Microwave heating in conjunction with UV irradiation: A tool for the oxidation of 1,4-dihydropyridines to pyridines

Article abstract of DOI:10.1071/CH08414

Microwave heating is used for the preparation of 1,4-dihydropyridines and then, in conjunction with UV irradiation, is used for the efficient oxidation of the 1,4-dihydropyridines to pyridines. The oxidation reactions are performed in a sealed vessel usin

Full text of DOI:10.1071/CH08414

RESEARCH FRONT
Full Paper
CSIRO PUBLISHING
www.publish.csiro.au/journals/ajc
Aust. J. Chem. 2009, 62, 51–57
Microwave Heating in Conjunction with UV Irradiation:
a Tool for the Oxidation of 1,4-Dihydropyridines
to Pyridines
Chad M. Kormos,A Rachel M. Hull,A and Nicholas E. LeadbeaterA,B
ADepartment of Chemistry, University of Connecticut, 55 North Eagleville Road,
Storrs, CT 06269-3060, USA.
BCorresponding author. Email: nicholas.leadbeater@uconn.edu
Microwave heating is used for the preparation of 1,4-dihydropyridines and then, in conjunction with UV irradiation, is
used for the efficient oxidation of the 1,4-dihydropyridines to pyridines. The oxidation reactions are performed in a sealed
vessel using oxygen as the oxidant and an electrodeless discharge lamp as the irradiation source.
Manuscript received: 1 October 2008.
Final version: 6 December 2008.
Introduction
In our laboratory, we have focussed attention on performing
reactions using open-vessel (standard reflux) glassware. This
offers operational advantages and opens avenues for scal-
ing up chemistry safely.[22] Using the published sealed-vessel
report as our starting point, we have developed an open-vessel
protocol.[23] Working on the 5-mmol scale using benzaldehyde
(1 equiv.), ethyl acetoacetate (5 equiv.), and 28% aqueous ammo-
nium hydroxide (10 equiv.) as reagents and water (20 mL) as
solvent, we found it was possible to obtain the desired di-
hydropyridine product in 40% yield after a total reaction time
of 20 min in an open vessel, this compared with a yield of 72%
after 15 min using a sealed tube. Our lower yield was attributed
to the fact that the reaction mixture could not be heated above the
atmospheric reflux temperature, was biphasic (the organic sub-
strates being insoluble in water), and lost ammonia over time.
By adding ethanol as a cosolvent, it was possible to improve the
yield considerably to 71%. The maximum temperature reached
during the run was 84◦C.The quantity of the dicarbonyl used can
bereducedfroma3-foldtoa1.6-foldstoichiometricexcesswith-
out a sacrifice in product yield. Using our optimized conditions,
we wanted to prepare a range of 1,4-dihydropyridines as the ini-
tial focus of our current work (Fig. 1). Ethyl acetoacetate and
5,5-dimethylcyclohexane-1,3-dione (dimedone) were chosen as
the β-dicarbonyl substrates. We screened several aldehydes and
found that aromatic and aliphatic substrates can be used. When
using paraformaldehyde as a substrate, a poor conversion to the
desired product was obtained. This is not unprecedented; other
reports have shown similar results. In an alternative approach
to prepare 4-unsubstituted dihydropyridines, Vanden Eynde and
coworkers have been able to synthesize 4-unsubstituted DHPs
The Hantzsch synthesis of 1,4-dihydropyridines (DHPs) has
attracted considerable attention due to the biological properties
of many of the dihydropyridine products.[1] They serve uses in
medicine as calcium channel modulators, vasodilators, and anti-
hypertensive agents as well as NAD(P)H models to probe the
mechanism of hydrogen transfer.[2–8] The oxidation of DHPs to
the corresponding polysubstituted pyridines has also proved an
important reaction.[9] In the present paper, we briefly expand on
a route reported by us previously for fast preparation of 1,4-
dihydropyridines and then focus attention on a methodology
for their oxidation using photogenerated singlet oxygen. Both
procedures are performed using microwave heating.
Results and Discussion
The Hantzsch DHP synthesis essentially involves condensation
of an aldehyde with a β-dicarbonyl compound and ammonia
(Scheme 1).[10] Microwave heating has found use as a tool for
performing the reaction.[11] By using microwave irradiation, it
is often possible to reduce reaction times significantly as well as
improve product yields.[12] In the first report in the area, a series
of 4-aryl derivatives were prepared in a domestic microwave with
yields ranging from 15 to 52% for a reaction time of 4 min.[13]
Other protocols based around these conditions but still using
domestic apparatus have been reported.[14–20] More recently, sci-
entific microwave apparatus has been used to prepare a series
of dihydropyridines from various aldehydes (1 equiv.), alkyl
acetoacetates (6 equiv.), and 25% aqueous ammonium hydroxide
(10 equiv.).[21] Reaction times ranged from 10 to 20 min and
yields from 53 to 95%.
O
R1
O
O
O
O
R3O
OR3
∆
ϩ
2
ϩ
NH3
R1
OR3
R2
H
R2
N
H
R2
Scheme 1. Hantzsch synthesis of 1,4-dihydropyridines.
© CSIRO 2009 10.1071/CH08414
0004-9425/09/010051

RESEARCH FRONT
52
C. M. Kormos, R. M. Hull, and N. E. Leadbeater
O
O
O
O
O
O
O
O
EtO
OEt
EtO
OEt
EtO
OEt
PhHN
NHPh
N
H
N
H
N
H
N
H
4, 49%
3, n.d.
1, 70%
2, 84%
O
O
O
O
O
O
N
H
N
H
N
H
5, 92%
7, 69%
6, 86%
Fig. 1. Hantzsch synthesis of 1,4-dihydropyridines using microwave heating. Product yields shown.
under microwave irradiation by using alkyl acetoacetates in
the presence of hexamethylenetetramine as the source of the
ammonia–formaldehyde mixture.[24]
increased efficiency by combining microwave irradiation with
the photocatalytic degradation of various substrates.[46–49] Sim-
ilarly, an efficient microwave-assisted photochemical reactor
for high-temperature water digestion has been developed,[50] as
well as a method for the degradation of bromophenol blue[51]
and for the non-catalytic remediation of aqueous solutions
in the presence of H2O2.[52] Microwave-assisted photocataly-
sis using TiO2 nanotubes has been used to degrade atrazine
in aqueous solutions.[53] Hajek and coworkers have studied
the effects of microwave heating and UV irradiation on 4-
tert-butylphenol.[54] From a synthetic chemistry perspective,
the field is relatively unexplored. Klan and coworkers have
pioneered this area, showing the use of photochemistry in
conjunction with microwave irradiation for Norrish Type II
reactions,[55] aromatic substitution of 4-nitroanisole,[56,57] and
the photo-Fries rearrangement of phenyl acetate.[58] This pre-
vious work, with one exception, was carried out in a domestic
microwave apparatus.[59–61] Nüchter and coworkers studied the
photochemical dehydrodimerisation of some hydrocarbons with
microwave heating.[62]
We wanted to use this combination of microwave and photo-
chemical technology to oxidize DHPs to pyridines using molec-
ular oxygen as the oxidant. To achieve this, we first needed to
design an apparatus that would allow us to load a vessel with
a pressure of oxygen. The vessel would also need to be of a
capacity large enough to hold an EDL. As a starting point, we
used our design for a gas-loading attachment for our monomode
microwave apparatus.[63] We developed a similar attachment that
would interface with a quartz reaction vessel in a multimode
microwave unit (Milestone MicroSynth). The vessel sits in a
protective cover that has a small window towards the bottom,
through which it is possible to see if the EDL is illuminated and
record the vessel temperature via an infrared sensor located in the
side of the microwave cavity. The internal temperature can also
be monitored using a fibre-optic probe placed inside a ceramic
thermal well. The gas is loaded through a fitting located in the
vessel screw-cap top. The vessel and its top are shown in Fig. 2a
and the apparatus in use is shown in Fig. 2b. We were thus able
to load the vessel with gas and monitor the pressure during the
course of the reaction.
A range of oxidants have been used to transform 1,4-DHPs
to the corresponding substituted pyridines with varying degrees
of success. Examples include potassium permanganate,[25]
heteropolyacids,[26] solid-supported pyridinium chlorochromate
(PCC),[27] silica-supported ferric nitrate,[28] 2,3-dichloro-5,6-
dicyano-1,4-benzoquinone (DDQ),[29] bismuth nitrate,[11] ceric
ammonium nitrate,[30] and t-butylhydroperoxide.[31] Problems
include low product yield, the use of strong oxidants, long reac-
tion times, and the need for a significant excess of the oxidant.
To overcome the issues of long reaction times and low yields,
microwave heating has been used as a tool.[32] However, these
procedures still often require large excesses of toxic oxidants as
reagents.
The cleanest oxidant that could be used for converting 1,4-
DHPs to pyridines is molecular oxygen. In the literature, there
are numerous physical organic chemistry studies into the inter-
action of molecular oxygen with 1,4-DHPs, sparked from the
desire to understand their biological properties.[33] Alongside
these reports, there have been studies into the photochemistry
of 1,4-DHPs.[34,35] Bringing these together, the clean oxidation
of DHPs involving the use of photogenerated singlet oxygen
(1O2) should be possible. However, this reaction is slow at room
temperature and atmospheric pressure.[36–39]
An area that is starting to be explored is the combination
of microwave and photochemical irradiation. Although a few
reports have appeared in the literature, the synthetic potential
of the technique has not been explored in depth. The electrode-
less discharge lamps (EDLs) used in these studies have been
around since the 1960s, when it was first discovered that a
high-frequency electromagnetic field can trigger gas discharge
leading to the emission of electromagnetic radiation.[40–42]
Using these EDLs, it is possible to place the lamp directly into a
microwave vessel and run a reaction under simultaneous UV and
microwave irradiation. As a range of filling gases can be placed
into EDLs, the emission wavelength can be varied, increasing
the scope of the methodology.[43–45] In the field of environ-
mental chemistry, there have been several reports demonstrating

RESEARCH FRONT
Oxidation of 1,4-Dihydropyridines to Pyridines
53
(a)
O
O
O
O
MW/hν
EtO
OEt
EtO
OEt
ϩ O2
N
H
N
1
8a
Scheme 2. Combination of photochemistry and microwave heating for the
oxidation of 1,4-dihydropyridines to the corresponding pyridines.
acetonitrile was a suitable compromise. It was possible to heat
this solvent while at the same time keeping the EDL illuminated
throughout the entire course of the reaction.
Using diethyl 2,6-dimethyl-4-phenyl-1,4-dihydropyridine-
3,5-dicarboxylate 1 as substrate, we started to explore conditions
for performing the oxidation reaction (Scheme 2). We loaded
the reaction vessel with the DHP and the EDL. It was not pos-
sible to stir the reaction mixture owing to the fact that the EDL
rested on the bottom of the reaction vessel. Loading the ves-
sel with 1000 kPa of oxygen and heating to 150◦C using an
initial microwave power of 400W and holding at this temper-
ature for 30 min led to the formation of a small quantity of
the desired pyridine product 8a. Unfortunately, once the reac-
tion mixture reached temperature, the microwave power dropped
substantially, causing the EDL to stop emitting light. To over-
come this problem, we made some modifications to the method.
The first was to use simultaneous cooling in conjunction with the
microwave heating.[64] By removing heat from the reaction ves-
sel, it was possible to increase the microwave energy required to
maintain the target temperature, which allowed the EDL to con-
tinue emitting light. This was achieved by inserting an air line
between the quartz vessel and the protective cover and passing
air over the vessel surface during the course of the reaction. We
then took a closer look at the microwave heating profile to deter-
mine the average microwave power input during the hold time
at 150◦C. Finding that this was 226W, we then went back and
performed the reaction in a two-stage program. In the first stage,
a microwave power of 600W was used to ramp the reaction mix-
ture to the desired temperature of 150◦C and initiate emission
from the EDL. In stage 2, we set the maximum microwave power
allowed to 250W for the 30-min duration of the hold time. By
doing this, once the reaction mixture had reached 150◦C, a fairly
constant power was applied to hold it at temperature. The result
was that the EDL remained illuminated during the entire course
of the reaction. Using this method, we obtained a quantitative
conversion of 1 to 8a (Table 1, entry 1). Shortening the reaction
time had a deleterious effect on the product yield, as did perform-
ing the reaction at a higher temperature (Table 1, entries 2 and 3).
Performing the reaction in an open vessel at reflux with the EDL
in place and simply bubbling oxygen through the solution for the
duration of the run gave only an 11% yield of the desired pyridine
product (Table 1, entry 4). Thus, our optimal conditions were:
1000 kPa O2, microwave (MW), irradiation with UV light (hν),
150◦C, 30 min.
(b)
Fig. 2. Photographs of (a) the vessel assembly used for photooxidation
chemistry, and (b) the apparatus in use.
We next turned our attention to developing conditions for the
oxidation reaction.At the outset, we knew that the key to the suc-
cess of the procedure was going to be finding a set of conditions
under which the EDL would remain illuminated throughout the
reaction. We first screened a range of potential solvents for
the reaction. Not surprisingly, those that had a high dielectric
constant heated very well but, because they absorbed much of
the microwave irradiation, did not allow the EDL to illuminate.
Low dielectric constant solvents such as hexane, although they
heated slowly and the EDL illuminated, were incompatible with
the oxidation chemistry because of poor substrate solubility.
We decided to focus on moderately microwave-absorbent sol-
vents in which the DHP substrates were soluble. We found that
With a set of conditions in hand, we needed to perform
control studies. First, we ran the reaction using 1 as substrate
without the EDL in place and obtained a 17% yield of 8a
(Table 1, entry 5). We then performed the reaction with the EDL
in the vessel but no overpressure of oxygen, instead using a
1000 kPa-nitrogen loading. In this case, we obtained a 20% con-
version to 8a (Table 1, entry 6). These experiments show that

RESEARCH FRONT
54
C. M. Kormos, R. M. Hull, and N. E. Leadbeater
Table 1. Oxidation of 1 to 8a under various reaction conditions
Reactions were run in a sealed tube, loaded with 1 (100 mg), in acetonitrile
(7.5 mL). An initial microwave irradiation power of 600W was used, the
temperature being ramped from room temperature to the desired temperature
and held until a total reaction time of 30 min had elapsed
the desired pyridine unsubstituted in the 4-position. A similar
strategy could be applied in the solid-phase synthesis of
pyridines. Starting from an immobilized secondary aldehyde,
the DHP could be built on the support and then photochemically
cleaved in a traceless manner to yield the desired pyridine.
Entry
Conditions
Conversion [%]A
1
2
3
4
5
6
1000 kPa O2, hν, 150◦C, 30 min
1000 kPa O2, hν, 150◦C, 20 min
1000 kPa O2, hν, 180◦C, 30 min
Bubbling O2, 85◦C, 30 min
1000 kPa O2, 150◦C, 30 min
1000 kPa N2, hν, 150◦C, 30 min
100
68
46
12
17
20
Summary
In summary, we have built on our previously reported method-
ology for the preparation of 1,4-DHPs using microwave heating.
We then report for the first time the use of tandem microwave
heating and UV irradiation for the efficient oxidation of DHPs
to pyridines. The oxidation reactions are performed in a sealed
vessel using oxygen as the oxidant and an EDL as the irradiation
source. We show that both oxygen and UV irradiation are key to
the success of the reaction. The one parameter in the oxidation
that we cannot probe unequivocally is the need for heating in
conjunction with irradiation.This being said, our methodology is
significantly faster than those published previously using photo-
activation in the presence of molecular oxygen. The outcome
of the oxidation depends on the DHP substrate used. When the
substituent at the 4-position of the DHP ring is an aromatic ring,
the only product observed is the substituted pyridine. When an
alkyl group is in the 4-position, we also see formation of the
corresponding pyridine product that has been de-alkylated at the
4-position. The extent to which de-alkylation occurs depends on
whether the substituent is primary or secondary. In the case of
DHPs generated from dimedone, no oxidation is observed on
photolysis under an oxygen atmosphere. Work is under way to
probe in more detail the mechanism of the reaction as well as
extend the application of tandem microwave heating and UV
irradiation to other organic transformations.
ADetermined by NMR spectroscopy, weighing the product obtained and
using liquid chromatography mass spectrometry.
both oxygen and UV irradiation are key to the success of the
reaction. Our findings are contrary to the recent report on the
photochemistry of 4-phenyl-1,4-dihydropyridines bearing a sub-
stituent on the phenyl ring that suggested that the photooxidation
does not require molecular oxygen.[65] We find that the conver-
sion of the DHP to the pyridine is very facile when performed
under our reaction conditions and does in fact require molecular
oxygen.
We screened a range of DHP substrates under our oxidation
conditions in order to probe the scope of the methodology. The
results are shown in Table 2. When the group at the 4-position of
the DHP ring is an aromatic ring, the only product observed is the
4-substituted pyridine (Table 2, entries 1 and 2). However, when
an alkyl group is in the 4-position, we also see formation of the
corresponding pyridine product that has been de-alkylated at the
4-position. The ratio of the two products depends on the nature
of the alkyl substituent. When it is a methyl group (Table 2,
entry 3), we obtain mainly the product with the methyl group
intact. Moving to a pentyl group increases the proportion of de-
alkylated product (Table 2, entry 4). When the carbon attached
to the 4-position of the DHP ring is secondary, more exten-
sive de-alkylation is observed (Table 2, entry 5). When moving
from simple DHPs to those derived from dimedone, none of
the desired oxidation product is formed (Table 2, entries 7 and
8). Instead, mainly starting material with small quantities of
uncharacterized photoproducts are obtained.
Putting our results in context, the oxidative de-alkylation
of the 4-position in substituted DHP substrates has been
observed previously using standard oxidants[66] and also
photochemically,[36,37] particularly in the case of 4-benzyl- and
sec-alkyl-substituted examples. However, there is often a mix-
ture of both the desalkyl product and that with the alkyl group
still intact. Our methodology, particularly in the case of the
cyclohexyl-substituted DHP, shows that the formation of the
unsubstituted pyridine can be effected almost quantitatively.
From a mechanistic perspective, the increased propensity toward
photochemicalcleavageofanalkylsubstituentisnotunexpected,
a secondary radical being more stable than a primary one. By
using cyclohexane carboxaldehyde or the cheaper isobutyralde-
hyde as a reagent in the preparation of DHPs, it would be possible
ultimately to generate pyridines bearing no substituent at the
4-position. This would overcome the issues associated with poor
yields when using formaldehyde as a reagent for DHP synthesis.
Although the DHP would bear a secondary alkyl group in the
4-position, on photolysis, this would be lost to yield exclusively
Experimental
Description of the Apparatus
The apparatus used for preparing the dihydropyridines has been
described previously.[23] The oxidation reactions were con-
ducted using a commercially available multimode microwave
unit (Milestone MicroSynth).The instrument was equipped with
two magnetrons with combined continuous microwave output
power from 0 to 1000W. One quartz reaction vessel (45 mL
capacity)wasemployed.Thereagentswereplacedintothequartz
tube, this in turn being placed into a protective sleeve and sealed
with a screw-top before being loading into a stand inside the
microwave cavity. The sleeve, made of a high-temperature resin
material and reinforced with fibreglass, was spring loaded at the
bottom such that when the top was screwed down, the spring was
compressed, holdingthevesselintightcontactwiththetop. Inthe
screw top there was a thermal well and a hole with a screw thread.
Direct temperature monitoring and control was achieved via a
fibre-optic probe inserted into the thermal well.The reaction ves-
sel was loaded with gas by attachment of a narrow-gauge Teflon
tube to the vessel top by means of the screw thread. The vessel
was pressurized from an oxygen cylinder to 1000 kPa linked to a
three-way connector. After loading, the gas cylinder was discon-
nected and the three-way connector turned to be in series with a
gauge to allow monitoring of pressure during the course of the
reaction. Reaction parameters (temperature, microwave power,
and desired time) were programmed into a controller unit. The
EDL used was produced by Milestone srl and comprised a high
purity quartz vacuum bulb containing mercury vapour.

RESEARCH FRONT
Oxidation of 1,4-Dihydropyridines to Pyridines
55
Table 2. Oxidation of 1,4-dihydropyridines with oxygen gas using microwave irradiation in conjunction with photolysis
Reactions were run in a sealed tube, loaded with 1,4-dihydropyridine (0.3 mmol) in acetonitrile (7.5 mL) and 1000 kPa oxygen.
An initial microwave (MW) irradiation power of 600W was used to heat to 150◦C and then a maximum power of 250W
was used to hold the reaction mixture at 150◦C for 30 min
O
R
O
O
R
O
O
O
O2
RЈO
ORЈ
RЈO
ORЈ
RЈO
ORЈ
MW/hν
RЉ
N
H
RЉ
RЉ
N
RЉ
RЉ
N
RЉ
a
b
Entry
Substrate
Products
Conversion [%]A
Ratio a:bB
O
O
EtO
OEt
1
1
100
100:0
N
8a
O
O
PhHN
NHPh
2
3
4
4
99
95
95
100:0
90:10
28:72
N
9a
O
O
O
O
O
O
N
N
N
H
10a
10b
O
O
O
O
3
EtO
OEt EtO
OEt
N
N
11a
11b
O
O
O
O
EtO
OEt
EtO
5
6
2
95
99
3:97
OEt
N
N
12a
11b
O
H
O
O
H
O
ButO
OtBu
ButO
OtBu
n.a.
N
N
H
13a
7
8
5
7
–
–
0
0
n.a.
n.a.
ADetermined by NMR spectroscopy, weighing the product obtained and using liquid chromatography mass spectrometry
(LC-MS).
BDetermined by LC-MS.

RESEARCH FRONT
56
C. M. Kormos, R. M. Hull, and N. E. Leadbeater
General Experimental Procedure for the Preparation
of 1,4-Dihydropyridines: Preparation of 1
the remaining pressure was carefully vented. The solvent was
removed under vacuum. 1H and 13C NMR in CDCl3 indicated
>95% conversion to 8a. Liquid chromatography mass spectro-
metry was used to verify the product and determine the propor-
tion of de-alkylation, if any. δH (CDCl3, 500 MHz) 0.91 (6H, t,
J 7.1), 2.62 (6H, s), 4.01 (4H, q, J 7.2), 7.24–7.38 (5H, m). δC
(CDCl3, 126 MHz) 14.3, 19.6, 39.6, 59.7, 104.2, 126.1, 127.8,
128.0, 143.9, 147.8, 167.7.
Benzaldehyde (0.51 mL, 5 mmol), ethyl acetoacetate (2.15 mL,
17 mmol), concentrated aqueous ammonium hydroxide (2.8 mL,
4.1 mmol), water (5 mL), and ethanol (5 mL) were combined in a
100-mL round-bottom long-neck flask equipped with a stir bar.
The flask was placed into the microwave cavity and a reflux con-
denser attached to the flask. The solution was heated to reflux
(84◦C) and then held at this temperature for a further 25 min.
The contents of the vessel were allowed to cool to 60◦C, and then
poured onto ice (30 g). The crude product was filtered, washed
with water, dissolved in ethyl acetate (50 mL), and washed with
water. The organic phase was dried over magnesium sulfate, fil-
tered, and concentrated under reduced pressure to afford diethyl
2,6-dimethyl-4-phenyl-1,4-dihydropyridine-3,5-dicarboxylate 1
(1.18 g, 72% yield) as a light yellow solid. δH (CDCl3, 500 MHz)
1.23–1.26 (6H, m), 2.34 (6H, s), 4.08–4.15 (4H, m), 5.01 (1H, s),
5.75 (bs), 7.14 (1H, t, J 6.7), 7.23 (2H, t, J 7.5), 7.30 (2H, d, J
8.0). δC (CDCl3, 126 MHz) 14.3, 19.6, 39.6, 59.7, 104.2, 126.1,
127.8, 128.0, 143.9, 147.8, 167.7.
NMR Data for Other Pyridines Prepared
in the Present Study
9a: δH (CDCl3, 500 MHz) 0.93–1.30 (6H, m), 1.32 (6H, t, J 7.1),
1.56–1.80 (5H, m), 2.32 (6H, s), 3.95 (1H, d, J 5.7), 4.13–4.27
(4H, m), 5.61 (1H, bs). δC (CDCl3, 126 MHz) 14.4, 19.5, 26.6,
26.7, 28.8, 38.4, 45.8, 59.6, 102.0, 144.4, 168.7.
10a: δH (CDCl3, 400 MHz) 2.06 (3H, s), 2.43 (6H, s), 2.48
(6H, s). δC (CDCl3, 100 MHz) 16.1, 21.8, 32.2, 135.9, 151.7,
175.6, 205.5.
11a: δH (CDCl3, 300 MHz) 0.86 (3H, m), 1.40 (3H, t, J 7.1),
1.10–1.40 (6H, m), 2.83 (6H, s), 3.98 (2H, t, J 6.6), 4.38 (4H, q,
J 7.1). δC (CDCl3, 75 MHz) 13.9, 14.2, 22.2, 22.4, 24.5, 27.3,
28.0, 61.5, 123.2, 141.1, 162.1, 165.8.
11b: δH (CDCl3, 500 MHz) 1.41 (6H, t, J 7.1), 2.85 (6H, s),
4.40 (4H, q, J 7.2), 8.69 (1H, s). δC (CDCl3, 126 MHz) 14.3,
24.4, 61.5, 123.4, 141.2, 162.1, 165.8.
13a: δH (CDCl3, 300 MHz) 1.57 (18H, s), 2.78 (6H, s), 8.52
(1H, s). δC (CDCl3, 75 MHz) 24.5, 28.2, 82.3, 124.9, 141.0,
161.0, 165.2.
NMR Data for Other 1,4-Dihydropyridines Prepared
in the Present Study
2: δH (CDCl3, 500 MHz) 0.93–1.30 (6H, m), 1.32 (6H, t, J 7.1),
1.56–1.80 (5H, m), 2.32 (6H, s), 3.95 (1H, d, J 5.7), 4.13–4.27
(4H, m), 5.61 (1H, bs). δC (CDCl3, 126 MHz) 14.4, 19.5, 26.6,
26.7, 28.8, 38.4, 45.8, 59.6, 102.0, 144.4, 168.7.
3: δH (CDCl3, 300 MHz) 0.86 (3H, t, J 7.0), 1.15–1.35
(14H, m), 2.30 (6H, s), 3.94 (1H, t, J 5.8), 4.04–4.29 (4H, m),
5.53 (1H, bs).
4: δH ([D6]DMSO, 400 MHz) 2.09 (6H, s), 5.10 (1H, s), 6.96
(2H, t, J 7.3), 7.08 (1H, t, J 6.8), 7.18–7.24 (8H, m), 7.54 (4H,
d, J 7.9), 8.05 (s, 1H), 9.28 (2H, s). δC ([D6]DMSO, 100 MHz)
17.3, 42.0, 105.7, 119.4, 122.6, 125.9, 127.1, 128.0, 128.4, 137.8,
139.5, 167.4.
Acknowledgements
The American Chemical Society Petroleum Research Fund is thanked for
funding (45433-AC1). Milestone srl is thanked for equipment support and
provision of electrodeless discharge lamps. Assistance with liquid chro-
matography mass spectrometry analysis fromTzipporah Kertesz is gratefully
acknowledged.
5: δH (CDCl3, 400 MHz) 1.10 (6H, s), 1.24 (6H, s), 2.29–2.49
(8H, m), 5.54 (1H, s), 7.09 (2H, d, J 7.8), 7.17 (1H, t, J 7.1),
7.26 (2H, m), 11.90 (1H, bs). δC (CDCl3, 100 MHz) 27.4, 29.7,
31.4, 32.8, 46.5, 47.1, 115.6, 125.8, 126.8, 128.2, 138.1, 190.4.
6: δH (CDCl3, 300 MHz) 0.76 (2H, q, J 10.9), 1.07 (6H, s),
1.09 (6H, s), 1.16–1.35 (3H, m), 1.58–1.75 (5H, m), 2.20–2.40
(8H, m), 2.49–2.68 (1H, m), 3.60 (1H, d, J 11.1), 11.5 (1H, bs).
7: δH (CDCl3, 300 MHz) 0.85 (6H, d, J 6.8), 1.07 (6H, s),
1.10 (6H, s), 2.24–2.38 (8H, m), 2.93–2.98 (1H, m), 3.48 (1H,
d, J 11.1), 11.5 (1H, bs).
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