Photoreaction of 2-halo-N-pyridinylbenzamide: Intramolecular cyclization mechanism of phenyl radical assisted with n-complexation of chlorine radical

Article abstract of DOI:10.1021/jo001470e

The photochemical behavior of 2-halo-N-pyridinylbenzamide (1-4 in Chart 1) was studied. The photoreaction of 2-chloro-N-pyridinylbenzamides 1a, 2a, 3a, and 4 afforded photocyclized products, benzo[c]naphthyridinones (6-9 and 16), in high yield, whereas the bromo analogues 1b, 2b, and 3b produced extensively photoreduced products, N-pyridinylbenzamides (1c, 10, and 11), with minor photocyclized product. Since the photocyclization reaction of 2-chloro-N-pyridinylbenzamide is retarded by the presence of oxygen and sensitized by the presence of a triplet sensitizer, acetone or acetophenone, a triplet state of the chloro analogue is involved in the reaction. Since several radical intermediates, particularly n-complexes of chlorine radical, are identified in the laser flash photolysis of 2-chloro-N-pyridinylbenzamide, an intramolecular cyclization mechanism of phenyl radical assisted with n-complexation of chlorine radical for the cyclization reaction is proposed: the triplet state (78 kcal/mol) of the chloro analogue (1a), which is populated by the excitation of 1a undergoes a homolytic cleavage of the C-Cl bond to give phenyl and chlorine radicals; while chlorine radical holds the neighbor pyridinyl ring with its n-complexation, the intramolecular arylation of the phenyl radical with the pyridinyl ring proceeds to produce a conjugated 2,3-dihydropyridinyl radical and then the conjugated radical aromatizes to afford a cyclized product, benzo[c]naphthyridinone by ejecting a hydrogen. The photoreduction product can be formed by hydrogen atom abstraction of the phenyl a radical from the environment.

Full text of DOI:10.1021/jo001470e

J . Org. Chem. 2001, 66, 2197-2206
2197
P h otor ea ction of 2-Ha lo-N-p yr id in ylben za m id e: In tr a m olecu la r
Cycliza tion Mech a n ism of P h en yl Ra d ica l Assisted w ith
n -Com p lexa tion of Ch lor in e Ra d ica l
Yong-Tae Park,* Chang-Hee J ung, Moon-Sub Kim, and Kwang-Wook Kim
Department of Chemistry, Kyungpook National University, Taegu 702-701, Korea
Nam Woong Song and Dongho Kim
National Creative Initiative Research Center for Ultrafast Optical Properties Characterization and
Spectroscopy Laboratory, Korea Research Institute of Standards and Science, Taejon 305-600, Korea
ytpark@kyungpook.ac.kr
Received October 12, 2000
The photochemical behavior of 2-halo-N-pyridinylbenzamide (1-4 in Chart 1) was studied. The
photoreaction of 2-chloro-N-pyridinylbenzamides 1a , 2a , 3a , and 4 afforded photocyclized products,
benzo[c]naphthyridinones (6-9 and 16), in high yield, whereas the bromo analogues 1b, 2b, and
3b produced extensively photoreduced products, N-pyridinylbenzamides (1c, 10, and 11), with minor
photocyclized product. Since the photocyclization reaction of 2-chloro-N-pyridinylbenzamide is
retarded by the presence of oxygen and sensitized by the presence of a triplet sensitizer, acetone
or acetophenone, a triplet state of the chloro analogue is involved in the reaction. Since several
radical intermediates, particularly n-complexes of chlorine radical, are identified in the laser flash
photolysis of 2-chloro-N-pyridinylbenzamide, an intramolecular cyclization mechanism of phenyl
radical assisted with n-complexation of chlorine radical for the cyclization reaction is proposed:
the triplet state (78 kcal/mol) of the chloro analogue (1a ), which is populated by the excitation of
1a undergoes a homolytic cleavage of the C-Cl bond to give phenyl and chlorine radicals; while
chlorine radical holds the neighbor pyridinyl ring with its n-complexation, the intramolecular
arylation of the phenyl radical with the pyridinyl ring proceeds to produce a conjugated
2,3-dihydropyridinyl radical and then the conjugated radical aromatizes to afford a cyclized product,
benzo[c]naphthyridinone by ejecting a hydrogen. The photoreduction product can be formed by
hydrogen atom abstraction of the phenyl σ radical from the environment.
In tr od u ction
cyclic molecular systems are formed from the photocy-
clization of haloarene tethered to arene by several
linkages,6 and a photohomolytic radical mechanism is
involved in the photocyclization of N-phenylalkyl-2-
halopyridinium and N-(2-halophenyl)alkylpyridinium
salts.7 In conjunction with the study of the heterocyclic
ring formation, we recently and unexpectedly observed
that photoreaction of N-(2-halophenyl)pyridinecarboxa-
mide in a basic medium produced an intramolecular
photosubstitution product, 2-pyridinylbenzoxazole in-
stead of a photocyclization product,8 whereas photoreac-
tion of 2-chloro-N-pyridinylbenzamide (1a in Chart 1) in
a weak basic or neutral medium afforded an intramo-
lecular photocyclization product, benzo[c]naphthyridi-
none. These reactions are straightforward and valuable
for the syntheses of heterocyclic compounds such as
benzoxazole and benzonaphthyridinone derivatives. Thus,
it is desirable to develop the synthetic methods of the
Kharasch and Wolf described a synthesis of biphenyl
by photoarylation of iodobenzene in benzene in 1961.1
Since then, the intramolecular photoarylation has been
widely applied to obtain cyclized molecular systems.2 The
photocyclization of aryl halide has been reviewed by
Grimshaw and de Silva,3 Kessar and Mankotia.4a The
C-X bond cleavage in the photoreaction of aryl halide
has been also scrutinized by Bunce.4b
The intramolecular photocyclization of aryl halide has
been investigated in relation to the synthetic method and
the reaction mechanism.5 We have reported that hetero-
(1) Wolf, W.; Kharasch, N. J . Org. Chem. 1961, 26, 283.
(2) (a) Kupchan, S. M.; Wormser, H. C. J . Org. Chem. 1965, 30, 3792.
(b) Thyagarajan, B. S.; Kharasch, N.; Lewis, H. B.; Wolf, W. J . Chem.
Soc., Chem. Commun. 1967, 614. (c) Cava, M. P.; Mitchell, M. J .;
Havlicek, S. C.; Lindert, A.; Spangler, R. J . J . Org. Chem. 1970, 35,
175. (d) Forzard, A.; Brasher, C. K. J . Org. Chem. 1967, 32, 2966. (e)
Portlock, D. E.; Kane, M. K.; Bristol, J . A.; Lyle, R. E. J . Org. Chem.
1973, 38, 235.
(3) Grimshaw, J . J . Chem. Soc., Chem. Rev. 1981, 10, 181.
(4) (a) Kessar, S. V.; Mankotia, S. In CRC handbook of organic
photochemistry and photobiology; Horspool, W. H., Song, P.-S., Eds.;
CRC Press: New York, 1995; p 1218. (b) Bunce, N. J . In CRC handbook
of organic photochemistry and photobiology; Horspool, W. H., Song,
P.-S., Eds.; CRC Press; New York, 1995; p 1181.
(6) (a) Park, Y.-T.; J oo, C. H.; Choi, C.-D.; Park, K. S. J . Heterocycl.
Chem. 1991, 28, 1083. (b) Park, Y.-T.; Kim, K. S.; Lee, I.-H.; Park,
Y.-C. Bull. Korean Chem. Soc. 1993, 14, 152. (c) Park, Y.-T.; Lee,
I.-H.; Kim, Y.-H. J . Heterocycl. Chem. 1994, 31, 1625. (d) Byun, Y.-S.;
J ung, C.-H.; Park, Y.-T. J . Heterocycl. Chem. 1995, 32, 1835.
(7) (a) Park, Y.-T.; Song, N. W.; Kim, Y.-H.; Hwang, C.-G.; Kim, S.
K.; Kim, D. J . Am. Chem. Soc. 1996, 118, 11399. (b) Park, Y.-T.; Song,
N. W.; Hwang, C.-G.; Kim, K.-W.; Kim, D. J . Am. Chem. Soc. 1997,
119, 10677.
(5) (a) Grimshaw, J .; de Silva, P. A. J . Chem. Soc., Chem. Commun.
1979, 193. (b) Grimshaw, J .; de Silva, P. A. J . Chem. Soc., Chem.
Commun. 1980, 302. (c) Grimshaw, J .; de Silva, P. A. Can. J . Chem.
Soc. 1980, 58, 1880.
(8) Park, Y.-T.; J ung, C.-H.; Kim, K.-W.; Kim, H. S. J . Org. Chem.
1999, 64, 8546.
10.1021/jo001470e CCC: $20.00 © 2001 American Chemical Society
Published on Web 03/07/2001

2198 J . Org. Chem., Vol. 66, No. 7, 2001
Park et al.
Ch a r t 1
was deposited on the outside of the immersion sleeve of
the lamp and should be scraped out from time to time
during reaction. Thus, a weak basic solution for the
photoreaction of other halobenzamides, in which the
pyridinium salts were liberated, was used for conven-
ience. The reaction products and their yields in the
photoreaction of a series of 2-halo-N-pyridinylbenzamide
1-4 are summarized in Scheme 1 and Table 1.
Chlorobenzamide 2a also produced two isomeric cy-
clized products 7 (21%) and 8 (33%) with minor photo-
Fries-type products 12 (9%) and 13 (6%). Chlorobenz-
amide 3a exclusively afforded a cyclized product 9 (63%)
with small amounts of photo-Fries-type products 14 (3%)
and 15 (3%).
heterocyclic compounds and to clarify their reaction
mechanisms.
2-Chloro-N-methyl-N-pyridinylbenzamide, which can-
not exist as intramolecularly and intermolecularly hy-
drogen-bonded forms, also produced a photocyclized
product, 16 (85%), effectively.
Bromobenzamide 1b produced a photoreduced product,
N-(4-pyridinyl)benzamide (1c, 37%) with minor photo-
cyclized product. Photoreaction of 2-bromobenzamides 2b
and 3b also afforded photoreduced products, N-(3-pyridi-
nyl)benzamide (10) and N-(2-pyridinyl)benzamide (11),
respectively.
In general, o-chloro-pyridinylbenzamide 1a , 2a , and 3a
underwent intramolecular photocyclization reaction with
insignificant photo-Fries type reaction, while o-bromo
analogues 1b, 2b, and 3b took part in photoreduction
reaction with minor photocyclization reaction. The pho-
tocyclization propensities of the 2-halopyridinylbenz-
amides 1-3 are similar to that of 2-chlorobenzanilide.5b
The high yield and simple performance give their pho-
tocyclization of 2-chloro analogues preparative valuable
for the synthesis of some otherwise difficultly accessible
benzo[c]naphthyridinones.
Kin etics: Qu a n tu m Yield . First of all, the ultraviolet
absorption spectral change versus irradiation time was
measured upon irradiation of 2-chloro-N-(4-pyridinyl)-
benzamide (1a ) in acetonitrile with monochromatic light
of wavelength 270 nm (Figure 1). The spectral changes
show that photocyclization of 1a is almost the sole
reaction and that the kinetic studies for the photocy-
clization are possible under several reaction conditions.
Only two other synthetic methods for the benzonaph-
thyridinones have been reported:9-11 one is an intramo-
lecular amide formation reaction of 2-(o-hydroxylamino-
phenyl)-3-alkoxylcarbonylpyridine, followed by deoxy-
genation with phosphorus trichloride.9 The other is an
oxidative photocyclization of N-(2-pyridinyl)cyclohex-1-
enecarboxamide10 and N-pyridinylbenzamide.11
There are a few studies on the intramolecular photo-
cyclization mechanism. Grimshaw and de Silva5b reported
that the photoreaction of 2-chlorobenzanilide afforded a
sole product, phenanthridone, although the triplet energy
is not high enough for the homolytic cleavage of the C-Cl
bond, while the bromo analogue produced a photoreduced
product, benzanilide, and thus suggested a type of
anchimeric assistance mechanism whereby the phenyl
ring can, through its π-cloud, complex the developing
radical center in stretching the C-Cl bond and thus lower
the transition energy for the reaction. However, the
reaction mechanism for the cyclization is not yet clear.
Here, we wish to report the photochemical synthetic
method of the benzonaphthyridinones from the photore-
action of 2-halo-N-pyridinylbenzamide (1-4 in Chart 1)
and its reaction mechanism on the basis of the results of
the preparative, kinetic, and laser flash photolysis studies
and the known reactivity of 2-chlorobenzanilide (5 in
Chart 1).
Resu lts a n d Discu ssion
The quantum yield of the photocyclization of 1a , 4, 5,
2a , and 3a under argon was measured by the UV
absorption change at λmax of the cyclized products (at 322
nm for 1a ) and are shown in Table 2. The quantum yields
range from a value of 0.52 for 4 to 0.03 for 5. The
photocyclization reactivity of 2-chloropyridinylbenzamide
(1a , Φ ) 0.13) is four times as reactive as 2-chlorobenz-
anilide (5, Φ ) 0.03). The reactivity enhancement 2-chlo-
ropyridinylbenzamide implies that the role of pyridinyl
nitrogen is important in the cyclization and is involved
somehow. We assume that phenyl-type σ and chlorine
radicals are generated by photoreaction of 1a and then
while chlorine radical is holding the pyridinyl ring by its
n-complexation13 with n-electrons on pyridinyl nitrogen
(17 in Scheme 2), the phenyl σ radical cyclizes to give
2,3-dihydrocyclohexadienyl radical (18) and eventually
benzo[c][1,6]naphthyridinone (6).
2-Halo-N-pyridinylbenzamides (1-3 in Chart 1) were
prepared by reacting 2-halobenzoyl chlorides with the
corresponding aminopyridines. To compare the structural
effect on the photocyclization, 2-chloro-N-methyl-N-(4-
pyridinyl)benzamide (4 in Chart 1) was prepared by
methylation of 1a . The preparation details of these
haloarene will be described in the Supporting Informa-
tion.
P r ep a r a tive Rea ction . When a weak basic aqueous
acetonitrile solution of 2-chloro-N-(4-pyridinyl)benzamide
(1a , 233 mg, acetonitrile 220 mL, 0.05 N aqueous Na2-
CO3 20 mL) was irradiated with a high-pressure mercury
lamp (150 W) for 4 h, a cyclized product, benzo[c][1,6]-
naphthyridin-6(5H)-one (6), was obtained in 82% yield
(Scheme 1). In pure acetonitrile, the cyclized product 6
was obtained in high yield (86%) but a pyridinium salt
(9) Go¨rlitzer, K.; Heinrici, C. Arch. Pharm.(Weinheim) 1988, 321,
477.
(10) Ninomiya, I.; Kiguchi, T.; Yamauchi, S.; Naito, T. J . Chem. Soc.,
Perkin Trans. 1 1976, 1861.
(12) (a) Huntress, E. H.; Walter, H. C. J . Am. Chem. Soc. 1948, 70,
3702. (b) Grimmel, H. W.; Guenther, A.; Morgan, J . F. J . Am. Chem.
Soc. 1946, 68, 539.
(13) We call n-complex of Cl radical for the complex between chlorine
radical and n-electrons on pyridinyl nitrogen.
(11) Itoh, K.; Kanaoka, Y. Chem. Pharm. Bull. 1974, 22, 1431.

Photoreaction of 2-Halo-N-pyridinylbenzamide
J . Org. Chem., Vol. 66, No. 7, 2001 2199
Sch em e 1
Ta ble 1. P r od u cts a n d Th eir Yield s in th e P h otor ea ction
of 2-Ha lo-N-p yr id in ylben za m id e in Ba sic Aqu eou s
Aceton itr ile Solu tion a
of a lack of electron donation by resonance of amide
nitrogen, slows down the intramolecular arylation and
in turn a photo-Fries-type reaction can compete with the
cyclization reaction.
reaction isolated yield
mp
reactant time(h) product
(%)
(°C)
lit. mp (°C)
In the presence of oxygen, the quantum yield of the
photocyclization of 1a lowered by one-third and those of
2a and 3a also lowered by about one-half (inset, Figure
1 and Table 3). These observations imply that triplet
states are involved in the photocyclization of 1a , 2a , and
3a . This conclusion was confirmed by sensitizing the
reaction of 1a with acetone or acetophenone as sensi-
tizer: irradiation of an acetonitrile solution of 1a with
acetone (or acetophenone) at monochromatic light of
wavelength 325 ( 10 nm (or 325 ( 10 nm for acetophe-
none), in which acetone (or acetophenone) only absorbed,
produced 6 efficiently (vide infra).
Stern-Volmer plot of the photocyclization of 1a with
a triplet quencher, isoprene, has been performed (Sup-
porting Information). The plot of Φo/Φ versus isoprene
concentration gave a straight line with an intercept of
unity, indicating a triplet state involved in the reaction.
The KQτ value was 194 M-1. If KQ is assumed as the
diffusion-controlled rate in water (KQ ) 6.4 × 109 M-1
s-1),16 the lifetime of the triplet state of 1a is 30 ns (lower
limit).
It is noteworthy that the photoreduction of 1b did not
occur in the presence of oxygen: the reduced product,
N-(4-pyridinyl)benzamide (1c), was not seen in the pres-
ence of oxygen in GC [the peak of the cyclized product
was disturbed by that of the starting material, lower GC/
NPD (nitrogen and phosphorus sensitive detector), not
shown]. The reduction was also sensitized by acetophe-
none in the absence of oxygen (not shown). Thus, the
reduction is also a triplet-mediated reaction.
Kin etics: Rela tive Ra te. To decide the cyclization
mechanism, the relative reaction rates of 1a were inves-
tigated in several conditions and are shown in Table 4.
In the presence of water and aqueous base, the cyclization
of 1a was retarded, but a photoreduction was accelerated
slightly (entries 1-5 in Table 4). Probably, the retarda-
tion is attributed to the lack of the availability of
n-electrons of pyridinyl group because of hydration.
The trace amount of 1c observed in the preparative
photoreaction of 1a and the formation of 1c measured in
the kinetic studies, albeit at a low rate, are meaningful,
because they indicate the other route of phenyl-type σ
radical to the reduction.
1a
2a
4.0
6.0
6
7
8
12
13
9
14
15
6
82
21
33
9
6
63
3
3
6
37
26
42
305.4b
303-30511
305.7b
299.0b
118-119
3a
1b
5.0
2.5
275.1b
275-27611
208.0-208.5
1c
10
11
2b
3b
6.5
5.0
113-114
80-81
80-8312a
82-8412b
4
3.0
16
85
174-175
a
b
CH3CN/0.05 N aq Na2CO3 ) 11/1 (v/v). Measured by digital
scanning calorimeter (DSC).
The presence of a similar complex between chlorine
radical and pyridine derivatives has been recognized by
Breslow and co-workers14 in explanation of photochemi-
cally initiated radical chlorination of 2,3-dimethylbutane
and steroid in the presence of pyridine derivatives. This
type of complexation is also used in explanation of
regioselectivity in the reaction of chlorine atom with
quinoline derivative.15
Protonation to 1a lowered the quantum yield (0.05),
probably due to a lack of the n-electrons on pyridinyl
nitrogen by the protonation. The result supports the
assumption.
The quantum yield of photocyclization of 4 is four times
as high as that of 1a . This and preparative results for 4
indicate a conformation intramolecularly hydrogen-
bonded between chlorine and hydrogen on amide nitrogen
and/or intermolecularly hydrogen-bonded between two
amide bonds is not important in the cyclization. Rather,
a free or less conjugated conformation from 2-chloro-N-
methyl-N-pyridinylbenzamide effectively produces the
cyclized product.
The photocyclization reactivity of 3a is half as reactive
as 1a , probably because of the orientation factor of the
available ortho position of substituted pyridine toward
phenyl σ radical formed from the photohomolysis of aryl-
Cl bond. The quantum yield of the photocyclization of 2a
is lower than that of 3a . Presumably, a weak n-complex-
ation of chlorine radical with 3-pyridinyl nitrogen because
In the presence of a strong base such as NaOH, the
photocyclization reactivity lowered by one-fifth while the
photoreduction accelerated (entry 5 in Table 4). In fact
(14) (a) Breslow, R.; Brandl, M.; Hunger, J .; Turro, N.; Cassidy, K.
J . Am. Chem. Soc. 1987, 109, 7204. (b) Breslow, R.; Brandl, M.; Hunger,
J .; Adams, A. D. J . Am. Chem. Soc. 1987, 109, 3799.
(15) Khanna, R. K.; Armstrong, B.; Cui, H.; Tanko, J . M. J . Am.
Chem. Soc. 1992, 114, 6003.
(16) Calvert, J . G.; Pitts, J . N. Photochemistry; J ohn Wiley and
Sons: New York, 1966; p 625.

2200 J . Org. Chem., Vol. 66, No. 7, 2001
Park et al.
F igu r e 1. Spectral change during the photoreaction of 1a in deaerated solution (Ar) and in aerated solution (O2, inset). Irradiation
time for the deaerated solution: s, 0 min; - - -, 7.5 min; - - -, 15 min; - ‚ -, 22.5 min; - ‚‚ -, 37.5 min. Irradiation time for the
aerated solution (inset): s, 0 min; - - -, 15 min; - - -, 30 min; - ‚ -, 45 min.
Ta ble 2. Qu a n tu m Yield for th e In tr a m olecu la r
P h otocycliza tion of 2-Ch lor o-N-p yr id in ylben za m id es a n d
2-Ch lor oben za n ilid e (1a , 4, a n d 5) in Aceton itr ile u n d er
Ar gon
Ta ble 3. Qu a n tu m Yield on th e In tr a m olecu la r
P h otocycliza tion of 2-Ha lo-N-p yr id in ylben za m id e (1a , 2a ,
a n d 3a ) w ith a n d w ith ou t Oxygen
quantum yield (Φ)
reactant
product
Φ
ratio (Φx/Φ1a)
reactanta
product
with Ar
with O2
ratio (ΦAr/ΦO2)
1a
6
6
16
0.13
0.05
0.52
0.03
0.04
0.07
1.0
0.4
4.0
0.2
0.3
0.5
b
1a
2a
3a
a
6
7 + 8b
9
0.13
0.03
0.07
0.04
0.02
0.03
3.2
1.5
2.3
1a protonateda
4
5
2a
3a
a
phenthridone
Measured with 2.0 × 10-4 M reactant in 0.3% basic aqueous
7 + 8b
acetonitrile solution (2.0 × 10-4 M NaOH). The molar absorp-
b
9
tivity of 7 and 8 at 340 nm are assumed to be the same (ꢀ ) 9.7 ×
103 L/mol‚cm).
In the presence of p-toluenesulfonic acid (1 equiv). The molar
absorptivity of 7and 8 at 340 nm are assumed to be the same (ꢀ )
9.7 × 103 L/mol‚cm).
Ta ble 4. Rela tive Ra te of th e F or m a tion of th e Cyclized
a n d Red u ced P r od u cts (6 a n d 1c) in th e P h otor ea ction of
2-Ch lor o-N-(4-p yr id in yl)ben za m id e (1a ) u n d er Nitr ogen
Atm osp h er e in Sever a l Con d ition s
Sch em e 2
relative rate
reduced
cyclized
entry
solvent
CH3CNa
reaction (1c)
reaction (6)
1
2
3
tc
1.0
0.8
0.7
CH3CN/H2O (9/1)
CH3CN/H2O (9/1)
0.5 mM Na2CO3
CH3CN/H2O (9/1)
1.5 mM Na2CO3
CH3CN/H2O (9/1)
2 mM NaOH
tc
0.1
4
5
0.1
0.2
0.5
0.2
6
7
CH3OH
tc
tc
0.2
0.8
CH3CN
3 mM MMAb
a
Treatment NaOH after the reaction for liberation of pyri-
dinium salt. Methyl methacrylate. c Trace, less than 0.03.
b
configuration. The excited state of the imidol,8 which is
probably a charge-transfer species and is different from
the excited state of 1a in acetonitrile, is attributed to the
lower cyclization reactivity in a strong base. In methanol
the cyclization reaction was retarded by one-fifth. The
low reactivity of 1a in methanol can be explained by
lowering the availability of n-electrons of the pyridine
ring for a species which holds the pyridine ring for the
the UV absorption spectra of 1a changed in the presence
of a strong base such as NaOH: the λmax (247.0 nm) of
1a in acetonitrile was shifted to 294 nm in 1 M NaOH
(2%, v/v) acetonitrile, indicating the presence of an imidol

Photoreaction of 2-Halo-N-pyridinylbenzamide
J . Org. Chem., Vol. 66, No. 7, 2001 2201
F igu r e 2. Transient absorption spectra: curve a (thick solid line), measured 10 µs after the laser pulse for 1a (1.7 × 10-4 M) in
acetonitrile containing tetramethylammonium chloride (5.9 × 10-4 M) under argon; curve b (thin solid line), measured 1 ms after
the laser pulse for the same solution. The c and d curves in the left inset are the temporal profile of 286 nm transient and the
same curve in the presence of N-tert-butyl-R-phenylnitrone, respectively. The e and f curves in the middle inset are the temporal
profile of 315 nm transient and the same curve in the presence of N-tert-butyl-R-phenylnitrone, respectively. The g and h curves
are the temporal profile of 355 nm transient and the same curve in the presence of potassium hexacyanoferrate(II), respectively.
cyclization (entry 6). In the presence of a radical scav-
enger MMA (methyl methacrylate), the cyclization was
retarded (entry 7), again indicating a radical reaction
involved.
not seen at the outset of the photolysis, but is seen at
the latter stage of the reaction with digital oscilloscope.
This implies that the dichloride radical anion is not
formed unless HCl is produced in the photocyclization.
Since the dichloride radical anion is detected, counter-
partner, a phenyl σ radical should be observed.
The transient intermediate observed at about 286 nm
at 1 ms delay is assignable to phenyl σ produced by the
photohomolysis of the aryl-chlorine bond of 1a , because
the absorption region is the same as a phenyl σ radical
from N-(2-chlorobenzyl)pyridinium salt,7 and the species
is not seen in the laser photolysis of 1c (not shown). The
temporal profile of the transient species at 286 nm from
1a is shown in the left inset of Figure 2. The transient
species decays in a first-order process and its lifetime is
5.9 ms. As expected, the species is suppressed by the
addition of a radical scavenger, N-tert-butyl-R-phenylni-
trone (curve d in the left inset).
The transient species observed in 300-320 nm region
exhibits a single-exponential decay with a lifetime of 1.8
ms and a significant reduction in the presence of a radical
scavenger, N-tert-butyl-R-phenylnitrone (middle inset,
Figure 2). Thus, the transient species in this region is
assignable to a conjugated 2,3-dihydropyridinyl radical.
The diffuse transient species observed from 390 to 440
nm from photolysis of 1a is assigned to n-complex of Cl
radical with n-electron pair of pyridine moiety of 1a
(Scheme 2).
La ser F la sh P h otolysis. Transient absorption spec-
tra were obtained from the laser flash photolysis of
2-chloro-N-(4-pyridinyl)benzamide (1a ) in argon-satu-
rated acetonitrile containing tetramethylammonium chlo-
ride, as shown in Figure 2. The overall transient absorp-
tion spectrum at 10 µs delay after laser flash (thick solid
line, curve a in Figure 2) exhibited a broad spectral
feature in the entire probe wavelength region with two
rather broad absorption peaks in 300-320 nm and 330-
360 nm region and one weak and diffuse peak in 390-
440 nm region. At 1 ms delay after the flash, the
absorption increase in the shorter wavelength region
became manifest as compared with that at 10 µs delay.
In addition, the absorption band in 300-320 nm lost its
intensity, and the bands in 330-360 nm and 390-440
nm region completely disappeared (thin solid line, curve
b in Figure 2).
In this broad absorption spectra, the transient absorp-
tion at about 355 nm is believed to be due to dichloride
radical anion, Cl2•-, the lifetime of which is 15 µs in
acetonitrile (curve g in right inset, Figure 2), because the
transient absorption was suppressed by addition of
potassium hexacyanoferrate(II) (curve h in right inset,
Figure 2).17 The fact that the transient absorption of
dichloride radical anion is formed when chlorine radical
is generated in the presence of chloride anion, is well-
known.18 It is noteworthy that the transient is seen in
the laser flash photolysis of 1a even in the absence of
tetramethylammonium chloride although the band is
weak. It is also noteworthy that the transient species is
The assignment was confirmed by the following com-
petition experiment. The effects of tetramethylammo-
nium chloride (TMAC) and pyridine on the transient at
400 nm from the laser flash photolysis of 1a in acetoni-
(18) (a) Scaiano, J . C.; Barra, M.; Calabrese, G.; Siuta, R. J . Chem.
Soc., Chem. Commun. 1992, 1418. (b) J ayson, G. G.; Parson, B. J .;
Swallow, A. J . J . Chem. Soc., Faraday Trans. 1 1973, 69, 1597. (c)
Grossweiner, L. I.; Matheson, M. S. J . Phys. Chem. 1957, 61, 1089.
(17) Anbar, M.; Thomas, J . K. J . Phys. Chem. 1964, 68, 3829.

2202 J . Org. Chem., Vol. 66, No. 7, 2001
Park et al.
F igu r e 3. Transient absorption spectra: curve a (thick solid line), measured 5 µs after the laser pulse (266 nm) for 1a (1.2 ×
10-4 M) in acetonitrile under argon; curve b (thin solid line), measured 5 µs after laser pulse for the same solution with TMAC
(1.2 × 10-4 M); curve c (dot line), measured 5 µs after laser pulse for the same solution with pyridine (1.2 × 10-4 M). The curve
in the right inset are the temporal profile of 400 nm transient from 1a in acetonitrile.
Sch em e 3
Figure 4). The absorption position and lifetime of the 390
nm transient are similar to 400 nm-transient from 1a .
Thus, the 400 nm transient from 1a is assigned to the
n-complex of chlorine radical.
The physical properties of the identified transients
from the photolysis of 1a and chlorine in pyridine are
summarized in Table 5. The detection of Cl2•-, a phenyl
σ, a conjugated-2,3-dihydropyridinyl radicals, and n-
complex of chlorine radical suggests a radical-mediated
mechanism in the photocyclization.
En er getics. Interestingly enough, the UV absoption
maxima of 2-chloro-N-(4-pyridinyl)benzamide (1a , λmax
247 nm, ꢀ ) 1.5 × 104 L/mol‚cm) and 2-bromo-N-(4-
pyridinyl)benzamide (1b, λmax 247 nm, ꢀ ) 1.7 × 104
L/mol‚cm) in acetonitrile are shorter than that of unsub-
stituted N-(4-pyridinyl)benzamide (1c, λmax 259 nm, ꢀ )
1.7 × 104 L/mol‚cm), suggesting that the conformation
of 1a and 1b are less conjugated. In other words,
2-halobenzamide 1a and 1b adopt conformations which
are rather nonconjugated or distorted due to the non-
bonded ortho interaction (Chart 2). The distorted con-
formers of 1a and 1b weaken the bond strength of the
aryl-X bond for the photohomolytic cleavage. Further-
more, it is assumed that the less conjugated conformer
of the ground-state results in a localized excited state of
the 2-halopyridinylbenzamide and rises the energy level.
trile was carried out and is shown in Figure 3: the thick
solid line was obtained 5 µs after laser pulse (266 nm)
for 1a (1.2 × 10-4 M) in acetonitrile under argon; the thin
solid and dot lines were obtained 5 µs after laser pulse
for the above solution in the presence of TMAC (1.2 ×
10-4 M) and pyridine (1.2 × 10-4 M), respectively. The
•-
presence of TMAC increased the formation of the Cl2
at about 350 nm with expenditure of a transient absorp-
tion at about 400 nm. Presumably, a competition reaction
of chloride anion (Cl-) from TMAC for chlorine radical
to give dichloride anion radical with pyridinyl moiety of
1a exists (Scheme 3). In the presence of pyridine both
peaks at about 350 and 400 nm decreased. Pyridine
competes for chlorine radical with lone pair electron of
pyridinyl nitrogen of 1a .
To confirm the assignment of the n-complex of chlorine
in the photoreaction of 1a , another experiment has been
carried out. When a pyridine solution of chlorine was
irradiated with pulse laser light (355 nm), two transient
absorption spectra were obtained 5 µs and 100 µs after
the laser pulse (Figure 4). The absorption at about 390
nm 5 µs after the laser pulse disappeared at 100 µs delay.
The lifetime of the 390 nm transient was 65 µs (inset of
The excitation and fluorescence spectra of 1a in aceto-
nitrile are shown in the Supporting Information. The
resulting structured absorption and emission spectra are
mirror images, indicating the excited-state structure is
not different from that of the ground state. The spectra
show that the energy of the singlet excited state of 1a is
89 kcal/mol.
The phosphorescence measurement of 1a showed that
the onset energy of the triplet state is 78 kcal/mol. The
photocyclization of 1a is readily sensitized by triplet
sensitizers such as acetone and acetophenone (Table 6).
However, the reaction with a triplet sensitizer, benzophe-

Photoreaction of 2-Halo-N-pyridinylbenzamide
J . Org. Chem., Vol. 66, No. 7, 2001 2203
F igu r e 4. Transient absorption spectra: curve a (thick solid line), measured 5 µs after laser pulse (355 nm) of chlorine in pyridine
under argon; curve b (thin solid line), measured 100 µs after laser pulse for the same solution. The c curve in the right inset are
the temporal profile of 390 nm transient.
Ta ble 5. P h ysica l P r op er ties of th e Tr a n sien t In ter m ed ia tes fr om th e P h otolysis of 1a
none, occurred ineffectively. The sensitization reactivity
is understandable by comparing the triplet energy19 of
the sensitizer with that of 1a : the triplet energy of
benzophenone (69 kcal/mol) is lower than that of 1a (78
kcal/mol). The triplet energy of acetone (78 kcal/mol) is
high enough to induce a triplet state of 1a to undergo
the cyclization effectively, but that of acetophenone (74
kcal/mol) is a little lower than or comparable to that of
1a at room temperature. It is noteworthy that the
sensitizing cyclization of 1a with acetophenone at 10 °C
was three times efficient as compared with that at 0 °C.
This shows that the population of the appropriate triplet
state for the homolysis is increased at higher tempera-
ture.
The only problem in this interpretation is that the bond
energy of aryl-chlorine should be lower than the triplet

2204 J . Org. Chem., Vol. 66, No. 7, 2001
Park et al.
Ch a r t 2
Sch em e 4
Ta ble 6. Rela tive Ra te on th e Sen sitized
P h otocycliza tion of 1a a t 20 °Ca
19
sensitizer
acetone
acetophenone
benzophenone
no sensitizer
ET (kcal/mol)
relative rate
78
74
69
10
1.0
0.3
0.1
a
Irradiation wavelingth, 325 ( 10 nm.
energy of 1a (78 kcal/mol) or at least comparable to it.
According to previous reports,20,21 the bond energy of
aryl-chlorine is quite lowered in o-substituted chlo-
robenzene: that of o-dichlorobenzene is 86 kcal/mol. The
aryl-chlorine bond energy is 81 kcal/mol in 2-chloroben-
zoic acid. Assuming that the bond energy of aryl-chlorine
of 1a is about 81 kcal/mol, the homolytic cleavage of aryl-
chlorine bond is possible from the triplet state of 1a (78
kcal/mol) at room temperature.
Mech a n ism . The following photocyclization mecha-
nism is proposed on the basis of the above preparative,
kinetic, and laser flash photolysis studies (Scheme 4).
Upon irradiation, the distored and less conjugated con-
former of o-substituted pyridinylbenzamide is excited to
populate the singlet state and the ensuing intersystem
crossing populates the triplet state. The triplet states can
also be populated by the energy transfer of a sensitizer
such as acetone or acetophenone. The majority of the
triplet energy is assumed to reside at the 2-chlorobenzoyl
moiety, not the aminopyridinyl moiety because of the
nonconjugated system. The triplet state of the 2-chlo-
robenzoyl moiety of 1a undergoes homolytic cleavage of
the phenyl-chlorine bond to yield a phenyl σ radical and
chlorine radical, while the triplet state of the more
conjugated conformer of 1a does not experience homolytic
cleavage of the phenyl-chloride bond due to the lower
triplet energy of the conjugated conformer. The chlorine
radical interacts with the lone pair electrons on pyridinyl
nitrogen to give n-complex of chlorine radical, or/and
reacts with chloride anion to yield dichloride radical
anion, if chloride anion is formed. The photogenerated
phenyl σ radical now partitions between reacting with
the neighbor pyridine ring to form conjugated 2,3-
dihydropyridinyl radical while chlorine radical holds the
pyridinyl ring by the n-complexation of chlorine radical
(17) and the ensuing dehydrogenation of the conjugated
radical eventually proceeds to give benzo[c]naphthyridi-
none product (6), and reacting with hydrogen donor to
form the reduced product (1c). Observation of a small
amount of a photoreduced product from 1a , 2a , or 3a in
preparative scale with GC/MS22 and in the relative rate
study of 1a is in line with the radical-mediated mecha-
nism.
For 2-bromo-N-pyridinylbenzamide (1b, 2b, 3b), pho-
toreduction reactions occur because bromine radical,
which is produced from the photohomolytic cleavage of
phenyl-bromine bond, cannot hold the pyridinyl ring due
to the lack of the n-complexation of bromine radical. A
similar behavior of bromine radical was observed in
regioselectivity of quinoline derivatives.15 The triplet
energy of the more conjugated conformer which is lower
than that of the distorted and less conjugated one can
split only the aryl-bromine bond (not the aryl-chlorine
bond) to give a phenyl-type σ and bromine radicals. The
phenyl-type σ radical is mainly reduced by hydrogen
abstraction from the environment with the minor cyclized
product.
The photocyclization mechanism in which n-complex
is involved can be applied in ring formation. For example,
photoreaction of 2-chloroarene tethered to arene contain-
ing nitrogen can afford cyclized products.
The photocyclization mechanism suggests that in the
photocyclization of 2-chlorobenzanilide a π-complex of the
photogenerated chlorine radical with the phenyl ring is
involved. Further application of these mechanisms, in
which n- and π-complexes of chlorine radical are involved,
(19) Murov, S. L.; Carmichael, I.; Hug, G. L. Handbook of Photo-
chemistry, 2nd ed.; Marcel Dekker: New York, 1993; p 4.
(20) Cioslowski, J .; Liu, G.; Moncrieff, D. J . Phys. Chem. A. 1997,
101, 957.
(22) In the preparative scale, the reduced products were not
separated, although the products were identified and quantitatively
measured by GC/MS (less than 3%).
(21) Sabbah, R.; Agulia, A. R. Can. J . Chem. 1995, 73, 1538.

Photoreaction of 2-Halo-N-pyridinylbenzamide
J . Org. Chem., Vol. 66, No. 7, 2001 2205
CN/CH2Cl2/EtOH ) 6/18/1 (2.2 × 24 cm, 70-230 mesh silica
gel). The band of Rf 0.24 was identified as benzo[c][1,7]-
naphthyridin-6(5H)-one (7, 41 mg, 21%): mp (DSC) 305.7 °C;
UV (λmax in acetonitrile), 336 nm (ꢀ ) 5.5 × 103 L/mol‚cm); IR
(gas phase) 3429, 3080, 1712 cm-1; 1H NMR (200 MHz, DMSO-
d6) δ 11.90 (br. s, 1H), 8.67 (s, 1H), 8.60 (d, J ) 8.2 Hz, 1H),
8.42-8.29 (m, 3H), 7.93 (dt, J ) 1.5, 7.6 Hz, 1H), 7.78 (t, J )
7.5 Hz, 1H); MS (EI) m/z (rel intensity) 196 (100, M+). Anal.
Calcd for C12H8ON2: C, 73.46; H, 4.11; N, 14.28. Found: C,
73.43; H, 3.25; N, 14.09. The band of Rf ) 0.57 was identified
as benzo[c][1,5]naphthyridin-6(5H)-one (8, 65 mg, 34%): mp
(DSC) 299 °C; UV (λmax in acetonitrile), 340 nm (ꢀ ) 1.4 × 104
L/mol‚cm); IR (gas phase) 3428, 3083, 1711 cm-1; 1H NMR (200
MHz, DMSO-d6) δ 11.77 (br. s, 1H), 8.75 (dd, J ) 8.2, 0.6 Hz,
1H), 8.53 (dd, J ) 4.5, 1.3 Hz, 1H), 8.30 (dd, J ) 8.2, 1.3 Hz,
1H), 7.92 (dt, J ) 1.4, 7.6 Hz, 1H), 7.79-7.69 (m, 2H), 7.52
(dd, J ) 8.2, 4.5 Hz, 1H); MS (EI) m/z (rel intensity) 196 (100,
M+), 168 (27). Anal. Calcd for C12H8ON2: C, 73.46; H, 4.11;
N, 14.28. Found: C, 73.54; H, 3.44; N, 14.01. The diethyl ether
portion was also separated by HPLC (low-pressure liquid
chromatography, silica gel 230-400 mesh, φ 2.2 cm × 24 cm)
with the following order of eluents, CH2Cl2 200 mL, CH2Cl2/
CH3CN ) 50 mL/350 mL, CH3CN/CH2Cl2 ) 100 mL/250 mL,
and CH3CN 300 mL. The analysis gave photo-Fries type
products, 3-amino-2-(2-chlorobenzoyl)pyridine (12, 21.8 mg,
9%) and 3-amino-6-(2-chlorobenzoyl)pyridine (13, 15 mg, 6%,
syrup). 3-Amino-2-(2-chlorobenzoyl)pyridine (12) was identified
by the following spectral data and elemental analysis: mp
to other molecular systems and 2-chlorobenzanilides will
be described in due course.
Exp er im en ta l Section
Ma ter ia l a n d Gen er a l P r oced u r es. 2-Chlorobenzoyl chlo-
ride, 2-bromobenzoyl chloride, 4-aminopyridine, 3-aminopyri-
dine, and 2-aminopyridine (all Aldrich) were used without
further purification. Triethylamine (Aldrich) and methyl meth-
acrylate (Aldrich) were distilled prior to use. Acetonitrile and
methanol were distilled prior to use. Sodium carbonate and
sodium hydroxide (reagent grade) were used without purifica-
tion. Acetophenone (Fluka) and benzophenone (Fisher) were
used as received. Triply distilled water was used.
Melting points were measured on capillary melting point
apparatus, Thomas-Hoover or digital scanning calorimeter
(DSC). Uv/vis absorption spectra were recorded on Varian Cary
3E Spectrophotometer or Hewlett-Packard 8452A diode array
spectrophotometer. Perkin-Elmer LS-50 luminescence spec-
trophotometer with a gated photomultiplier tube detector at
77K with modification of cell compartment was used for the
phosphorescence spectra. For the fluorescence spectra, Spec-
trofluorimeter (Spex, Model FL 111) was used. Infrared spectra
were recorded on Nicolet Magna 550 FT-IR (Mattson Galax
Series 7020) spectrophotometer or Hewlett-Packard IRD
equipped 5890 Series II gas chromatograph. Gas chromato-
graph with NPD (6890 Series Hewlett-Packard) was used.
NMR spectra were recorded on Brucker Ac 200 (200 MHz)
operating at 200 MHz for proton. The 1H NMR spectra were
referenced with respect to TMS. The mass spectra were
obtained from Hewlett-Packard 5989A mass spectometer with
Hewlett-Packard 5890 series II gas chromatograph. Elemental
analysis was performed on elemental analyzer, Carlo Erba
CHNS-O E. A. 1180.
P r epar ative P h otor eaction . P h otor eaction of 2-Ch lor o-
N-(4-p yr id in yl)ben za m id e (1a ): Gen er a l P r oced u r e. To
a large (300 mL) quartz immersion well photolysis unit with
provision for circulation nitrogen was added 220 mL of an
approximately 4.2 × 10-3 M acetonitrile solution of 2-chloro-
N-(4-pyridinyl)benzamide (1a , 2a , 3a , 1b, 2b, or 3b) containing
20 mL of 0.05 N Na2CO3 aqueous solution. With nitrogen
circulation, the solution was irradiated with a 150 W mercury
lamp (high pressure) at 100 V for 4 h (The proceeding of the
reaction was followed by TLC or GC). After stripping off
solvent under reduced pressure, recrystallization (EtOH/H2O
) 8.5/1.5) gave benzo[c][1,6]naphthyridin-6(5H)-one (6, 82%):
mp (DSC) 305.7 °C (lit.11 mp 303-304.5 °C); UV (λmax in
acetonitrile) 322 nm (ꢀ ) 6.6 × 103 L/mol‚cm); IR (gas phase)
3430, 3079, 1715 cm-1; 1H NMR (200 MHz, DMSO-d6) δ 11.92
(br s, 1H), 9.55 (s, 1H), 8.62 (d, J ) 7.9 Hz, 1H), 8.48 (d, J )
5.6 Hz, 1H), 8.31 (dd, J ) 7.9, 1.1 Hz, 1H), 7.87 (dt, J ) 1.4,
7.6 Hz, 1H), 7.67 (dt, J ) 1.0, 7.6 Hz, 1H), 7.25 (dd, J ) 5.6,
0.5 Hz, 1H); MS (EI) m/z (rel intensity) 196 (100, M+), 168
(22). Anal. Calcd for C12H8ON2: C, 73.46; H, 4.11; N, 14.28.
Found: C, 73.42; H, 3.91; N, 14.30.
P h otor ea ction of 2-Br om o-N-(4-p yr id in yl)ben za m id e
(1b). The photoreaction of 1b was carried out for 2.5 h as in
the case of 1a . The photolysate of 1b was evaporated under
reduced pressure. The dissolved portion of the photolysate in
acetonitrile was separated in a column chromatograph with a
solvent mixture [CH3CN/CH2Cl2/EtOH ) 6/18/1, (v/v)]. The
band of Rf 0.39 on TLC was identified as benzo[c][1,6]-
naphthyridin-6(5H)-one (6%). The band of Rf 0.45 was identi-
fied N-(4-pyridinyl)benzamide (1c, 37%; mp, 208.0-208.5 °C).
P h otor ea ction of 2-Ch lor o-N-(3-p yr id in yl)ben za m id e
(2a ). The photoreaction of 2a (233 mg, 1 mmol) was carried
out for 6 h as in the case of 1a . After the solvent was stripped
off, the photolysate was dissolved three times in diethyl ether
(5 mL × 3) and the solid was separated from the mixture by
a centrifuge. After the solids were dissolved with methanolic
triethylamine (triethylamine (0.2 mL) and methanol (3 mL))
the solution again was evaporated to 1 mL. Analytical TLC
showed two bands of Rf 0.24 and 0.57. The bands were
separated by column chromatograph with an eluent of CH3-
1
118-119 °C; IR (gas phase) 3511, 3370, 3064, 1669 cm-1; H
NMR (200 MHz, CDCl3) δ 7.98 (dd, J ) 4.1, 1.4 Hz 1H), 7.43-
7.31 (m, 4H), 7.19 (dd, J ) 8.5, 4.1 Hz, 1H), 7.07 (dd, J ) 8.5,
1.4 Hz, 1H), 6.27 (br s, 2H); MS (EI) m/z (rel intensity) 232 (2,
M+), 198 (13), 197 (100). Anal. Calcd for C12H9ON2: C, 61.95;
H, 3.90; N, 12.04. Found: C, 61.93; H, 3.94; N, 11.71. 3-Amino-
6-(2-chlorobenzoyl)pyridine (13) was identified by the following
spectral data and elemental analysis: IR (gas phase) 3503,
1
3419, 3071, 1692 cm-1; H NMR (200 MHz, CDCl3) δ 8.04 (d,
J ) 2.8 Hz 1H), 8.00 (d, J ) 8.5 Hz, 1H), 7.44-7.34 (m, 4H),
7.01 (dd, J ) 8.5, 2.8 Hz, 1H), 4.32 (br s, 2H); MS (EI) m/z (rel
intensity) 232 (1, M+), 198 (13), 197 (100). Anal. Calcd for
C
12H9ON2: C, 61.95; H, 3.90; N, 12.04. Found: C, 61.90; H,
3.95; N, 11.97.
P h otor ea ction of 2-Br om o-N-(3-p yr id in yl)ben za m id e
(2b). The photoreaction of 2b (556 mg, 2 mmol) was carried
out for 6.5 h as described above for that of 1a . GC/MS analysis
showed that there were three products, namely photoreduced
product (major), photocyclized product, and photo-Fries-type
product. Only, the photoreduced product (103.8 mg, 26%) was
separated on column chromatography with eluent of CH3CN/
CHCl3 (φ 2.2 cm × 25 cm, 70-230 mesh silica gel): mp 113-
114 °C; UV (λmax in acetonitrile) 259 nm; IR (gas phase) 3460,
3073, 1710 cm-1;1H NMR (200 MHz, acetone-d6) δ 9.71 (br. s,
1H), 8.97 (d, J ) 2.0 Hz 1H), 8.34-8.28 (m, 2H), 8.05-7.99
(m, 2H), 7.63-7.47 (m, 3H), 7.35 (dd, J ) 8.0, 4.8 Hz, 1H); MS
(EI) m/z (rel intensity) 198 (24, M+), 105 (100). Anal. Calcd
for C12H10ON2: C, 72.71; H, 5.08; N, 14.13. Found: C, 72.45;
H, 4.96; N, 14.27.
P h otor ea ction of 2-Ch lor o-N-(2-p yr id in yl)ben za m id e
(3a ). The photoreaction of 3a (233 mg, 1 mmol) was carried
out for 5 h as described above for that of 1a . After evaporation
of solvent, recrystallization (EtOH/H2O ) 2/1) gave a photo-
cyclized product, benzo[c][1,8]naphthyridin-6(5H)-one (9, 123
mg, 63%): mp (DSC) 275.1 °C (lit.11 mp 275-276 °C); UV (λmax
in acetonitrile) 334 nm (ꢀ ) 1.2 × 104 L/mol‚cm); IR (gas phase)
3426, 3078, 1712 cm-1; 1H NMR (200 MHz, DMSO-d6) δ 11.97
(br s, 1H), 8.79 (d, J ) 8.0 Hz, 1H), 8.54-8.47 (m, 2H), 8.32
(d, J ) 7.8 Hz, 1H), 7.88 (t, J ) 7.6 Hz, 1H), 7.68 (t, J ) 7.54
Hz, 1H), 7.32 (dd, J ) 8.0, 4.7 Hz, 1H); MS (EI) m/z (rel
intensity) 196 (100, M+). Anal. Calcd for C12H8ON2: C, 73.46;
H, 4.11; N, 14.28. Found: C, 73.14; H, 3.86; N, 14.18. The
filtrate was concentrated and then separated on column
chromatography (φ 2.2 cm × 25 cm, 70-230 mesh silica gel)
with eluent of CH3CN/CH2Cl2 (1/2). Two bands (Rf 0.60, 75
mg and Rf 0.80, 7.5 mg) were obtained and identified as
2-amino-3-(2-chlorobenzoyl)pyridine (14) and 2-amino-5-(2-

2206 J . Org. Chem., Vol. 66, No. 7, 2001
Park et al.
chlorobenzoyl)pyridine (15), respectively by the following data.
2-Amino-3-(2-chlorobenzoyl)pyridine (14): mp 156-157 °C; IR
(gas phase) 3521, 3377, 3077, 1661 cm-1; 1H NMR (200 MHz,
CDCl3) δ 8.26 (dd, J ) 4.7, 1.8 Hz, 1H), 7.50-7.28 (m, 5H),
7.06 (br. s, 2H), 6.56 (dd, J ) 7.9, 4.7 Hz, 1H); MS (EI) m/z
(rel intensity) 234 (6, M+ + 2), 232 (19, M+), 198 (14), 197 (100).
Anal. Calcd for C12H8ON2: C, 61.95; H, 3.90; N, 12.04. Found:
C, 62.16; H, 3.73; N, 11.87. 2-Amino-5-(2-chlorobenzoyl)-
pyridine (15): mp 133.0-133.5 °C; IR (gas phase) 3520, 3421,
mixture was analyzed by GC (detector, FID). The relative rate
of the formation of the products is shown in Table 4.
La ser F la sh P h otolysis. A detailed description of the
experimental setup can be found elsewhere.7a The third and
fourth harmonic (355 and 266 nm) outputs from a Q-switched
Nd:YAG laser (Spectron SL852G-30) were used as excitation
sources. The time duration of the excitation pulse was ca. 6
ns, and the pulse energy was typically 60 mJ . A cw Xe-lamp
(Oriel model 6259, 300 W) was used as a probe light source
for transient absorption measurement. The spectral resolution
was obtained by using SP-275 monochromator (J AMS 27
model 82-49702) after the probe light passed through the
sample solution. A boxcar signal averager (Standard Research
System SR 250) was used in recording the transient signals.
The temporal profile of the transient absorption signal was
monitored by a 500 MHz digital storage oscilloscope (DSO,
Tektronix TDS620B).
1
3074, 1681 cm-1; H NMR (200 MHz, CDCl3) δ 8.38 (d, J )
2.3 Hz, 1H), 7.97 (dd, J ) 8.7, 2.3 Hz, 1H), 7.45-7.34 (m, 4H),
6.51 (d, J ) 8.7 Hz, 1H), 5.18 (br. s, 2H); MS (EI) m/z (rel
intensity) 234 (13, M+ + 2), 232 (38, M+), 197 (19), 121 (100).
Anal. Calcd for C12H9ON2: C, 61.95; H, 3.90; N, 12.04. Found:
C, 62.13; H, 3.89; N, 11.91.
P h otor ea ction of 2-Br om o-N-(2-p yr id in yl)ben za m id e
(3b). The photoreaction of 3b (278 mg, 1 mmol) was performed
for 5 h as described for 1a . GC/MS analysis showed that there
were three products, namely photoreduced (major), photocy-
clized, and photo-Fries-type products. The photoreduced prod-
uct, 11 (82.2 mg, 42%) was purified by column chromatography
(φ 2.2 cm × 25 cm, 70-230 mesh silica gel) with an eluent of
EtOH/CH3CN/CHCl3 ) 1/5/15: mp 80-81 °C (lit.12a mp 80-
83 °C, lit.12b mp 82-84 °C); 1H NMR (200 MHz, CDCl3) δ 9.28
(br s, 1H), 8.41 (dd, J ) 9.3, 0.9 Hz, 1H), 8.10 (dt, J ) 4.9, 0.9
Hz, 1H), 7.93 (dt, J ) 6.4, 1.7 Hz, 1H), 7.74 (dt, J ) 1.5, 7.9
Hz, 1H), 7.59-7.42 (m, 3H), 7.01 (ddd, J ) 7.3, 3.8, 0.9 Hz,
1H); MS (EI) m/z (rel intensity) 198 (12, M+), 169 (53), 105
(100). Anal. Calcd for C12H10ON2: C, 72.71; H, 5.08; N, 14.13.
Found: C, 72.71; H, 5.05; N, 14.06.
Sample solutions were prepared by dissolving the reactants
in acetonitrile with or without tetramethylammonium chloride,
and the concentration of the solution was adjusted to be 0.5-
1.5 in absorbance at 266 nm. The experiment of the temporal
profile with DSO was performed in the same concentration of
1a in acetonitrile without tetramethylammonium chloride
(insets in Figure 4). The sample solution was circulated from
a reservoir (3 L in volume) to the fluorometer quartz cuvette
of 10 mm in path length (Flow type, Helma QS 1.0) to reduce
the effect of the accumulation of the product and dissociation
of the reactant in the photolysis cell (Supporting Information).
The transient absorption spectra for chlorine in pyridine was
measured with the experimental setup, shown in the Support-
ing Information. The method for the transient absorption is
the same as above, except that chlorine is saturated into
pyridine solution and the third harmonic (355 nm) laser was
used for the photolysis.23
P h otor ea ction of 2-Ch lor o-N-m eth yl-N-(4-p yr id in yl)-
ben za m id e (4). The photoreaction of 4 (110 mg, 0.4 m mole)
was performed for 3 h as described for 1a . TLC analysis
showed that there was a photocyclized product, 5-(methyl)-
benzo[c][1,6]naphthyridin-6(5H)-one (16), in high yield (85%,
mp 174-175 °C); UV(λmax in acetonitrile) 325 nm (ꢀ ) 6.25 ×
En er getics. Excitation spectra were obtained by scanning
the excitation wavelength of light for the acetonitrile solution
of 1a (1.0 × 10-4 M) and measuring the fluorescence intensity
at 342 nm (emission maximum). The fluorescence spectra was
obtained by exciting the acetonitrile solution of 1a (1.0 × 10-4
M) with 247-nm light and scanning the emission wavelength
(Supporting Information). The phosphorescence spectra of 1a
was obtained in acetonitrile matrix with a luminescence
spectrophotometer (Perkin-Elmer LS-50). The onset and the
maximum of the phosphorescence are 363 and 425 nm,
respectively.
103 L/mol‚cm); IR (CHCl3) 3071, 1663 cm-1 1H NMR (400
;
MHz, DMSO-d6) δ 8.58 (s, 1H), 7.62 (d, J ) 8.0 Hz, 1H), 7.57
(d, J ) 6.0 Hz, 1H), 7.31 (d, J ) 8.0 Hz, 1H), 6.83 (t, J ) 8.0
Hz,), 6.66 (t, J ) 7.5 Hz), 6.47 (d, J ) 6.0 Hz), 2.62 (s, 3H);
MS (EI) m/z (rel intensity) 210 (100, M+), 181 (30), 154 (7).
Anal. Calcd for C13H10O1N2: C, 74.27; H, 4.80; N, 13.32.
Found: C, 74.17; H, 4.94; N, 12.94.
Kin etics. Mea su r em en t of Qu a n tu m Yield . The inten-
sity of a Xe lamp at certain wavelengthes was measured by
using standard ferrioxalate actinometry. Acetonitrile solutions
of halobenzamide 1a , 2a , 3a , and 4 (1.2 × 10-4 M) under argon
or oxygen were irradiated by a Xe lamp at 270, 278, 282, and
250 nm for 5, 10, 6, and 5 min, respectively, whose intensities
were 3.2, 4.5, 5.1, and 1.0 × 1015 quanta/s, respectively. The
formation of the benzo[c]naphthyridinones are measured by
the UV absorption changes at 322 (for 1a ), 340 (for 2a ), 334
(for 3a ), and 325 nm (for 4), respectively. The quantum yields
are shown at Tables 2 and 3.
The sensitizing behaviors of 1a with triplet sensitizers such
as acetone, acetophenone, and benzophenone were examined.
The acetonitrile solution of 1a (1 mL, 1.0 × 10-3 M) with 1
mL of acetonitrile solution of acetone (1.0 × 10-2 M), acetophe-
none (6.6 × 10-3 M), or benzophenone (3.3 × 10-3 M) in a 3
mL UV cell was deaerated with argon for 20 min and then
irradiated for 2 h with monochromatic light (for acetone,
acetophenone, and benzophenone, 325 ( 10 nm) at which only
the sensitizer absorbed. The relative rate of the sensitizing
reaction is shown in Table 6.
For Stern-Volmer plots, the following procedure was per-
formed: 2 mL of stock acetonitrile solution of 1a (2.5 × 10-3
M, or 2a ) and 80 µL of 0.1 N NaOH aqueous solution were
transferred into a 25 mL volumetric flask with 0, 0.1, 0.2, 0.3,
0.4, 0.5, and 0.6 mL of 0.1 M isoprene acetonitrile solution,
respectively, and diluted to 25 mL with acetonitrile. The 3 mL
of the solution was put into UV cuvette, deaerated with argon,
and irradiated with monochromatic light at 270 nm for 10 min.
The absorption change at 336 nm was monitored. The plot of
Φo/Φ vs the concentration of isoprene yielded a straight line
Ack n ow led gm en t. This work was supported by the
Brain Korea 21 project in 2001.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures for synthesis of 2-halo-N-pyridinylbenzamide (1a , 2a ,
3a , 1b, 2b, 3b, 1c, 4); Stern-Volmer plot of the intramloecular
photocyclization of 1a using the triplet quencher isoprene;
excitation and emission spectra of 1a in acetonitrile; experi-
mental setup for the measurement of the transient absorption
spectra. This material is available free of charge via the
Internet at http://pubs.acs.org.
with an intercept of unit. The KQτ value was 194 M-1
.
16
Assuming KQ ) 6.4 × 109 M-1 s-1
,
the lifetime of the triplet
state of 1a is 30 ns (lower limit).
Rela tive Ra te of P h otocycliza tion . Ten mL of 1.0 mM
of 1a in several solvents or in the solvent containing several
reagents such as methyl methacrylate, Na2CO3, or NaOH was
transferred into 15 mL quartz vessel and then deaerated with
nitrogen for 20 min. After irradiation of the solution with
monochromatic light and its treatment with NaOH for becom-
ing slightly basic medium, the product formed in the reaction
J O001470E
(23) The experiment for the detection of the n-complex of chlorine
radical with pyridine should be carried out under a good hood system.