Novel photoinduced aromatization of Hantzsch 1,4-dihydropyridines
Mei-Zhong Jin, Li Yang, Long-Min Wu, You-Cheng Liu and Zhong-Li Liu*
National Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, Gansu 730000, China.
E-mail: liuzl@lzu.edu.cn
Received (in Cambridge, UK) 11th September 1998, Accepted 6th October 1998
O
O
4
3
-Alkyl- and/or aryl-1,4-dihydro-2,6-dimethylpyridine-
,5-dicarboxylates (Hantzsch 1,4-dihydropyridines) are
H
R
hν
EtO
OEt
DHP• +
CCl4• –
+
CCl4
+
quantitatively oxidized to the corresponding pyridine deriv-
ET
atives by irradiation in CCl
transfer mechanism.
4
via a photoinduced electron
Me
N
Me
H
_
DHP 1
_
+
_
Cl
A plethora of reagents has been used for oxidation of
H
1
1
,4-dihydropyridine (DHP) derivatives, a class of model
compounds of NADH and drugs for treatment of cardiovascular
diseases. Generally, strong inorganic oxidants, such as nitric
O
O
R
2
3
4
5
acid, ceric ammonium nitrate or ferric or cupric nitrates, must
be used to accomplish the oxidation. Recent developments
+
DHP•
•CCl3
EtO
Me
OEt
HCCl3
+
6
7
include using nitric oxide, pyridinium chlorochromate and
clay-supported cupric nitrate accompanied by ultrasound-
promotion8 to improve the efficiency of the aromatization.
However, yields are generally moderate and/or tedious work-up
procedures are required. We report herein a very convenient,
clean and efficient approach for the oxidation of Hantzsch
N
Me
2
Scheme 2
workers.11 Therefore, a photoinduced electron transfer mecha-
nism is proposed, as outlined in Scheme 2.
The critical step in this mechanism is the extremely fast
1
,4-dihydropyridines by direct photolysis of the substrate in
CCl . To the best of our knowledge, this is the first report on
photochemical aromatization of Hantzsch 1,4-dihydropyridines
4
4
dechlorination of the radical anion of CCl . It is well known that
(
DHPs).
alkyl and aryl halides are subject to reductive dissociation upon
accepting an electron either electrochemically or photo-
4 4
DHP 1 (1 mmol) was dissolved in 25 ml of CCl or CCl –
chemically.12 The lifetime of the radical anion of CCl
was
4
MeCN (9:1 v/v) and irradiated with a 250 W high pressure
mercury lamp in a Pyrex bottle under argon atmosphere at
ambient temperature. After irradiation the solvent was removed
under reduced pressure and the corresponding pyridine deriva-
tive 2 was obtained in pure form and almost quantitative yield
13
reported to be extremely short (less than 10 ps). Therefore, C–
Cl bond breaking and electron transfer may even take place
concertedly which, in turn, effectively circumvents the back
electron transfer and makes the reaction very efficient. Maslak
and co-workers14 have termed unimolecular fragmentation of
radical ions as mesolytic cleavage and demonstrated the
tremendous facilitation of bond cleavages obtainable from the
mesolytic processes. The present reaction involves mesolytic
cleavages of both radical anions (aniomesolysis) and radical
cations (catiomesolysis), hence, it can be considered as a double
mesolytic fragmentation reaction. The aniomesolysis helps to
prevent back electron transfer, which enhances the quantum
yield of the photolysis, and the catiomesolysis facilitates the
deprotonation from DHP. These two effects make the reaction
very efficient. This strategy may be applicable to the enhance-
ment of the efficiency of other photoinduced electron transfer
reactions. In addition, since no additional oxidant is required
(
Scheme 1). One exception is 4-(2-furyl)-DHP 1g which gave
5% of 2g together with 13% of de-furyl product 2a. The results
are summarized in Table 1.
It was found that CHCl was generated during the reaction, as
8
3
evidenced by GC, and the solution became acidic after
irradiation. Hence there is no doubt that C–Cl bond cleavage
takes place during the photolysis. Similar CCl
4
- and/or HCCl
3
-
promoted photo-fragmentation reactions have recently been
reported from this laboratory9
,10
and by Whitten and co-
O
O
O
R
O
H
R
EtO
OEt
+
EtO
OEt
hν
CCl4
+ HCCl3 + HCl
4
other than the solvent CCl , and no any waste is produced, this
Me
N
H
Me
Me
N
H
Me
reaction can also be considered as a facile green chemical
reaction for the synthesis of pyridine derivatives and may be
extended to other synthetic reactions
The authors thank the National Natural Science Foundation
of China for financial support.
1
2
Scheme 1
Table 1 Aromatization of Hantzsch dihydropyridines 1 by direct photolysis
in CCl
4
Notes and references
1
2
A. Sausins and G. Duburs, Heterocycles, 1988, 27, 291.
R. A. Janis and D. J. Triggle, J. Med. Chem., 1983, 26, 775; E. Wehinger
and R. Gross, Annu. Rep. Med. Chem., 1986, 21, 85.
Conversion Yield
Substrate
R
t/h
Product (%)
(%)
3
4
5
R. H. Boecker and F. P. Guengerich, J. Med. Chem., 1986, 29, 1596.
J. R. Pfister, Synthesis, 1990, 689.
M. Balogh, I. Hermecz, Z. Meszaros and P. Laszlo, Helv. Chim. Acta.,
1
1
1
1
1
1
1
a
b
c
d
e
f
H
Me
Et
Ph
p-MeOC
p-ClC
2-furyl
1
3
3
3
3
3
3
2a
2b
2c
2d
2e
2f
2g, 2a
~ 100
~ 100
~ 100
~ 100
~ 100
~ 100
~ 100
~ 100
~ 100
~ 100
~ 100
~ 100
~ 100
85, 13
1
984, 67, 2270.
6
7
T. Itoh, K. Nagata, Y. Matsuya, M. Miyazaki and A. Ohsawa, J. Org.
Chem., 1997, 62, 3582.
J-J. V. Eynde, A. Mayence and A. Maquestiau, Tetrahedron, 1992, 48,
6
H
4
6
H
4
g
4
63.
Chem. Commun., 1998, 2451–2452
2451
Jin, Mei-Zhong
