806 (m), 761 (m), 721
(w), 692 (s), 654 (w), 612 (m), 602 (m), 565 (m), 548 (m) cm–1.
HRMS (FAB): calcd. for C21H18ClNNaO2 [M + Na]+ 374.0924;
found 374.0917.
130.5, 133.5, 134.9, 139.8, 141.3 ppm. IR (neat): ν = 3055 (br), 1676
˜
(m), 1588 (m), 1489 (s), 1332 (m), 1256 (s), 1228 (s), 1112 (m), 1070
(m), 895 (m), 826 (w), 766 (m), 727 (s), 693 (s), 637 (w) cm–1
.
HRMS (FAB): calcd. for C17H14N3O4 [M + H]+ 324.0984; found
324.0996.
1,1Ј-[1-(4-Methoxybenzyl)-4-phenyl-1,4-dihydropyridine-3,5-diyl]di-
1
ethanone (4eo): Yellow solid (130 mg, 72%). H NMR (500 MHz,
1-(4-Methoxybenzyl)-3,5-dinitro-4-phenyl-1,4-dihydropyridine (4ej):
Orange solid (126 mg, 68%). 1H NMR (500 MHz, CDCl3): δ =
3.90 (s, 3 H), 4.70 (s, 2 H), 5.64 (s, 1 H), 6.99–7.00 (m, 2 H), 7.20–
7.25 (m, 2 H), 7.27–7.28 (m, 5 H), 7.88 (s, 2 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 39.7, 55.4, 58.9, 115.2, 125.3, 128.1, 128.4,
CDCl3): δ = 2.11 (s, 6 H), 3.84 (s, 3 H), 4.60 (s, 2 H), 5.18 (s, 1 H),
6.95 (d, J = 8.8 Hz, 2 H), 7.11 (t, J = 7.4 Hz, 1 H), 7.18 (s, 2 H),
7.19 (dd, J = 7.4, 7.4 Hz, 2 H), 7.22 (d, J = 8.8 Hz, 2 H), 7.26 (d,
J = 7.4 Hz, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 25.5,
35.7, 55.4, 58.1, 114.7, 119.4, 126.4, 127.5, 128.1, 128.2, 128.7,
128.5, 129.4, 133.7, 134.5, 140.1, 160.6 ppm. IR (neat): ν = 3096
˜
137.9, 145.7, 159.8 ppm. IR (neat): ν = 2960 (w), 1642 (m), 1625
˜
(w), 2916 (br), 1670 (m), 1584 (m), 1473 (m), 1383 (w), 1335 (w),
1244 (s), 1172 (s), 1114 (s), 1073 (m), 1026 (m), 918 (m), 885 (w),
830 (m), 694 (m), 659 (w), 633 (w), 599 (w), 562 (m) cm–1. HRMS
(FAB): calcd. for C19H18N3O5 [M + H]+ 368.1246; found 368.1234.
(m), 1610 (m), 1585 (w), 1562 (m), 1512 (m), 1491 (w), 1466 (w),
1411 (m), 1367 (m), 1330 (w), 1315 (w), 1304 (m), 1284 (m), 1247
(m), 1221 (m), 1169 (s), 1116 (m), 1088 (m), 1076 (m), 1023 (m),
954 (m), 939 (m), 884 (m), 873 (m), 850 (m), 839 (m), 817 (m), 753
(m), 721 (w), 698 (m), 677 (m), 642 (m), 603 (m), 569 (m), 553 (m),
533 (m) cm–1. HRMS (FAB): calcd. for C23H23NNaO3 [M + Na]+
384.1576; found 384.1564.
N,N-Dimethyl-4-[3,5-dinitro-4-phenylpyridin-1(4H)-yl]aniline (4ek):
Black crystal (73 mg, 40%). 1H NMR (500 MHz, CDCl3): δ = 3.03
(s, 6 H), 5.72 (s, 1 H), 6.76 (d, J = 8.8 Hz, 2 H), 7.22 (d, J = 8.8 Hz,
2 H), 7.27–7.27 (m, 1 H), 7.32–7.34 (m, 2 H), 7.41–7.43 (m, 2 H),
8.19 (s, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 39.8, 40.4,
112.8, 123.2, 128.1, 128.5, 128.6, 130.4, 134.1, 134.6, 140.1,
1,1Ј-(4-Phenyl-1,4-dihydropyridine-3,5-diyl)diethanone (4ep): Yellow
solid (71 mg, 59%). 1H NMR (500 MHz, CDCl3): δ = 2.17 (s, 6
H), 5.19 (s, 1 H), 6.66 (br. s, 1 H), 7.12 (t, J = 7.4 Hz, 1 H), 7.22
(dd, J = 7.9, 7.4 Hz, 2 H), 7.28 (d, J = 5.1 Hz, 2 H), 7.33 (d, J =
7.9 Hz, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 25.4, 35.6,
150.4 ppm. IR (neat): ν = 3102 (w), 2892 (br), 1677 (m), 1601 (m),
˜
1568 (w), 1521 (m), 1483 (s), 1454 (m), 1363 (w), 1329 (m), 1255
(s), 1198 (s), 1120 (s), 1068 (s), 948 (m), 926 (m), 911 (m), 894 (m),
871 (m), 818 (s), 771 (m), 738 (m), 729 (s), 695 (s), 635 (m), 573
(m), 531 (m) cm–1. HRMS (FAB): calcd. for C19H18N4O4 [M +
Na]+ 389.1226; found 389.1220.
119.1, 126.4, 128.2, 128.2, 134.2, 146.0, 195.4 ppm. IR (neat): ν =
˜
3275 (w), 3183 (w), 3082 (w), 1640 (m), 1624 (m), 1474 (m), 1377
(m), 1322 (m), 1292 (m), 1259 (w), 1191 (s), 1098 (m), 1074 (m),
1019 (w), 969 (m), 933 (m), 898 (m), 833 (w), 823 (w), 748 (m), 694
(s), 657 (m), 597 (m), 557 (m), 547 (m) cm–1. HRMS (FAB): calcd.
for C15H15NNaO2 [M + Na]+ 264.1000; found 264.1002.
3,5-Dinitro-4-phenyl-1,4-dihydropyridine (4el): Brown solid (67 mg,
1
55%). H NMR (500 MHz, [D6]DMSO): δ = 5.51 (s, 1 H), 7.22–
7.25 (m, 1 H), 7.31–7.32 (m, 4 H), 8.17 (s, 2 H), 10.5 (s, 1 H) ppm.
13C NMR (125 MHz, [D6]DMSO): δ = 39.9, 127.6, 128.3, 128.3,
[4-(4-Chlorophenyl)-1-(4-methoxyphenyl)-1,4-dihydropyridine-3,5-di-
132.2, 133.8, 141.5 ppm. IR (neat): ν = 3345 (br), 3096 (w), 2961
˜
1
yl]bis(phenylmethanone) (4eq): Yellow crystal (217 mg, 43%). H
(w), 1670 (m), 1619 (w), 1489 (s), 1470 (s), 1299 (s), 1240 (m), 1200
(m), 1166 (s), 1074 (s), 967 (w), 918 (s), 884 (m), 820 (m), 739 (m),
719 (m), 696 (s), 646 (m) cm–1. HRMS (FAB): calcd. for
C11H8N3O4 [M – H]– 246.0515; found 246.0518.
NMR (500 MHz, CDCl3): δ = 3.78 (s, 3 H), 5.65 (s, 1 H), 6.90 (d,
J = 8.8 Hz, 2 H), 7.08 (d, J = 8.8 Hz, 2 H), 7.20 (s, 2 H), 7.25 (d,
J = 8.2 Hz, 2 H), 7.38 (dd, J = 7.4, 7.4 Hz, 4 H), 7.44 (d, J =
8.2 Hz, 2 H), 7.45 (t, J = 7.4 Hz, 2 H), 7.52 (d, J = 7.4 Hz, 4
1,1Ј-[1-(4-Methoxyphenyl)-4-phenyl-1,4-dihydropyridine-3,5-diyl]di- H) ppm. 13C NMR (125 MHz, CDCl3): δ = 36.4, 55.7, 115.2, 119.7,
ethanone (4em): Yellow solid (57 mg, 33%). 1H NMR (500 MHz,
CDCl3): δ = 2.18 (s, 6 H), 3.86 (s, 3 H), 5.23 (s, 1 H), 7.01 (d, J = 144.3, 158.6, 194.3 ppm. IR (neat): ν = 3060 (w), 2923 (w), 2832
123.1, 128.3, 128.4, 128.5, 129.6, 131.2, 132.3, 136.4, 139.0, 140.0,
˜
9.1 Hz, 2 H), 7.13 (t, J = 7.4 Hz, 1 H), 7.24 (dd, J = 8.5, 7.4 Hz, 2
H), 7.27 (d, J = 9.1 Hz, 2 H), 7.36 (d, J = 8.5 Hz, 2 H), 7.45 (s, 2
H) ppm. 13C NMR (125 MHz, CDCl3): δ = 25.5, 35.6, 55.6, 115.2,
120.3, 123.5, 126.5, 128.2 (2 C), 136.6, 137.1, 145.5, 158.7,
(w), 1653 (w), 1613 (m), 1596 (m), 1576 (m), 1560 (m), 1511 (m),
1484 (m), 1442 (m), 1410 (w), 1339 (m), 1310 (m), 1291 (m), 1278
(m), 1228 (s), 1181 (m), 1144 (m), 1108 (m), 1089 (m), 1064 (m),
1038 (m), 1012 (m), 999 (m), 977 (m), 966 (m), 947 (m), 924 (m),
195.2 ppm. IR (neat): ν = 3070 (w), 3010 (w), 1662 (w), 1636 (s), 902 (m), 854 (m), 824 (m), 781 (m), 767 (m), 726 (m), 697 (s),
˜
5296
www.eurjoc.org
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 5281–5301

1,4-Dihydropyridines and Their Fluorescence Properties
650 (s), 607 (m), 588 (m), 570 (m) cm–1. HRMS (FAB): calcd. for (s), 654 (m), 637 (m), 578 (m), 560 (m), 542 (s) cm–1. HRMS (FAB):
C32H24ClNNaO3 [M + Na]+ 528.1342; found 528.1320.
calcd. for C20H17NNaO3 [M + Na]+ 342.1106; found 342.1117.
4-(4-Chlorophenyl)-1-(4-methoxyphenyl)-1,4-dihydropyridine-3,5-di-
carbaldehyde: (4fb): Orange crystal (270 mg, 25 %). 1H NMR
(500 MHz, CDCl3): δ = 3.87 (s, 3 H), 5.05 (s, 1 H), 7.03 (d, J =
9.1 Hz, 2 H), 7.21 (s, 2 H), 7.22 (d, J = 8.5 Hz, 2 H), 7.29 (d, J =
9.1 Hz, 2 H), 7.30 (d, J = 8.5 Hz, 2 H), 9.33 (s, 2 H) ppm. 13C
NMR (125 MHz, CDCl3): δ = 33.4, 55.7, 115.4, 122.6, 123.4, 128.4,
{4-(4-Chlorophenyl)-1-[4-(dimethylamino)phenyl]-1,4-dihydropyr-
idine-3,5-diyl}bis(phenylmethanone) (4er): Orange crystal (220 mg,
42%). 1H NMR (500 MHz, CDCl3): δ = 2.93 (s, 6 H), 5.66 (s, 1
H), 6.56 (d, J = 9.1 Hz, 2 H), 7.02 (d, J = 9.1 Hz, 2 H), 7.19 (s, 2
H), 7.25 (d, J = 8.5 Hz, 2 H), 7.36 (t, J = 7.4 Hz, 4 H), 7.43 (dd,
J = 6.8, 7.4 Hz, 2 H), 7.45 (d, J = 8.5 Hz, 2 H), 7.51 (d, J = 6.8 Hz,
4 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 36.2, 40.4, 112.8,
119.3, 123.0, 128.2, 128.4, 128.5, 129.6, 131.0, 132.1, 132.5, 139.1,
129.5, 132.6, 135.7, 142.7, 144.5, 159.2, 188.4 ppm. IR (neat): ν =
˜
3017 (w), 2829 (w), 1655 (s), 1592 (w), 1569 (m), 1510 (m), 1483
(m), 1465 (w), 1425 (w), 1406 (w), 1324 (m), 1283 (m), 1251 (m),
1202 (m), 1176 (m), 1145 (s), 1103 (m), 1088 (m), 1070 (m), 1029
(m), 1010 (m), 976 (w), 950 (m), 929 (m), 913 (m), 896 (m), 833
(m), 824 (m), 814 (m), 785 (m), 734 (m), 714 (m), 698 (m), 640 (w),
629 (w), 578 (m), 561 (m), 540 (s) cm–1. HRMS (FAB): calcd. for
C20H16ClNNaO3 [M + Na]+ 376.0716; found 376.0701.
140.7, 144.5, 149.6, 194.3 ppm. IR (neat): ν = 2859 (w), 2361 (w),
˜
1659 (m), 1625 (m), 1577 (m), 1557 (m), 1517 (m), 1483 (m), 1445
(m), 1409 (w), 1359 (m), 1343 (m), 1315 (m), 1278 (m), 1246 (m),
1225 (s), 1175 (m), 1147 (m), 1110 (m), 1103 (m), 1076 (m), 1065
(m), 1026 (m), 1011 (m), 1000 (m), 978 (m), 945 (m), 910 (w), 893
(m), 845 (m), 829 (w), 813 (m), 779 (m), 742 (m), 729 (m), 722 (m),
711 (m), 692 (m), 651 (m), 605 (m), 582 (m), 550 (m), 534 (m) cm–1.
HRMS (FAB): calcd. for C33H27ClN2NaO2 [M + Na]+ 541.1659;
found 541.1639.
Ethyl 3,5-Diformyl-1-(4-methoxyphenyl)-1,4-dihydropyridine-4-carb-
1
oxylate (4fc): Orange crystal (276 mg, 29%). H NMR (500 MHz,
CDCl3): δ = 1.27 (t, J = 7.4 Hz, 3 H), 3.86 (s, 3 H), 4.17 (q, J =
7.4 Hz, 2 H), 4.73 (s, 1 H), 7.00 (d, J = 8.5 Hz, 2 H), 7.26 (d, J =
8.5 Hz, 2 H), 7.26 (s, 2 H), 9.44 (s, 2 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 14.0, 35.1, 55.6, 61.5, 115.2, 117.9, 123.5, 135.4, 145.4,
[4-(4-Chlorophenyl)-1-(4-methoxyphenyl)-1,4-dihydropyridine-3,5-di-
yl]bis[(4-chlorophenyl)methanone] (4es): Yellow crystal (339 mg,
59%). 1H NMR (500 MHz, CDCl3): δ = 3.80 (s, 3 H), 5.59 (s, 1
H), 6.93 (d, J = 9.1 Hz, 2 H), 7.09 (d, J = 9.1 Hz, 2 H), 7.15 (s, 2
H), 7.26 (d, J = 8.5 Hz, 2 H), 7.36 (d, J = 8.5 Hz, 4 H), 7.40 (d, J
= 8.5 Hz, 2 H), 7.46 (d, J = 8.5 Hz, 4 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 36.4, 55.6, 115.3, 119.6, 123.1, 128.6, 128.7,
129.5, 129.8, 132.5, 136.2, 137.2, 137.5, 139.9, 144.0, 158.8,
159.1, 171.6, 188.2 ppm. IR (neat): ν = 2981 (w), 2909 (w), 2847
˜
(w), 1723 (m), 1670 (m), 1639 (m), 1612 (w), 1595 (w), 1573 (m),
1514 (m), 1467 (m), 1444 (m), 1433 (w), 1367 (w), 1339 (m), 1327
(m), 1309 (m), 1254 (m), 1213 (m), 1193 (m), 1155 (m), 1114 (m),
1025 (m), 957 (m), 942 (m), 902 (m), 881 (w), 837 (s), 790 (m), 773
(m), 749 (m), 722 (m), 700 (m), 576 (m), 546 (s) cm–1. HRMS
(FAB): calcd. for C17H17NNaO5 [M + Na]+ 338.1004; found
338.0993.
192.9 ppm. IR (neat): ν = 3066 (w), 2928 (w), 2836 (w), 1660 (w),
˜
1622 (m), 1586 (m), 1566 (m), 1510 (m), 1484 (m), 1448 (w), 1430
(w), 1398 (w), 1333 (w), 1310 (m), 1285 (m), 1227 (s), 1182 (m),
1171 (m), 1142 (m), 1101 (m), 1087 (m), 1058 (m), 1027 (m), 1012
(m), 982 (m), 952 (w), 942 (w), 907 (w), 887 (w), 846 (m), 827 (s),
788 (s), 755 (s), 720 (m), 688 (m), 673 (m), 628 (w), 601 (m), 584
(m), 558 (w), 535 (m) cm – 1 . H RM S ( FA B) : c al cd . for
C32H22Cl3NNaO3 [M + Na]+ 596.0563; found 596.0557.
1-(4-Chlorophenyl)-4-phenyl-1,4-dihydropyridine-3,5-dicarbaldehyde
1
(4fd): Orange solid (98 mg, 30%). H NMR (500 MHz, CDCl3): δ
= 5.06 (s, 1 H), 7.15–7.18 (m, 1 H), 7.25 (s, 2 H), 7.25–7.28 (m, 2
H), 7.32–7.35 (m, 4 H), 7.49–7.52 (m, 2 H), 9.34 (s, 2 H) ppm. 13C
NMR (125 MHz, CDCl3): δ = 33.9, 122.7, 123.7, 127.0, 128.1,
128.4, 130.5, 133.4, 141.0, 143.0, 143.7, 188.5 ppm. IR (neat): ν =
˜
[4-(4-Chlorophenyl)-1-(4-methoxyphenyl)-1,4-dihydropyridine-3,5-di-
yl]bis[(4-methoxyphenyl)methanone] (4et): Yellow solid (355 mg,
63%). 1H NMR (500 MHz, CDCl3): δ = 3.79 (s, 3 H), 3.82 (s, 6
H), 5.65 (s, 1 H), 6.88 (d, J = 8.5 Hz, 4 H), 6.91 (d, J = 9.1 Hz, 2
H), 7.11 (d, J = 9.1 Hz, 2 H), 7.20 (s, 2 H), 7.23 (d, J = 8.5 Hz, 2
H), 7.41 (d, J = 8.5 Hz, 2 H), 7.55 (d, J = 8.5 Hz, 4 H) ppm. 13C
NMR (125 MHz, CDCl3): δ = 37.0, 55.4, 55.6, 113.6, 115.1, 119.5,
122.9, 128.5, 129.5, 130.6, 131.4, 132.1, 136.5, 138.9, 144.4, 158.4,
3058 (w), 2817 (w), 1666 (s), 1655 (s), 1591 (m), 1570 (m), 1492
(m), 1452 (w), 1419 (w), 1384 (w), 1332 (m), 1301 (m), 1270 (w),
1250 (m), 1200 (s), 1147 (s), 1091 (m), 1076 (w), 1062 (m), 1012
(w), 976 (w), 949 (m), 902 (w), 887 (m), 877 (m), 836 (m), 758 (m),
721 (m), 697 (s), 653 (m), 632 (w), 566 (m), 536 (m), 529 (m) cm–1.
HRMS (FAB): calcd. for C19H14ClNNaO2 [M + Na]+ 346.0611;
found 346.0619.
162.2, 193.4 ppm. IR (neat): ν = 2933 (w), 2836 (w), 1655 (w), 1625
˜
1-[4-(Dimethylamino)phenyl]-4-phenyl-1,4-dihydropyridine-3,5-di-
carbaldehyde (4fe): Yellow solid (64 mg, 39 %). 1H NMR
(500 MHz, CDCl3): δ = 3.02 (s, 6 H), 5.09 (s, 1 H), 6.77 (d, J =
9.1 Hz, 2 H), 7.15 (t, J = 7.4 Hz, 1 H), 7.17 (s, 2 H), 7.21 (d, J =
9.1 Hz, 2 H), 7.26 (dd, J = 7.4, 6.8 Hz, 2 H), 7.37 (d, J = 6.8 Hz,
2 H), 9.33 (s, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 33.4,
40.5, 112.9, 122.6, 123.2, 126.8, 128.0, 128.3, 131.9, 144.4, 144.9,
(m), 1597 (m), 1572 (m), 1508 (s), 1487 (m), 1461 (m), 1441 (w),
1416 (w), 1333 (w), 1304 (m), 1277 (m), 1225 (s), 1165 (s), 1145
(m), 1108 (m), 1063 (m), 1026 (m), 974 (m), 897 (w), 834 (m), 806
(m), 791 (m), 754 (m), 705 (w), 683 (m), 634 (m), 603 (m), 533
(m) cm–1. HRMS (FAB): calcd. for C34H28ClNNaO5 [M + Na]+
588.1554; found 588.1536.
150.0, 188.6 ppm. IR (neat): ν = 3026 (w), 2811 (w), 1659 (m), 1645
˜
1-(4-Methoxyphenyl)-4-phenyl-1,4-dihydropyridine-3,5-dicarbalde-
hyde (4fa): Yellow solid (385 mg, 40 %). 1H NMR (500 MHz,
CDCl3): δ = 3.87 (s, 3 H), 5.07 (s, 1 H), 7.02 (d, J = 9.1 Hz, 2 H),
7.15 (t, J = 7.4 Hz, 1 H), 7.20 (s, 2 H), 7.25 (dd, J = 7.4, 7.4 Hz, 2
H), 7.30 (d, J = 9.1 Hz, 2 H), 7.36 (d, J = 7.4 Hz, 2 H), 9.33 (s, 2
H) ppm. 13C NMR (125 MHz, CDCl3): δ = 33.8, 55.7, 115.3, 122.9,
123.4, 126.8, 128.0, 128.3, 135.8, 144.2, 144.3, 159.0, 188.5 ppm.
(s), 1608 (w), 1577 (m), 1560 (m), 1521 (m), 1489 (m), 1447 (m),
1414 (m), 1376 (w), 1340 (m), 1314 (m), 1282 (m), 1256 (m), 1244
(m), 1201 (m), 1141 (m), 1060 (m), 1026 (m), 999 (m), 943 (m), 900
(m), 893 (m), 883 (m), 857 (w), 832 (m), 811 (m), 759 (m), 745 (m),
726 (m), 697 (s), 656 (m), 573 (m), 551 (m) cm–1. HRMS (FAB):
calcd. for C21H20N2NaO2 [M + Na]+ 355.1422; found 355.1421.
IR (neat): ν = 3003 (w), 2957 (w), 2827 (w), 2725 (w), 1651 (m),
1591 (w), 1567 (m), 1511 (m), 1454 (m), 1429 (w), 1381 (w), 1333
4-(4-Chlorophenyl)-1-[4-(dimethylamino)phenyl]-1,4-dihydropyr-
˜
idine-3,5-dicarbaldehyde (4ff): Yellow solid (350 mg, 32%). 1H
(m), 1307 (m), 1289 (m), 1253 (m), 1203 (m), 1180 (m), 1143 (s), NMR (500 MHz, CDCl3): δ = 3.02 (s, 6 H), 5.05 (s, 1 H), 6.77 (d,
1075 (m), 1031 (m), 1253 (m), 1180 (m), 971 (m), 944 (m), 932 (m), J = 9.1 Hz, 2 H), 7.18 (s, 2 H), 7.20 (d, J = 9.1 Hz, 2 H), 7.22 (d,
921 (m), 897 (m), 837 (s), 810 (m), 785 (w), 757 (s), 731 (m), 692
J = 8.5 Hz, 2 H), 7.31 (d, J = 8.5 Hz, 2 H), 9.31 (s, 2 H) ppm. 13C
Eur. J. Org. Chem. 2014, 5281–5301
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5297

S. Sueki, I. Shimizu et al.
FULL PAPER
NMR (125 MHz, CDCl3): δ = 33.4, 40.5, 112.9, 122.3, 123.2, 128.4,
134.4, 167.5 ppm. IR (neat): ν = 3325 (br), 3105 (w), 2979 (w), 1686
˜
129.5, 131.7, 132.5, 142.9, 145.1, 150.0, 188.4 ppm. IR (neat): ν =
(m), 1602 (m), 1531 (w), 1476 (m), 1447 (m), 1377 (m), 1285 (m),
˜
2808 (w), 1648 (s), 1580 (m), 1561 (m), 1518 (m), 1483 (m), 1443 1255 (m), 1180 (s), 1102 (s), 1090 (s), 1045 (s), 914 (w), 808 (w),
(m), 1409 (m), 1339 (m), 1312 (m), 1281 (m), 1254 (m), 1239 (m), 763 (m), 732 (m), 702 (m), 614 (w), 563 (m) cm–1. HRMS (FAB):
1201 (s), 1139 (s), 1105 (m), 1087 (m), 1062 (m), 1010 (m), 949 (m), calcd. for C12H17NNaO4 [M + Na]+ 262.1049; found 262.1050.
927 (m), 898 (m), 877 (m), 858 (m), 817 (s), 747 (m), 727 (m), 716
Diethyl 1-(4-Methoxybenzyl)-4-methyl-1,4-dihydropyridine-3,5-di-
(m), 697 (m), 628 (w), 570 (m), 545 (m) cm–1. HRMS (FAB): calcd.
carboxylate (6Ј): Yellow oil (27 mg, 15%). 1H NMR (500 MHz,
for C21H19ClN2NaO2 [M + Na]+ 389.1033; found 389.1050.
CDCl3): δ = 1.09 (d, J = 6.2 Hz, 3 H), 1.27 (t, J = 7.4 Hz, 6 H),
1-(4-Methoxybenzyl)-4-phenyl-1,4-dihydropyridine-3,5-dicarbalde-
3.79 (q, J = 6.2 Hz, 1 H), 3.81 (s, 3 H), 4.13–4.23 (m, 4 H), 4.42
(s, 2 H), 6.90 (d, J = 8.5 Hz, 2 H), 7.09 (s, 2 H), 7.14 (d, J = 8.5 Hz,
hyde (4fg): Orange solid (171 mg, 51 %). 1H NMR (500 MHz,
CDCl3): δ = 3.84 (s, 3 H), 4.65 (s, 2 H), 5.03 (s, 1 H), 6.91 (s, 2 H), 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 14.4, 23.7, 26.2, 55.3,
6.96–6.99 (m, 2 H), 7.11–7.14 (m, 1 H), 7.19–7.27 (m, 6 H), 9.23
(s, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 33.7, 55.4, 58.1,
114.8, 122.3, 126.6, 126.7, 127.9, 128.2, 129.0, 144.4, 145.1, 160.1,
57.6, 59.9, 109.6, 114.4, 128.36, 128.38, 138.1, 159.5, 167.3 ppm.
IR (neat): ν = 2949 (w), 2933 (w), 2903 (w), 2867 (w), 2836 (w),
˜
1698 (s), 1607 (w), 1579 (m), 1515 (m), 1449 (w), 1377 (w), 1305
(m), 1274 (m), 1248 (s), 1181 (s), 1095 (s), 1047 (m), 904 (w), 813
(w), 755 (w) cm–1. HRMS (ESI): calcd. for C20H25NNaO5 [M +
188.3 ppm. IR (neat): ν = 3030 (w), 2960 (w), 2821 (w), 2731 (w),
˜
1653 (m), 1614 (w), 1586 (w), 1565 (s), 1512 (m), 1493 (m), 1451
(m), 1407 (m), 1387 (m), 1367 (m), 1309 (w), 1297 (m), 1242 (m), Na]+ 382.1630; found 382.1619.
1218 (m), 1199 (m), 1176 (m), 1146 (s), 1079 (m), 1030 (m), 989
Procedure for the Oxidation of 1,4-DHP 4ca: A mixture of 1,4-
(m), 940 (m), 926 (m), 915 (m), 896 (m), 831 (m), 812 (m), 761 (m),
743 (w), 729 (m), 709 (m), 696 (s), 655 (m), 606 (m), 560 (m), 532
(m) cm–1. HRMS (FAB): calcd. for C21H19NNaO3 [M + Na]+
356.1263; found 356.1253.
DHP 4ca (60.0 mg, 0.20 mmol), urea hydrogen peroxide (UHP;
38.0 mg, 0.40 mmol), and iodine (10.0 mg, 0.04 mmol) in EtOAc
(1 mL) was stirred at room temperature for 9 h. The resulting mix-
ture was washed with satd. aq. Na2S2O3 (20 mL) and extracted
with EtOAc (3ϫ 15 mL). The combined organic layer was dried
with MgSO4, filtered, and the solvents evaporated. Removal of the
4-(4-Chlorophenyl)-1,4-dihydropyridine-3,5-dicarbaldehyde (4fh):
Brown crystal (84 mg, 23%). 1H NMR (500 MHz, CDCl3): δ =
5.02 (s, 1 H), 7.04 (s, 3 H), 7.21 (d, J = 8.5 Hz, 2 H), 7.27 (d, J = solvent in vacuo followed by column chromatography on silica gel
8.5 Hz, 2 H), 9.29 (s, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ (AcOEt/n-hexane) afforded pyridine 7 (53.0 mg, 89%).
= 33.5, 121.6, 128.4, 129.5, 141.2, 143.0, 148.5, 188.5 ppm. IR
Diethyl 4-Phenylpyridine-3,5-dicarboxylate (7): Yellow oil (53 mg,
89%). H NMR (500 MHz, CDCl3): δ = 0.97 (t, J = 6.8 Hz, 6 H),
4.07 (q, J = 6.8 Hz, 4 H), 7.19–7.20 (m, 2 H), 7.39–7.41 (m, 3 H),
9.08 (s, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 13.6, 61.6,
127.8 (2 C), 128.2, 128.2, 136.8, 149.2, 152.2, 166.0 ppm. IR (neat):
(neat): ν = 3308 (br), 3090 (w), 1645 (s), 1594 (m), 1485 (m), 1437
˜
1
(s), 1408 (m), 1368 (s), 1284 (w), 1263 (m), 1241 (m), 1185 (w),
1146 (s), 1089 (s), 1016 (m), 974 (m), 948 (m), 906 (s), 839 (m), 813
(m), 716 (m), 673 (s), 629 (m), 618 (m), 534 (s) cm–1. HRMS (FAB):
calcd. for C13H11ClNO2 [M + H]+ 248.0478; found 248.0478.
ν = 2987 (w), 2918 (w), 2849 (w), 1718 (s), 1579 (w), 1548 (w), 1456
˜
Diethyl 4-[(Ethoxycarbonyl)methyl]-1,4-dihydropyridine-3,5-dicarb- (w), 1446 (w), 1415 (w), 1392 (w), 1366 (w), 1314 (m), 1295 (m),
oxylate (5): Yellow oil (38 mg, 32%). 1H NMR (500 MHz, CDCl3):
1279 (m), 1226 (w), 1185 (s), 1119 (m), 1107 (m), 1079 (w), 1043
δ = 1.22 (t, J = 6.8 Hz, 3 H), 1.29 (t, J = 6.8 Hz, 6 H), 2.52 (d, J (w), 1018 (m), 920 (w), 856 (w), 797 (m), 773 (m), 754 (m), 743
= 5.1 Hz, 2 H), 4.04 (q, J = 6.8 Hz, 2 H), 4.20 (q, J = 6.8 Hz, 2 (m), 700 (w), 629 (w), 588 (w), 573 (w), 553 (m) cm–1. HRMS
H), 4.21 (q, J = 6.8 Hz, 2 H), 4.23 (t, J = 5.1 Hz, 1 H), 6.82 (br. s,
(FAB): calcd. for C17H17NNaO4 [M + Na]+ 322.1048; found
1 H), 7.29 (d, J = 5.1 Hz, 2 H) ppm. 13C NMR (125 MHz, CDCl3): 322.1050.
δ = 14.1, 14.3, 34.9, 40.6, 60.0, 60.1, 105.7, 135.7, 167.0, 172.2 ppm.
Procedure for the Wittig Reaction with 1,4-DHP 4fa: nBuLi in hex-
IR (neat): ν = 3331 (br), 3107 (w), 2980 (w), 1694 (s), 1602 (m),
˜
ane (0.60 mL, 1.60 mmol) was added dropwise to a stirred solution
of methyltriphenylphosphonium iodide (0.65 g, 1.60 mmol) in THF
(6 mL) at 0 °C. After 15 min, 1,4-DHP 4fa (0.13 g, 0.40 mmol) was
added to the prepared solution and stirred for 3 h at room tempera-
ture. The resulting mixture was quenched with water (10 mL) and
the aqueous layer was extracted with Et2O (3ϫ 15 mL), dried with
MgSO4, filtered, and the solvents evaporated. Removal of the sol-
vent in vacuo followed by column chromatography on silica gel
(AcOEt/n-hexane) afforded 3,5-dialkenylated 1,4-DHP 9a (0.12 g,
95%).
1476 (m), 1368 (m), 1284 (m), 1180 (s), 1066 (s), 1022 (m), 856 (w),
765 (m), 754 (m), 702 (w), 609 (w), 543 (w) cm–1. HRMS (FAB):
calcd. for C15H22NO6 [M + H]+ 312.1447; found 312.1453.
Diethyl 4-(2-Ethoxy-2-oxoethyl)-1-(4-methoxybenzyl)-1,4-dihydro-
1
pyridine-3,5-dicarboxylate (5Ј): Yellow oil (91 mg, 42%). H NMR
(500 MHz, CDCl3): δ = 1.16 (t, J = 6.8 Hz, 3 H), 1.26 (t, J =
7.4 Hz, 6 H), 2.48 (d, J = 5.1 Hz, 2 H), 3.80 (s, 3 H), 3.98 (q, J =
6.8 Hz, 2 H), 4.19 (q, J = 7.4 Hz, 4 H), 4.21 (t, J = 5.1 Hz, 1 H),
4.42 (s, 2 H), 6.89 (d, J = 8.8 Hz, 2 H), 7.16 (d, J = 8.8 Hz, 2 H),
7.17 (s, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 14.1, 14.3,
29.6, 40.8, 55.3, 57.6, 59.9, 60.1, 106.3, 114.4, 127.9, 128.7, 139.4,
1-(4-Methoxyphenyl)-4-phenyl-3,5-divinyl-1,4-dihydropyridine (9a):
Yellow solid (120 mg, 95%). 1H NMR (500 MHz, CDCl3): δ = 3.82
(s, 3 H), 4.76 (s, 1 H), 4.84 (dd, J = 1.1, 10.8 Hz, 2 H), 5.19 (dd, J
= 1.1, 17.0 Hz, 2 H), 6.29 (dd, J = 10.8, 17.0 Hz, 2 H), 6.60 (s, 2
H), 6.93 (d, J = 9.1 Hz, 2 H), 7.13 (t, J = 7.4 Hz, 1 H), 7.16 (d, J
= 9.1 Hz, 2 H), 7.24 (dd, J = 6.8, 7.4 Hz, 2 H), 7.35 (d, J = 6.8 Hz,
2 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 38.9, 55.6, 109.0,
114.8, 116.6, 121.3, 126.3, 127.9, 128.0, 128.1, 135.4, 137.8, 145.5,
159.6, 166.8, 171.7 ppm. IR (neat): ν = 2975 (w), 1930 (w), 2900
˜
(w), 2836 (w), 1693 (s), 1609 (w), 1579 (m), 1505 (m), 1460 (w),
1416 (w), 1371 (w), 1297 (w), 1278 (m), 1252 (m), 1223 (m), 1173
(s), 1070 (m), 1029 (m), 975 (w), 901 (w), 822 (w), 737 (w), 598 (w),
544 (w) cm–1. HRMS (ESI): calcd. for C26H29NNaO6 [M + Na]+
474.1893; found 474.1889.
Diethyl 4-Methyl-1,4-dihydropyridine-3,5-dicarboxylate (6): Yellow 156.8 ppm. IR (neat): ν = 3018 (w), 2938 (br), 2857 (br), 2171 (w),
˜
oil (16 mg, 17%). 1H NMR (500 MHz, CDCl3): δ = 1.03 (d, J =
6.8 Hz, 3 H), 1.21 (t, J = 6.8 Hz, 6 H), 3.71 (q, J = 6.8 Hz, 1 H),
2163 (w), 2036 (w), 2022 (w), 2008 (w), 1656 (m), 1610 (m), 1593
(w), 1580 (w), 1509 (s), 1489 (m), 1464 (w), 1451 (w), 1433 (w),
4.06–4.17 (m, 4 H), 6.85 (br. s, 1 H), 7.12 (d, J = 5.1 Hz, 2 H) ppm. 1339 (w), 1319 (w), 1282 (m), 1257 (m), 1243 (s), 1209 (m), 1178
13C NMR (125 MHz, CDCl3): δ = 14.3, 23.2, 26.2, 59.9, 108.7, (m), 1119 (w), 1077 (w), 1058 (m), 1027 (m), 997 (m), 951 (w), 877
5298
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© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 5281–5301

1,4-Dihydropyridines and Their Fluorescence Properties
(m), 865 (m), 830 (s), 810 (m), 777 (m), 758 (m), 703 (m), 640 (w),
624 (m), 598 (m), 532 (m) cm–1. HRMS (FAB): calcd. for
C22H21NO [M]+ 315.1623; found 315.1628.
HRMS (FAB): calcd. for C28H29NNaO5 [M + Na]+ 482.1943;
found 482.1950.
Diethyl (2E,2ЈE)-3,3Ј-{1-[4-(Dimethylamino)phenyl]-4-phenyl-1,4-di-
hydropyridine-3,5-diyl}diacrylate (9e): Orange solid (148 mg, 80%).
1H NMR (500 MHz, CDCl3): δ = 1.26 (t, J = 7.4 Hz, 6 H), 2.99
(s, 6 H), 4.08–4.20 (m, 4 H), 4.67 (s, 1 H), 5.86 (d, J = 15.3 Hz, 2
H), 6.76 (d, J = 9.1 Hz, 2 H), 6.83 (s, 2 H), 7.14 (d, J = 9.1 Hz, 2
H), 7.17 (t, J = 7.4 Hz, 1 H), 7.27 (d, J = 15.3 Hz, 2 H), 7.27 (dd,
J = 7.4, 6.8 Hz, 2 H), 7.35 (d, J = 6.8 Hz, 2 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 14.3, 39.3, 40.7, 60.0, 112.9, 113.1, 115.8,
122.3, 126.9, 127.8, 128.5, 132.9, 134.3, 143.8, 144.0, 149.2,
General Procedure for the Synthesis of 3,5-Substituted-Alkenylated
1,4-DHPs 9: A solution of Horner–Wadsworth–Emmons reagent
(6.0 equiv.) in THF (6 mL) was added dropwise to a suspension of
NaH (6.0 equiv.) in THF (6 mL) at 0 °C. After stirring for 15 min,
1,4-DHP 4f (1.0 equiv.) was added to the reaction mixture and the
solution was heated at reflux for 3–17 h. The resulting mixture was
quenched with satd. aq. NH4Cl. The aqueous layer was extracted
with CH2Cl2 (3ϫ 15 mL ), dried with MgSO4, filtered, and the
solvents evaporated. Removal of the solvent in vacuo followed by
column chromatography on silica gel (AcOEt/n-hexane) afforded
3,5-substituted-alkenylated 1,4-DHP 9.
167.6 ppm. IR (neat): ν = 2982 (w), 1696 (m), 1635 (w), 1603 (m),
˜
1550 (m), 1519 (m), 1491 (w), 1389 (w), 1363 (w), 1339 (m), 1303
(m), 1277 (m), 1239 (m), 1209 (m), 1146 (s), 1076 (m), 1065 (m),
1036 (m), 977 (m), 955 (m), 875 (w), 849 (m), 819 (m), 758 (m),
730 (w), 699 (m), 656 (m), 611 (w), 582 (w), 556 (m), 542 (m) cm–1.
HRMS (FAB): calcd. for C29H32N2NaO4 [M + Na]+ 495.2260;
found 495.2241.
(2E,2ЈE)-3,3Ј-[4-(4-Chlorophenyl)-1-(4-methoxyphenyl)-1,4-dihydro-
pyridine-3,5-diyl]bis(1-phenylprop-2-en-1-one) (9b): Red solid
(94 mg, 90%). 1H NMR (500 MHz, CDCl3): δ = 3.86 (s, 3 H), 4.95
(s, 1 H), 6.97 (d, J = 15.3 Hz, 2 H), 6.98 (s, 2 H), 6.99 (d, J =
8.5 Hz, 2 H), 7.23 (d, J = 8.5 Hz, 2 H), 7.31 (d, J = 8.5 Hz, 2 H), Diethyl 1-(4-Methoxyphenyl)-2-methyl-4-phenyl-1,4-dihydropyr-
1
7.42 (d, J = 8.5 Hz, 2 H), 7.45 (d, J = 15.3 Hz, 2 H), 7.48 (dd, J =
7.4, 7.4 Hz, 4 H), 7.55 (t, J = 7.4 Hz, 2 H), 7.86 (d, J = 7.4 Hz, 4
H) ppm. 13C NMR (125 MHz, CDCl3): δ = 39.5, 55.7, 115.2, 117.0,
118.3, 122.5, 128.2, 128.5, 128.8, 129.2, 132.3, 133.0, 135.4, 136.2,
idine-3,5-dicarboxylate (11): Brown oil (140 mg, quant.). H NMR
(500 MHz, CDCl3): δ = 1.10 (t, J = 7.4 Hz, 3 H), 1.13 (t, J =
7.4 Hz, 3 H), 2.05 (s, 3 H), 3.76 (s, 3 H), 3.95–4.07 (m, 4 H), 4.99
(s, 1 H), 6.88 (d, J = 8.8 Hz, 2 H), 7.08 (t, J = 7.4 Hz, 1 H), 7.09
(d, J = 8.8 Hz, 2 H), 7.19 (dd, J = 7.4, 7.4 Hz, 2 H), 7.25 (s, 1 H),
138.8, 142.6, 144.0, 158.5, 190.0 ppm. IR (neat): ν = 3057 (w), 1650
˜
(m), 1597 (m), 1582 (m), 1533 (s), 1508 (s), 1488 (m), 1446 (m), 7.31 (d, J = 7.4 Hz, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ =
1430 (m), 1396 (w), 1344 (m), 1299 (m), 1280 (m), 1248 (m), 1204 14.2, 14.2, 17.8, 38.9, 55.5, 59.9, 59.9, 106.4, 107.8, 114.8, 126.3,
(s), 1171 (s), 1090 (m), 1064 (m), 1034 (m), 1016 (s), 971 (m), 848 127.9, 128.0, 128.7, 135.4, 139.4, 146.1, 146.9, 159.2, 166.9,
(m), 828 (m), 773 (m), 716 (m), 693 (m), 675 (m), 617 (w), 559 (m),
540 (m) cm–1. HRMS (FAB): calcd. for C36H28ClNNaO3 [M +
Na]+ 580.1655; found 580.1681.
168.0 ppm. IR (neat): ν = 2978 (w), 1692 (s), 1655 (w), 1574 (m),
˜
1509 (s), 1453 (w), 1369 (w), 1336 (w), 1285 (w), 1227 (s), 1200 (s),
1179 (s), 1060 (s), 1028 (m), 931 (w), 902 (w), 834 (m), 805 (m),
754 (m), 725 (w), 697 (m), 648 (w), 618 (w), 580 (w), 536 (w) cm–1.
HRMS (FAB): calcd. for C25H27NO5 [M]+ 421.1889; found
421.1885.
(2E,2ЈE)-3,3Ј-{4-(4-Chlorophenyl)-1-[4-(dimethylamino)phenyl]-1,4-
dihydropyridine-3,5-diyl}bis(1-phenylprop-2-en-1-one) (9c): Red so-
1
lid (121 mg, 71%). H NMR (500 MHz, CDCl3): δ = 3.00 (s, 6 H),
4.95 (s, 1 H), 6.76 (d, J = 8.5 Hz, 2 H), 6.95 (d, J = 14.7 Hz, 2 H),
6.97 (s, 2 H), 7.16 (d, J = 8.5 Hz, 2 H), 7.31 (d, J = 8.5 Hz, 2 H),
7.42 (d, J = 8.5 Hz, 2 H), 7.47 (d, J = 14.7 Hz, 2 H), 7.47 (dd, J =
6.8, 7.4 Hz, 4 H), 7.55 (t, J = 7.4 Hz, 2 H), 7.86 (d, J = 6.8 Hz, 4
H) ppm. 13C NMR (125 MHz, CDCl3): δ = 39.5, 40.6, 113.0, 116.7,
117.9, 122.3, 128.2, 128.5, 128.8, 129.2, 132.2, 132.4, 132.9, 136.0,
Diethyl 1-(4-Methoxyphenyl)-2,6-dimethyl-4-phenyl-1,4-dihydropyr-
idine-3,5-dicarboxylate (12): Yellow solid (35 mg, 8%). 1H NMR
(500 MHz, CDCl3): δ = 1.25 (t, J = 7.4 Hz, 6 H), 2.07 (s, 6 H),
3.84 (s, 3 H), 4.14 (q, J = 7.4 Hz, 4 H), 5.14 (s, 1 H), 6.93 (d, J =
8.5 Hz, 2 H), 7.03 (d, J = 8.5 Hz, 2 H), 7.17 (t, J = 7.4 Hz, 1 H),
7.28 (dd, J = 7.4, 6.8 Hz, 2 H), 7.38 (d, J = 6.8 Hz, 2 H) ppm. 13C
NMR (125 MHz, CDCl3): δ = 14.3, 18.6, 38.8, 55.5, 59.9, 105.7,
114.4, 126.1, 127.5, 128.0, 131.1, 133.0, 147.1, 147.7, 159.3,
138.9, 142.8, 144.2, 149.5, 190.0 ppm. IR (neat): ν = 3068 (w), 2821
˜
(w), 1650 (m), 1597 (w), 1582 (m), 1518 (s), 1487 (m), 1445 (m),
1398 (w), 1342 (s), 1302 (s), 1281 (s), 1208 (s), 1167 (s), 1105 (m),
168.1 ppm. IR (neat): ν = 2981 (w), 1686 (s), 1649 (w), 1581 (m),
˜
1091 (m), 1077 (m), 1033 (m), 1017 (s), 998 (m), 976 (m), 955 (m), 1510 (m), 1478 (w), 1455 (w), 1443 (w), 1381 (w), 1365 (w), 1348
934 (m), 903 (m), 850 (m), 812 (m), 772 (m), 749 (m), 730 (m), 716 (w), 1323 (w), 1296 (w), 1281 (m), 1248 (m), 1192 (s), 1140 (w),
(m), 691 (s), 674 (m), 642 (m), 619 (m), 597 (m), 550 (m), 529 1080 (m), 1028 (m), 915 (w), 862 (w), 836 (w), 812 (w), 782 (w),
(m) cm–1. HRMS (FAB): calcd. for C37H31ClN2NaO2 [M + Na]+ 756 (w), 737 (w), 696 (m), 650 (w), 617 (w), 563 (w), 540 (w) cm–1.
593.1972; found 593.1976.
HRMS (FAB): calcd. for C26H29NO5 [M]+ 435.2046; found
435.2033.
Diethyl (2E,2ЈE)-3,3Ј-[1-(4-Methoxyphenyl)-4-phenyl-1,4-dihydro-
pyridine-3,5-diyl]diacrylate (9d): Yellow solid (67 mg, 73 %). 1H
NMR (500 MHz, CDCl3): δ = 1.26 (t, J = 7.4 Hz, 6 H), 3.85 (s, 3
H), 4.08–4.20 (m, 4 H), 4.67 (s, 1 H), 5.88 (d, J = 15.3 Hz, 2 H),
Ethyl 1-(4-Methoxybenzyl)-4-phenyl-1,4-dihydropyridine-3-carb-
oxylate (13): Yellow oil (33 mg, 57%). 1H NMR (500 MHz,
CDCl3): δ = 1.12 (t, J = 7.9 Hz, 3 H), 3.81 (s, 3 H), 3.95–4.08 (m,
6.85 (s, 2 H), 6.97 (d, J = 8.8 Hz, 2 H), 7.17 (t, J = 7.4 Hz, 1 H), 2 H), 4.36 (s, 2 H), 4.52 (d, J = 5.1 Hz, 1 H), 4.89 (dd, J = 7.9,
7.20 (d, J = 8.8 Hz, 2 H), 7.28 (d, J = 15.3 Hz, 2 H), 7.28 (dd, J =
7.4, 7.4 Hz, 2 H), 7.34 (d, J = 7.4 Hz, 2 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 14.3, 39.3, 55.6, 60.0, 113.5, 115.1, 116.2,
5.1 Hz, 1 H), 5.88 (d, J = 7.9 Hz, 1 H), 6.90 (d, J = 8.8 Hz, 2 H),
7.13–7.16 (m, 1 H), 7.19 (d, J = 8.8 Hz, 2 H), 7.24–7.26 (m, 4 H),
7.35 (d, J = 1.7 Hz, 1 H) ppm. 13C NMR (125 MHz, CDCl3): δ =
122.3, 127.0, 127.8, 128.5, 133.7, 136.6, 143.6, 143.9, 158.1, 14.3, 38.5, 55.3, 57.3, 59.4, 102.0, 108.9, 114.2, 126.1, 126.5, 127.7,
167.5 ppm. IR (neat): ν = 2982 (w), 1697 (m), 1642 (w), 1609 (m), 128.1, 128.5, 129.0, 140.2, 148.1, 159.3, 168.0 ppm. IR (neat): ν =
˜
˜
1561 (m), 1510 (m), 1469 (w), 1452 (w), 1435 (w), 1402 (w), 1365 2930 (w), 2835 (w), 1683 (s), 1611 (w), 1582 (m), 1511 (m), 1490
(w), 1344 (m), 1301 (m), 1286 (m), 1244 (m), 1215 (m), 1153 (s), (w), 1452 (w), 1411 (w), 1390 (w), 1370 (w), 1304 (m), 1246 (s),
1076 (m), 1060 (m), 1032 (s), 978 (m), 907 (m), 850 (m), 816 (m), 1206 (w), 1156 (s), 1110 (w), 1072 (m), 1021 (m), 979 (w), 912 (w),
789 (m), 768 (m), 703 (m), 659 (m), 611 (w), 581 (m), 545 (m) cm–1.
836 (m), 771 (w), 755 (w), 727 (w), 698 (m), 675 (w), 597 (w), 540
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S. Sueki, I. Shimizu et al.
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Supporting Information (see footnote on the first page of this arti-
cle): 1H and 13C NMR spectra for 1,4-dihydropiridines 4aa–az,
4ba–bf, 4ca–ch, 4da–dd, 4ea–et, 4fa–fh, 5, 5Ј, 6, 6Ј, 9a–e, its deriva-
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details of synthetic routes to compounds 11–13, and crystallo-
graphic X-ray data for 4ek, 4er, and 9c.
[6]
Acknowledgments
This work was financially supported by Ministry of Education,
Culture, Sports, Science and Technology (MEXT) (in part by the
Global COE program “Center for Practical Chemical Wisdom”)
and was also a part of the outcome of research performed under a
Waseda University grant for Special Research Projects (project
number 2010A-874).
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obtained under the reaction conditions, however, we have suc-
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[16]
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1,4-Dihydropyridines and Their Fluorescence Properties
[18] CCDC-964466 (for 4ek), -964464 (for 4er) and -964465 (for 9c)
contain the supplementary crystallographic data for this paper.
These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_
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Received: April 15, 2014
Published Online: July 17, 2014
Eur. J. Org. Chem. 2014, 5281–5301
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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