Pyridine ring formation through the photoreaction of arenecarbothioamides with diene-conjugated carbonyl compounds

Article abstract of DOI:10.1039/a906965h

Irradiation of arenecarbothioamides with hexa-2,4-dienal in benzene solution gives 2-arylpyridines in moderate yields.

Full text of DOI:10.1039/a906965h

Pyridine ring formation through the photoreaction of arenecarbothioamides
with diene-conjugated carbonyl compounds†
Kazuaki Oda,* Rikiji Nakagami, Naozumi Nishizono and Minoru Machida
Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293,
Japan. E-mail: k-oda@hoku-iryo-u.ac.jp
Received (in Cambridge, UK) 27th August 1999, Accepted 19th October 1999
Table 2 Photoreaction of arenecarbothioamides 1 with 1-arylhexa-2,4-dien-
1-one 7
Irradiation of arenecarbothioamides with hexa-2,4-dienal in
benzene solution gives 2-arylpyridines in moderate yields.
Of all the naturally occurring heterocycles, the pyridine ring is
one of the most well-known simple structures. Pyridine and
fused-pyridine moieties are present in numerous natural
products, such as the quinoline and isoquinoline alkaloids,2 and
have a vast range of potential biological activities. Therefore,
many methods for pyridine ring formation have been reported.3
In addition, in fields other than the biological one, synthetic
methods for pyridine derivatives were also required and
developed. Since di- and tri-heteroaromatic compounds4 con-
taining pyridine have received significant attention in the fields
of electrical materials,5 biologically active molecules,6 chelat-
ing agents and metal–ligand chemistry,7 the synthesis of
arylpyridine derivatives has become increasingly important.
In the course of our systematic study of the photochemistry of
the arenecarbothioamide–alkene system,8 we found that photo-
reaction of arenecarbothioamides with 2-furylacrylaldehyde in
benzene proceeds via key intermediate 4-aminobut-3-enal to
give 2,3-diarylpyrrole derivatives.9 From this pyrrole forma-
tion, utilization of a diene-conjugated carbonyl as a photo-
chemical substrate for pyridine formation was suggested. Here
we report a facile synthesis of 2-arylpyridines, 2,6-diarylpyr-
idines and benzo-fused pyridines through the photoreaction of
arenecarbothioamides with diene-conjugated carbonyl com-
pounds.
1
Ar1
4
Ar2
Yield (%)
1a
1a
1a
1a
1d
1f
Ph
Ph
Ph
Ph
2-furyl
2-thienyl
4a
4b
4c
4d
4c
4d
Ph
5aa
5b
5c
32
34
28
35
30
37
3-pyridyl
2-furyl
2-thienyl
2-furyl
2-thienyl
5db
5e
5fb
a See ref. 13. b See ref. 14.
1-arylhexa-2,4-dien-1-one 4 was carried out under similar
conditions to those described above. Similarly, the expected
2,6-diarylpyridines 5 were obtained in moderate yields (Table
2).
Next, as an extension of this reaction, photoreaction of 1a
with o-vinylbenzaldehyde 6 as the dienal equivalent was
performed under similar conditions. Irradiation of 1a with 6 for
5 h gave 4-methyl-3-phenylisoquinoline15 7 (28%) and
(3-phenyl-4-isoquinolyl)methanethiol 8 (9%), accompanied by
small amounts of 9 (Scheme 1).16 Presumably, the isoquinoline
7 was derived from thiol derivative 8. In fact, thiol 8 was easily
converted to 7 by further irradiation.
From these experiments, the reaction seems to proceed in
several steps involving initial thietane 10 formation between the
thiocarbonyl and g,d-alkenyl moiety of 2, leading to the key w-
aminodienal intermediate 12,17 which subsequently cyclizes to
the pyridine derivatives 3 as shown in Scheme 2 (pathway A).
However, no evidence is available at this time to suggest if this
step is thermal or photochemical. In the case of o-vinyl-
benzaldehyde 6 as dienal analogue, formation of isoquinoline 7
Photoreaction of arenecarbothioamide 1 with hexa-2,4-dienal
2 was carried out in benzene using a high-pressure mercury
lamp through a Pyrex filter under a nitrogen atmosphere. The
results are listed in Table 1. Irradiation of benzenecarbothio-
amide 1a with 0.5 equiv.10 of 2 for 5 h exclusively gave
2-phenylpyridine 3a (32%). Further, the photoreactions of a
series of heteroaromatic thioamides 1b–f with 2 were per-
formed. As expected, the corresponding 2-arylpyridines 3b–f
were obtained in moderate yields.
In addition, preparation of 2,6-diarylpyridines was also
examined. The photolysis of arenecarbothioamide 1 with
Table 1 Photoreaction of arenecarbothioamides 1 with hexa-2,4-dienal 2
1
Ar
Yield (%)
1a
1b
1c
1d
1e
1f
Ph
3aa
3ba
3ca
3db
3eb
3fc
32
34
28
35
30
37
3-pyridyl
4-pyridyl
2-furyl
3-furyl
2-thienyl
a See ref. 11. b See ref. 4. c See ref. 12.
† Photochemistry of the Nitrogen–Thiocarbonyl Systems. Part 34. For Part
33, see ref. 1.
Scheme 1
Chem. Commun., 1999, 2371–2372
This journal is © The Royal Society of Chemistry 1999
2371

and heteroaryl-pyridines. In addition, it was shown that certain
dienal species and their analogues are potentially useful
building blocks in photosynthesis of nitrogen-containing
heterocycles. A detailed study on further synthetic application
and the reaction pathway of this reaction is in progress.
This work was supported in part by a Grant-in-Aid for High
Technology Research Programs from the Ministry of Educa-
tion, Science, Sports and Culture of Japan.
Notes and references
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10 To avoid formation of the photodimer of 2, the molar ratio of 1a and 2
was varied. As a result, the yield of 3a increased to 32% using a ratio of
2+1.
11 C. J. Pouchert and J. R. Campbell, in The Aldrich Library of NMR
Spectra, Aldrich Chemical Company, Wisconsin, 1974, vol. 9.
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Scheme 2
16 8-Methylbicyclo[4.2.0]octa-1(6),2,4-trien-7-one 9 was derived from 6
by intramolecular photocyclization. S. V. Kessar, A. K. S. Mankotia,
J. C. Scaiano, M. Barra, J. Gebicki and K. Huben, J. Am. Chem. Soc.,
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seems to proceed via thiol 8 which arises from the initially
formed thietane 10 followed by photochemical fission of the C–
S bond of the thietane ring, and then subsequent cyclization
(pathway B).
17 J. Becher, Synthesis, 1980, 589.
In this study, the new photochemical formation of pyridine
promises to have broad applications for the synthesis of aryl-
Communication 9/06965H
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Chem. Commun., 1999, 2371–2372