Unusual 1,4-addition of 2-pyridyl carboxylates to benzynes: A convenient route to 1-(2-acylphenyl)-2-pyridones

Full text of DOI:10.1021/jo010162t

3646
J . Org. Chem. 2001, 66, 3646-3649
Sch em e 1
Un u su a l 1,4-Ad d ition of 2-P yr id yl
Ca r boxyla tes to Ben zyn es: A Con ven ien t
Rou te to 1-(2-Acylp h en yl)-2-p yr id on es
Dinesh Kumar Rayabarapu, Kanak Kanti Majumdar,
Thota Sambaiah, and Chien-Hong Cheng*
Department of Chemistry, Tsing Hua University,
Hsinchu, Taiwan 300
chcheng@mx.nthu.edu.tw
Received February 9, 2001
The chemistry of benzyne has been well incorporated
into the arsenal of synthetic chemistry, and today it is
accepted as a valuable addition to synthetic design.1 This
unstable intermediate exhibits a wide range of reactivity
including electrophilic attack,2 dimerization, and tri-
merization3 as well as [2 + 2] and [4 + 2] cycloadditions4,5
with enes or dienes. One of these reactions receiving
considerable attention is the reaction with 2-pyridones
that shows interesting regio- and chemoselectivity.6
When benzyne is treated with 1-substituted-2-pyridones
only cycloaddition products7,8 are observed, whereas
unsubstituted 2-pyridones provide both [4 + 2] cyclo-
addition and Micheal type addition products (Scheme
1).6,9 In the latter case, both N- and O-arylation take place
to yield 1-phenyl-2-pyridone and 2-phenoxypyridine,
respectively, because of the tautomeric nature of 2-pyri-
dones. These interesting observations raise the question
whether a pure tautomer of 2-pyridones will react with
benzyne to give any addition products. 2-Pyridyl car-
boxylates 2, which can be prepared in good yield as pure
isomers, may be considered as tautomers of the corre-
sponding N-acyl 2-pyridones. In this paper, we wish to
report for the first time the addition chemistry of 2-
pyridyl carboxylates with benzynes. The reaction displays
an unprecedented 1,4-addition of 2-pyridyl carboxylate
to benzyne at 1,2-positions. This new addition reaction
offers a simple and mild method for the introduction of
an amide and a carbonyl to an aromatic ring at ortho
positions.
2-Pyridyl acetate (2a ) was prepared in a pure tauto-
meric form from 2-pyridone and acetyl chloride in the
presence of potassium carbonate in acetone. This product
was identified by comparing the spectral data with those
reported in the literature.10 The reaction of 2-pyridyl
acetate (2a ) with benzyne, generated in situ from isoamyl
nitrite and anthranilic acid, proceeds smoothly to give
1-(2-acetylphenyl)-2-pyridones (3a ) in 58% yield. The
product is fully characterized by its spectral data. The
presence of an R,â-unsaturated lactam group is evidenced
by the observation of a υCO absorption approximately at
1664 cm-1 in the IR spectrum and the resonance at
around 162 ppm in the 13C NMR spectrum. The coupling
(1) For reviews, see: (a) Heaney, H. Chem. Rev. 1962, 62, 81. (b)
Fields, E. K. Org Chem. (N. Y.) 1973, 26, 449. (c) Barton, D. H. R.,
Ollis, W. D. In Comprehensive Organic Chemistry; Barton, D. H. R.,
Ollis, W. D., Eds.; Pergamon: Oxford, 1979; Vol. 1, p 477. (d) For
innovative method to generate benzyne, see: Himeshima, Y.; Sonoda,
T.; Kobayashi, H. Chem. Lett. 1983, 1211. Shankaran, K.; Snieckus,
V. Tetrahedron Lett. 1984, 27, 2827. (e) Winling, A.; Russell, R. A. J .
Chem. Soc., Perkin Trans. 1 1998, 3921. (f) Kelly, T. R.; Sestelo, J . P.;
Tellitu, I. J . Org. Chem. 1998, 63, 3655.
(2) (a) Hart, H. In The chemistry of Triple-Bonded Functional
Groups, Supplement C2; Patai, S., Ed.; Wiley: Chichester, 1994; Ch.
18. (b) Gilchrist, T. L. In The chemistry of Functional Groups,
Supplement C2; Patai, S., Ed.; Wiley: Chichester, 1983; Ch. 11. (c)
Huisgen, R.; Sauer, J . Angew. Chem. 1960, 72, 91. (d) Simmons, H. E.
1
pattern and the number of signals in the H NMR are in
agreement with a 1,2-disubstituted benzene derivative
of the product. The present reaction may be viewed as a
1,4-addition of 2-pyridyl acetate to the carbon-carbon
triple bond of benzyne leading to a disubstituted benzene
derivative. The reaction involves the formation of a new
C-N and C-C bonds with the cleavage of a C-O bond.
To the best of our knowledge, it is the first time that 1,4-
addition of a 2-pyridyl carboxylate to an unsaturated
species is reported. In addition, there are very few
examples of addition to benzyne that resulted in the
formation of disubstituted product.11
In view of the novelty and potential of this reaction
for the synthesis of aromatic compounds, we decided to
investigate this 1,4-addition reaction of 2-pyridyl car-
boxylates to benzyne further in details. 2-Pyridyl car-
boxylates were synthesized according to the procedures
similar to that for 2a by treating the corresponding acid
J
Org. Chem. 1960, 25, 691. (e) Roberts, J . D.; Semenow, D. A.;
Simmons, H. E.; Carlsmith, L. A. J . Am. Chem. Soc. 1956, 78, 601. (f)
Aly, A. A.; Mohamed, N. K.; Hassan, A. A.; Mourad, A. F. E.
Tetrahedron 1999, 55, 1111.
(3) Wittig, G.; Pohmer, L. Chem. Ber. 1956, 89, 1334.
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Academic: New York, 1967; p 200. (b) Stevens, R. V.; Bisacchi, G. S.
J . Org. Chem. 1982, 47, 2393. (c) Hart, H.; Takehira, Y. J . Org. Chem.
1982, 47, 4370. (d) Carre, M. C.; Gregoire, B.; Caubere, P. J . Org. Chem.
1984, 49, 2050. (e) Cossu, S.; De Lucchi, O. Tetrahedron 1996, 52,
14247. (f) Escudero, S.; Dolores, P.; Guitian, E,; Castedo, L. Tetra-
hedron Lett. 1997, 38, 5375.
(5) Wittig, G.; Niethammer, K. Chem. Ber. 1960, 93, 944. (b) Wittig,
G.; Behnisch, W. Chem. Ber. 1958, 91, 2358. (c) Wittig, G.; Knauss, E.
Chem. Ber. 1958, 91, 895. (d) Wittig, G.; Ludwig, R. Angew Chem. 1956,
68, 40.
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Bull. 1985, 33, 2313.
(7) (a) Belkacemi, D.; Malpass, J . R. Tetrahedron 1993, 49, 9105.
(b) Mariano, P. S.; Huesmann, P. L.; Beamer, R. L.; Mariano, D. D.
Tetrahedron 1978, 34, 2617.
(8) (a) Kato, H.; Fujita, R.; Hongo, H.; Tomisawa, H. Heterocycles
1979, 12, 1. (b) Sliwa, W. Heterocycles 1980, 14, 1793 and references
therein.
(9) (a) Kuzuya, M.; Mano, E.; Adachi, M.; Noguchi, A.; Okuda, T.
Chem. Lett. 1982, 475.
(10) (a) Kim, S.; Lee, J . I. J . Org. Chem. 1983, 48, 2608. (b) Hebel,
D.; Rozen, S. J . Org. Chem. 1991, 56, 6298. (c) Hebel, D.; Rozen, S. J .
Org. Chem. 1991, 53, 1123. (d) Rozen, S.; Hebel, D.; Zamir, D. J . Am.
Chem. Soc. 1987, 109, 3789. (e) Usami, K.; Isobe, M. Tetrahedron 1996,
52, 12061.
(11) (a) Hart, F. A. J . Chem. Soc. 1960, 3324. (b) Witting, G.; Benz,
E. Chem. Ber. 1959, 92, 1999. (c) Kakusawa, N.; Sakamoto, K.; Kurita,
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Hayashi, T.; Masumura, M. Chem. Lett. 1980, 1133.
10.1021/jo010162t CCC: $20.00 © 2001 American Chemical Society
Published on Web 04/26/2001

Notes
J . Org. Chem., Vol. 66, No. 10, 2001 3647
Sch em e 2
Sch em e 3
Sch em e 4
Ta ble 1. Rea ction of Ben zyn e w ith 2-P yr id yl
Ca r boxyla tes a n d 2-P yr id yl Ca r bon a tes in
Dich lor om eth a n e-Aceton e Solu tion
tive inductive effect of the aryl group favors 1,4-addition
of 2-pyridyl carboxylate.
The present methodology was further extended to
2-pyridyl carbonates, prepared by the reaction of alkyl
chloroformates with 2-pyridone via an analogous proce-
dure for the synthesis of 2-pyridyl carboxylates 2a -f.
Thus, treatment of methyl (2-pyridyl) carbonate (2g) with
benzyne under similar conditions for 1,4-addition of 2a -f
afforded 3g in 64%. Other 2-pyridyl carbonates 2h -j also
reacted successfully with benzyne to give the correspond-
ing addition products 3h -j, respectively, in moderate
yields (Table 1, entry 8-10). The structures of all
products were also confirmed by their IR, 1H and 13C
NMR, and low- and high-resolution mass spectral data.
To unambiguously determine the structures of this series
of products, the crystal structure of 3g was determined
by X-ray diffraction methods.
The mechanism for this surprising 1,4-addition of
2-pyridyl carboxylate (or carbonate) to benzyne is not
entirely clear. Based on the electrophilic nature of the
benzyne moiety, we proposed that nucleophilic attack
through the nitrogen atom of the pyridyl group at
benzyne initiates the addition reaction. Back attack of
the resulting carbon anion at the carbonyl carbon of
2-pyridyl carboxylate leads to the cleavage of the ester
bond and the formation of the final N-substituted 2-
pyridone (Scheme 3). A concerted pathway via a six-
membered cyclic transition state with substantial charge
redistrubution such as that shown in Scheme 4 leading
simultaneously to the C-O bond cleavage and new C-N
bond formation also cannot be excluded entirely.
One typical way to prove benzyne as an intermediate
reactant is to incorporate substituents to the aromatic
ring of anthranilic acid. Thus we have chosen two
isomeric anthranilic acids, 3-methylanthranilic acid (4a )
and 6-methylanthranilic acid (4b), for 1,4-addition with
compound 2a . Under the reaction conditions, both sub-
strates should provide the same intermediate 5, and we
should obtain the same product(s) in both cases. Con-
sistent with our anticipation, in both cases only product
6a was obtained (Scheme 5). The structure of 6a was
determined by spectroscopic measurements and further
confirmed by single-crystal X-ray diffraction. This result
strongly supports the formation of intermediate benzyne
in this reaction. In principle, the reaction of 2a with the
a
Isolated yields.
chlorides with 2-pyridones in the presence of potassium
carbonate in acetone. The 1,4-addition of 2 to benzyne
was carried out in a refluxing dichloromethane solution
consisting of 2 and isoamyl nitrite. Anthranilic acid in
acetone was added slowly. The procedure was employed
for the addition of 2b-f with benzyne. In all cases, the
1,4-addition products 3b-f were isolated (Scheme 2).
The results of these reactions are shown in Table 1.
Moderate to good yields (48-74%) were obtained, espe-
cially when 2-pyridyl substituted benzoates 2b-d were
used. The compounds were isolated, in most cases, as
stable solids at room temperature after column chroma-
tography. The yield is sensitive to the addition rate of
anthranilic acid. In all cases some starting 2-pyridyl-
substituted benzoates were recovered, and a side product
acridone was observed. The latter was frequently pro-
duced from the reaction of benzyne with anthranilic acid
during the generation of benzyne.12 The reaction of
benzyne with 2-pyridyl-substituted benzoates gave better
yields than with 2-pyridyl acetate, suggesting that nega-
(12) Sheinin, E. B.; Wright, G. E.; Bell, C. L.; Bauer, L J . Heterocycl.
Chem. 1968, 5, 859 and references therein.

3648 J . Org. Chem., Vol. 66, No. 10, 2001
Notes
Sch em e 5
7.73 (1H, dd, J ) 8.2 Hz, J ) 1.2 Hz); 13C NMR (CDCl3, 75 MHz)
δ 28.3, 106.1, 121.4, 127.9, 128.2, 128.8, 132.3, 136.9, 137.7,
138.0, 140.3, 162.1, 199.0; HRMS calcd for C13H11NO2 213.0790,
found 213.0791.
unsymmetrical benzyne 5 should provide an isomeric
mixture 6a and 6b. To our surprise, only a single
regioisomer 6a from both reactions was isolated, indicat-
ing the addition is completely regioselective. The steric
hindrance imparted by the methyl group of phenyl ring
likely dictates the observed regioselectivity.
In conclusion, we have observed for the first time the
1,4-addition of 2-pyridyl carboxylate to benzyne to give
1-(2-acylphenyl)-2-pyridones. The methodology offers a
simple and mild method for the introduction of an amide
and a carbonyl functionality to an aromatic ring at ortho
positions. The reactivity of 2-pyridyl carboxylate and
carbonate is not completely understood, and further
studies are necessary. Extension of this addition chem-
istry to other electron-withdrawing alkynes and alkenes
is possible. Investigation in this direction is underway.
Similar procedures were employed for the synthesis of 3b-j
and 6a . Important data of these products are shown below.
1-(2-Ben zoylp h en yl)-1,2-d ih yd r o-2-p yr id in on e (3b): mp
) 114-115 °C; IR (KBr) 3068, 1659, 1663; 1H NMR (CDCl3, 300
MHz) δ 6.16 (1H, td, J ) 6.6 Hz, J ) 1.5 Hz), 6.37 (1H, d, J )
9.2 Hz), 7.23 (1H, td, J ) 6.6 Hz, J ) 2.1 Hz), 7.27-7.39 (4H,
m), 7.48 (3H, td, J ) 8.2 Hz, J ) 2.0 Hz), 7.60 (1H, td, J ) 7.8
Hz, J ) 1.6 Hz), 7.80 (2H, dd, J ) 8.2 Hz, J ) 1.6 Hz); 13C NMR
(CDCl3, 75 MHz) δ 105.7, 121.4, 127.8, 128.1, 129.6, 130.2, 131.6,
133.0, 136.4, 136.8, 138.0, 139.1, 140.0, 161.9, 194.8; HRMS calcd
for C18H13NO2 275.0946, found 275.0944.
1-[2-(4-Me t h ylb e n zoyl)p h e n yl]-1,2-d ih yd r o-2-p yr id i-
n on e (3c): mp ) 146-148 °C; IR (KBr) 3051, 1655, 1649; 1H
NMR (CDCl3, 300 MHz) δ 2.35 (3H, s), 6.16 (1H, td, J ) 6.8 Hz,
J ) 1.4 Hz), 6.39 (1H, d, J ) 9.2 Hz), 7.19 (2H, dd, J ) 6.8 Hz,
J ) 1.2 Hz), 7.24 (1H, td, J ) 8.8 Hz, J ) 1.6 Hz), 7.35 (2H, td,
J ) 8.2 Hz, J ) 2.0 Hz), 7.46-7.47 (2H, m), 7.60 (1H, ddd, J )
8.8 Hz, J ) 6.4 Hz, J ) 1.6 Hz), 7.70 (2H, dd, J ) 8.2 Hz, J )
1.7 Hz); 13C NMR (CDCl3, 75 MHz) δ 21.6, 105.6, 121.4, 127.9,
128.1, 128.9, 129.4, 130.4, 131.4, 133.8, 137.2, 138.2, 139.0, 140.0,
144.0, 162.0, 194.6; HRMS calcd for C19H15NO2 289.1103, found
289.1098
Exp er im en ta l Section
P r oced u r e for th e Syn th esis of 2-P yr id yl Ca r boxyla tes
a n d Ca r bon a tes (2). In a 100-mL round-bottom flask consisting
of 2-pyridone (1.90 g, 20 mmol), potassium carbonate (6.91 g,
50 mmol), and acyl chloride (50 mmol) was added dry acetone
(40 mL). The mixture was refluxed with stirring for 4 h. The
reaction mixture was cooled to room temperature and was
filtered through Celite. The filtrate was evaporated under
reduced pressure, and the residue was dissolved in ethyl acetate.
The solution was washed thoroughly with water, and the organic
layer was dried over anhydrous MgSO4. After solvent removal,
the crude product was obtained in 80-90% yield. Further
purification on a silica gel column gave the pure product in about
60-80% yield.
1-[2-(3,4,5-Tr im et h oxyb en zoyl)p h en yl]-1,2-d ih yd r o-2-
p yr id in on e (3d ): mp ) 165 °C; IR (KBr) 3038, 1661, 1639;
1H NMR (CDCl3, 300 MHz) δ 3.80 (6H, s), 3.85 (3H, s), 6.16 (1H,
td, J ) 6.6 Hz, J ) 1.1 Hz), 6.40 (1H, d, J ) 9.1 Hz), 7.05 (2H,
s), 7.24 (1H, dd, J ) 6.6 Hz, J ) 2.3 Hz), 7.32 (1H, dd, J ) 6.6
Hz, J ) 1.5 Hz), 7.38(1H, d. J ) 7.6 Hz), 7.50 (2H, dd, J ) 9.1
Hz, J ) 2.2 Hz), 7.62 (1H, dd, J ) 7.6 Hz, J ) 1.6 Hz); 13C NMR
(CDCl3, 75 MHz) δ 56.2, 60.7, 105.8, 107.7, 121.4, 128.1, 128.2,
129.5, 131.4, 131.5, 136.9, 138.2, 138.9, 140.1, 142.7, 152.7, 162.0,
194.0; HRMS calcd for C21H19NO5 365.1263, found 365.1262.
1-{2-[(E )-3-P h en yl-2-p r op en oyl]p h en yl}-1,2-d ih yd r o-2-
p yr id in on e (3e): mp ) 119-120 °C; IR (neat) 3060, 1663, 1645,
This procedure is similar to those reported previously10 and
the 1H NMR data of 2a and 2b are essentially the same as
1
reported. The H NMR data of compounds 2c-d and 2g-h are
1
included in Supporting Information.
1610; H NMR (CDCl3, 400 MHz) δ 6.18 (1H, td, J ) 6.8 Hz, J
) 1.2 Hz), 6.48 (1H, d, J ) 9.2 Hz), 6.93 (1H, d, J ) 15.6 Hz),
7.23-7.34 (6H, m), 7.43-7.51 (4H, m), 7.54-7.58 (1H, m), 7.66
(1H, dd, J ) 8.0 Hz, J ) 1.6 Hz); 13C NMR (CDCl3, 100 MHz) δ
105.8, 121.4, 124.6, 128.0, 128.4, 128.6, 128.7, 128.9, 130.5, 131.6,
134.2, 137.2, 138.0, 138.5, 140.2, 146.3, 162.0, 192.5; HRMS calcd
for C20H15NO2 301.1103, found 301.1096.
1-[2-(2-Th ien ylca r b on yl)p h en yl]-1,2-d ih yd r o-2-p yr id i-
n on e (3f): mp ) 118-120 °C; IR (KBr) 3074, 1667, 1643; 1H
NMR (CDCl3, 400 MHz) δ 6.22 (1H, td, J ) 6.8 Hz, J ) 1.2 Hz),
6.43 (1H, d, J ) 9.2 Hz), 7.18 (1H, t, J ) 7.0 Hz), 7.33-7.41
(3H, m), 7.50-7.65 (5H, m); 13C NMR (CDCl3, 75 MHz) δ 105.7,
121.3, 128.3, 128.1, 128.2, 128.3, 129.1, 131.5, 135.9, 136.6, 138.2,
138.6, 140.1, 143.0, 161.9, 186.6; HRMS calcd for C16H11NSO2
281.0511, found 281.0502.
Meth yl 2-(2-oxo-1,2-d ih yd r o-1-p yr id in yl)ben zoa te (3g):
mp ) 89 °C; IR (KBr) 3019, 1735, 1658; 1H NMR (CDCl3, 300
MHz) δ 3.72 (3H, s), 6.23 (1H, td, J ) 6.8 Hz, J ) 1.1 Hz), 6.60
(1H, d, J ) 9.2 Hz), 7.22 (2H, dd, J ) 6.8 Hz, J ) 1.1 Hz), 7.27
(1H, dd, J ) 7.7 Hz, J ) 1.1 Hz), 7.40 (1H, ddd, J ) 9.2 Hz, J )
6.5 Hz, J ) 2.2 Hz), 7.49 (1H, td, J ) 7.6 Hz, J ) 1.0 Hz), 7.60
Syn t h esis of 1-(2-Acet ylp h en yl)-1,2-d ih yd r o-2-p yr id i-
n on e (3a ). A solution of anthranilic acid (1.10 g, 0.00802 mol)
in acetone (10 mL) was slowly added by syringe pump over 2 h
to a refluxing solution of 2-pyridyl acetate (1.0 g, 0.00729 mol)
and isoamyl nitrite (1.024 g, 0.00874 mol) in methylene chloride
(30 mL). The solution was further refluxed for 5 h. The brown
solution was washed with 10% hydrochloric acid (2 × 20 mL)
followed by water (2 × 20 mL). The solution was dried over
anhydrous MgSO4, and solvent was reduced under reduced
pressure. The resulting dark brown oil was subjected to column
chromatography over neutral alumina with a mixture of hexane
and ethyl acetate (v/v ) 3/2) as the eluent to give the desired
product in 58% yield. Further recrystallization from dichloro-
methane and hexane gave 3a as colorless crystals. Important
spectral data follow. Mp ) 108 °C; IR (KBr) 3047, 1685, 1664
cm -1; 1H NMR (CDCl3, 400 MHz) δ 2.50 (3H, s), 6.30 (1H, td, J
) 6.6 Hz, J ) 1.2 Hz), 6.60 (1H, d, J ) 9.6 Hz), 7.27 (1H, dd, J
) 6.6 Hz, J ) 1.6 Hz), 7.32 (1H, dd, J ) 7.2 Hz, J ) 2.4 Hz),
7.43 (1H, ddd, J ) 9.6 Hz, J ) 6.6 Hz, J ) 2.0 Hz), 7.52 (1H, td,
J ) 8.2 Hz, J ) 1.6 Hz), 7.62 (1H, td, J ) 7.2 Hz, J ) 1.2 Hz),

Notes
J . Org. Chem., Vol. 66, No. 10, 2001 3649
(1H, dd, J ) 7.7 Hz, J ) 1.3 Hz), 8.05 (1H, dd, J ) 7.6 Hz, J )
1.4 Hz); 13C NMR (CDCl3, 75 MHz) δ 52.1, 105.4, 121.1, 127.9,
128.3, 128.8, 131.1, 133.2, 137.5, 140.0, 140.3, 162.4, 165.0;
HRMS calcd for C13H11NO3 229.0739, found 229.0729.
m), 3.92 (2H, d, J ) 6.8 Hz), 6.21 (1H, td, J ) 6.4 Hz, J ) 1.1
Hz), 6.58 (1H, dt, J ) 9.3 Hz, J ) 1.0 Hz), 7.23 (2H, td, J ) 6.4
Hz, J ) 1.3 Hz), 7.38(1H, ddd, J ) 9.2 Hz, J ) 6.5 Hz, J ) 2.0
Hz), 7.49 (1H, td, J ) 7.8 Hz, J ) 1.5 Hz), 7.62 (1H, td, J ) 7.6
Hz, J ) 1.7 Hz), 8.06 (1H, dd, J ) 7.8 Hz, J ) 1.6 Hz); 13C NMR
(CDCl3, 75 MHz) δ 19.0, 27.5, 71.5, 105.5, 121.5, 121.5, 128.5,
128.9, 129.2, 131.4, 133.2, 137.7, 140.0, 140.4, 162.4, 164.8;
HRMS calcd for C16H17NO3 271.1209, found 271.1201.
1-(2-Acetyl-3-m eth ylp h en yl)-1,2-d ih yd r o-2-p yr id on e (6a ):
mp ) 108-110 °C; IR (KBr) 3014, 1675, 1653; 1H NMR (CDCl3,
300 MHz) δ 2.31 (3H, s), 2.32 (3H, s) 6.16 (1H, td, J ) 6.6 Hz,
J ) 1.2 Hz), 6.53 (1H, d, J ) 9.2 Hz), 7.05 (1H, d, J ) 7.7 Hz),
7.14 (1H, d, J ) 6.6 Hz), 7.24 (1H, d, J ) 7.7 Hz), 7.34 (2H, t, J
) 7.5 Hz), 13C NMR (CDCl3, 75 MHz) δ 19.3, 30.8, 105.7, 121.3,
125.1, 129.7, 131.0, 134.6, 136.7, 138.5, 139.7, 140.3, 162.1, 204.1;
HRMS calcd for C14H13NO2 227.0946, found 227.0943.
Eth yl 2-(2-oxo-1,2-d ih yd r o-1-p yr id in yl)ben zoa te (3h ): mp
1
) 70-71 °C; IR (KBr) 3046, 1727, 1660; H NMR (CDCl3, 400
MHz) δ 1.18 (3H, t, J ) 7.2 Hz), 4.18 (2H, q, J ) 7.2 Hz), 6.23
(1H, td, J ) 6.8 Hz, J ) 1.6 Hz), 6.61 (1H, d, J ) 8.4 Hz), 7.25
(1H, d, J ) 6.8 Hz), 7.28(1H, d, J ) 6.6 Hz), 7.40 (1H, td, J )
8.2 Hz, J ) 2.2 Hz), 7.52 (1H, td, J ) 6.4 Hz, J ) 2.1 Hz), 7.61
(1H, td, J ) 6.6 Hz, J ) 1.6 Hz), 8.07 (1H, d, J ) 6.4 Hz); 13C
NMR (CDCl3, 75 MHz) δ 13.7, 61.2, 105.5, 121.3, 128.4, 128.5,
128.9, 131.4, 133.2, 137.7, 140.1, 140.3, 162.5, 164.8; HRMS calcd
for C14H13NO3 243.0895, found 243.0889.
Bu t yl 2-(2-oxo-1,2-d ih yd r o-1-p yr id in yl)b en zoa t e (3i):
syrupy liquid; IR (neat) 3021, 1722, 1665; 1H NMR (CDCl3, 400
MHz) δ 0.82 (3H, t, J ) 7.2 Hz), 1.22-1.28 (2H, m), 1.45-1.48
(2H, m), 4.08 (2H, t, J ) 6.8 Hz), 6.21 (1H, td, J ) 6.8 Hz, J )
1.2 Hz), 6.59 (1H, d, J ) 9.2 Hz), 7.18 (1H, d, J ) 6.8 Hz), 7.22
(1H, d, J ) 7.2 Hz), 7.36 (1H, ddd, J ) 9.2 Hz, J ) 6.4 Hz, J )
1.6 Hz), 7.47 (1H, td, J ) 7.6 Hz, J ) 2.2 Hz), 7.59 (1H, td, J )
7.2 Hz, J ) 2.0 Hz), 8.03 (1H, d, J ) 7.6 Hz); 13C NMR (CDCl3,
100 MHz) δ 13.6, 19.0, 30.3, 65.3, 105.5, 121.5, 126.4, 128.5,
128.9, 131.5, 133.2, 137.7, 140.1, 140.3, 162.5, 164.9; HRMS calcd
for C16H17NO3 271.1209, found 271.1211.
Ack n ow led gm en t. Financial assistance from Na-
tional Science Council (Grant No: NSC 89-2119-M-007-
010) of the Republic of China is greatly acknowledged.
1
Su p p or tin g In for m a tion Ava ila ble: Copies of H NMR
spectra for compounds 3a -j and 6a and ORTEP plots and
X-ray data of compounds 3g and 6a . This material is available
free of charge via the Internet at http://pubs.acs.org.
Isobu tyl 2-(2-oxo-1,2-d ih yd r o-1-p yr id in yl)ben zoa te (3j):
mp ) 63 °C; IR (KBr) 3029, 1721, 1674; 1H NMR (CDCl3, 300
MHz) δ 0.85 (6H, dd, J ) 6.6 Hz, J ) 4.0 Hz), 1.79-1.88 (1H,
J O010162T