Et3N-induced demethylation-annulation of 3-alkynyl-4-methoxy-2- pyridones and structurally related compounds in the synthesis of furan-fused heterocycles

Article abstract of DOI:10.1021/jo8014038

(Chemical Equation Presented) Various 3-iodo-4-methoxypyridin-2-ones and related pyrone and coumarin derivatives have been demonstrated as readily available precursors of 2-substituted furan-fused heterocycles by means of in situ sequential Sonogashira-acetylide coupling, dealkylation, and regioselective furan annulation reactions. A Et₃N-induced S_N2 process has been established that accounts for the dealkylation process.

Full text of DOI:10.1021/jo8014038

SCHEME 1. Tandem Demethylation-Heteroannulation of
o-Acetylenic Anisoles
Et3N-Induced Demethylation-Annulation of
3-Alkynyl-4-methoxy-2-pyridones and
Structurally Related Compounds in the Synthesis
of Furan-Fused Heterocycles
David Conreaux,† Se´bastien Belot,† Philippe Desbordes,‡
Nuno Monteiro,*,† and Genevie`ve Balme*,†
that initial dealkylation steps may be achieved via nucleophilic
substitution reactions under the reaction conditions to generate
an intermediate o-acetylenic phenoxide, which subsequently
undergoes cyclization (Scheme 1).3,4
ICBMS, Institut de Chimie et Biochimie Mole´culaire et
Supramole´culaire, CNRS UMR 5246, UniVersite´ Lyon 1,
ESCPE Lyon. 43, Bd du 11 NoVembre 1918, 69622
Villeurbanne, France, and Bayer CropScience, 14/20 rue
Baizet, BP9163, 69623 Lyon Cedex 09, France
For instance, Buckle showed in 1985 that lithium iodide was
able to dealkylate (2-methoxyphenyl) ethynes in refluxing 2,4,6-
trimethylpyridine, which resulted in the spontaneous5 formation
of benzo[b]furans.3a More recently, Hsung and co-workers
demonstrated the synthesis of 2-amidobenzofurans via Rh-
catalyzed demethylation-cyclization of o-anisole-substituted
ynamides. It was suggested that adventitious water was likely
the nucleophile that carried out the demethylation supposedly
facilitated by prior complexation of the metal to the o-methoxy
oxygen.3b
balme@uniV-lyon1.fr; monteiro@uniV-lyon1.fr
ReceiVed July 02, 2008
In a previous paper we demonstrated a versatile approach to
3,5-disubstituted 4-methoxypyridin-2-ones through site-selective
Pd-catalyzed cross-coupling reactions. For instance, 3,5-di-
iodopyridin-2-one 1 has been shown to undergo selective Suzuki
coupling reactions at the C-5 position to yield 5-arylpyridin-2-
ones 2, thus leaving the remaining C-3 halide free for further
functionalization.6 We now report that the latter 3-iodopyridin-
2-ones can offer facile access to 7-arylfuro[3,2-c]pyridin-4-ones
3, a rare structural core worthy of evaluation for biological
properties,7 by combining Sonogashira-acetylide coupling,
dealkylation, and furan annulation reactions in a one-pot
operation (Scheme 2).8 We also provide clear evidence for a
Et3N-induced SN2 dealkylation mechanism preceding anionic
cyclization. Also included are applications of the method to other
furan-fused heterocycles of biological relevance.
Various 3-iodo-4-methoxypyridin-2-ones and related pyrone
and coumarin derivatives have been demonstrated as readily
available precursors of 2-substituted furan-fused heterocycles
by means of in situ sequential Sonogashira-acetylide cou-
pling, dealkylation, and regioselective furan annulation
reactions. A Et3N-induced SN2 process has been established
that accounts for the dealkylation process.
The construction of furan-fused derivatives is an important
endeavor in organic chemistry because of the abundance of these
heterocyclic scaffolds in a large number of naturally occurring
and designed molecules endowed with a wide array of biological
properties.1 In this area, the cycloisomerization of acetylenic
compounds containing pendant oxygen functionalities offers a
straightforward and atom-economical access to 2-substituted
fused furans. These reactions generally require transition metal
catalysis and may be viewed as proceeding through intramo-
lecular 5-endo-dig attack of the nucleophilic substituent onto
the coordinated alkynyl moiety.2 However, while extensive work
has been devoted to the cyclization of arylalkynol derivatives,
investigations into the potential utility of arylalkynyl ethers as
furan precursors are rare and have remained limited to the case
of the easily accessible o-acetylenic anisoles. It has been shown
Our research originated from an unexpected observation made
during Sonogashira cross-coupling experiments conducted on
(2) For recent contributions, see:(a) Kundu, N. G.; Pal, M.; Mahanty, J. S.;
De, M. J. Chem. Soc., Perkin Trans. 1 1997, 2815. (b) Arcadi, A.; Cacchi, S.;
Di Giuseppe, S.; Fabrizi, G.; Marinelli, F. Synlett 2002, 453. (c) Aucagne, V.;
Amblard, F.; Agrofoglio, L. A. Synlett 2004, 2406. (d) Robins, M. J.; Barr, P. J.
J. Med. Chem. 2005, 48, 4690. (e) Li, X.; Chianese, A. R.; Vogel, T.; Crabtree,
R. H. Org. Lett. 2005, 7, 5437. (f) Belting, V.; Krause, N. Org. Lett. 2006, 8,
4489. (g) Venkataraman, S.; Barange, D. K.; Pal, M. Tetrahedron Lett. 2006,
47, 7317.
(3) (a) Buckle, D. R.; Rockell, C. J. M. J. Chem. Soc., Perkin Trans. 1 1985,
2443. (b) Oppenheimer, J.; Johnson, W. L.; Tracey, M. R.; Hsung, R. P.; Yao,
¨
P.-Y.; Liu, R.; Zhao, K. Org. Lett. 2007, 9, 2361. See also: (c) Godt, A.; Unsal,
¨
O.; Roos, M. J. Org. Chem. 2000, 65, 2837. (d) Colobert, F.; Castanet, A.-S.;
Abillard, O. Eur. J. Org. Chem. 2005, 3334.
(4) For general reviews on dealkylation of ethers, see:(a) Ranu, B. C.; Bhar,
S. Org. Prep. Proced. Int. 1996, 28, 371. (b) Tiecco, M. Synthesis 1988, 749.
(c) Maercker, A. Angew. Chem., Int. Ed. Engl. 1987, 26, 972. (d) Bhatt, M. V.;
Kulkarni, S. U. Synthesis 1983, 249.
(5) 2-Alkynylphenols are known to undergo facile cycloisomerization under
alkaline conditions. For a leading reference, see: Arcadi, A.; Cacchi, S.; Del
Rosario, M.; Fabrizi, G.; Marinelli, F. J. Org. Chem. 1996, 61, 9280.
(6) Conreaux, D.; Bossharth, E.; Monteiro, N.; Desbordes, P.; Vors, J.-P.;
Balme, G. Org. Lett. 2007, 9, 271.
† Universite´ Lyon 1.
‡ Bayer CropScience.
(1) For recent illustrations, see the following reviews:(a) McGuigan, C.;
Balzarini, J. AntiViral Res. 2006, 71, 149. (b) Kim, S.; Salim, A. A.; Swanson,
S. M.; Kinghorn, A. D. Anti-Cancer Agents Med. Chem. 2006, 6, 319. (c) Piggott,
M. J. Tetrahedron 2005, 61, 9929. (d) Santana, L.; Uriarte, E.; Roleira, F.;
Milhares, N.; Borges, F. Curr. Med. Chem. 2004, 11, 3239. (e) McCallion, G. D.
Curr. Org. Chem. 1999, 3, 67.
(7) The related, naturally occurring 7-phenyldihydrofuro[3,2-c]pyridin-4-ones
have been the focus of recent attention:(a) Snider, B. B.; Che, G Org. Lett. 2004,
6, 2877. (b) Clive, D. L. J.; Huang, X. J. Org. Chem. 2004, 69, 1872.
10.1021/jo8014038 CCC: $40.75
Published on Web 10/03/2008
2008 American Chemical Society
J. Org. Chem. 2008, 73, 8619–8622 8619

SCHEME 2. Access to Furo[3,2-c]pyridin-4-ones via
Site-Selective Functionalization of 3,5-Diiodopyridin-2-ones
SCHEME 3. Et3N-Induced Demethylation of
4-Methoxy-pyridin-2-ones
TABLE 1. Synthesis of 2-Substituted Furo[3,2-c]pyridin-4-onesa
refluxing Et3N/MeCN (2:1) for 140 h (Scheme 3).10 Further-
more, indication that Et3N was capturing the labile methyl group
via SN2 displacement prior to cyclization came from the
observation that the methyl group of a 3,5-diarylpyridone lacking
the triple bond was cleaved by triethylamine. For instance, 3,5-
bisarylic 4-methoxy-1-methylpyridin-2-one 5 was treated by
Et3N in MeCN at 80 °C for 140 h. After solvent removal under
vacuum, the crude reaction mixture was subjected to fraction-
ation on silica gel to give 4-hydroxypyridin-2-one 6 (35% yield)
and recovered 5 (48%) (Scheme 3).11 In another experiment,
the crude reaction mixture was dissolved in chloroform and
extracted with water. The aqueous phase was then concentrated
to dryness to leave a residual colorless gum containing an
unstable pyridone derivative whose structure was tentatively
assigned to triethylmethyl ammonium (TEMA) enolate 7 by
NMR and mass spectroscopy.12
R1/R2
R3
product(s)/yield (%)b
1
2
3
4
5
6
7
p-OMePh/Me (2a)
p-OMePh/Bn (2b)
p-OMePh/Bn (2b)
p-OMePh/Me (2a)
Ph/Me (2c)
p-CO2MePh/Me (2d)
p-CO2MePh/Me (2d)
Ph
Ph
3a/63
3b/75
3c/69
3d/37c
3e/59c
3f/56
(4a/22)
(4b/<5)
(4c/<5)
(4d/23)
(4e/37)
(4f/11)
(4g/<5)
p-CO2MePh
SiMe3
Ph
p-OMePh
Ph
3g/75
a All reactions were run on 0.4 mmol of the 3-iodopyridin-2-ones in 3
mL of Et3N:DMF (2:1). b Isolated yields (single runs). Numbers in
parentheses refer to yields of recovered 3-alkynylpyridin-2-one
intermediates 4. c Reaction performed in Et3N/MeCN.
The capability of tertiary aliphatic amines to effect the
cleavage of methyl ethers through nucleophilic displacement
on the methyl group has been known for a long time. However,
this interesting feature has not yet been developed into a
synthetically useful dealkylation method. Indeed, the effective-
ness of such a process generally requires drastic conditions and
has been demonstrated mainly in the case of highly electron-
deficient aromatics such as picryl ethers.13,14 In light of the
previous observations, we may propose the plausible, general
mechanistic pathway described in Scheme 4 to explain the
demethylation-cyclization process. Thus, nucleophilic displace-
ment of the methyl group by triethylamine would generate a
delocalized triethylmethyl ammonium enolate 8. The latter
would then undergo regioselective anionic 5-endo-dig cycliza-
tion to form the anionic furan intermediate 9, which upon
capture of a proton from water15 would furnish the desired
furo[3,2-c]pyridin-4-one together with the corresponding qua-
ternary ammonium salt TEMA-OH (10). Interestingly, formation
of the isomeric furo[3,2-c]pyridin-2-ones 11 was not observed.16
5-(4-methoxyphenyl)-pyridin-2-one 2a. When the latter was
reacted with phenylacetylene for reaction times longer than
normally required to effect the cross-coupling reaction under
classical Sonogashira conditions (cat. PdCl2(PPh3)2, cat. CuI,
Et3N/MeCN, 50 °C),9 small amounts of a side product, identified
as furo[3,2-c]pyridin-4-one 3a, were isolated in addition to the
expected coupling product 4a. Optimization of this model
reaction required more forcing conditions than those described
above and particularly higher temperatures (80 °C). DMF could
also be used as a cosolvent to give essentially the same results.
These new reaction conditions were found also to be effective
for the synthesis of diversely substituted furopyridin-2-ones in
moderate to good yields. 5-Aryl-3-iodopyridin-2-ones with both
electron-donating and electron-withdrawing groups at the para
position of the aromatic ring gave satisfying results. The
acetylenic partners have also been expanded successfully to
electron-rich and electron-poor aryl acetylenes, as well as TMS-
acetylene (Table 1).
Further experiments have provided valuable insight into the
mechanism of the furan-forming reaction. It was found that the
process does not require metal catalysis and that Et3N, used as
cosolvent, was the sole reagent involved in the heteroannulation
process. For instance, furopyridinone 3a was isolated in 67%
yield upon simple heating of 3-alkynylpyridin-2-one 4a in
(10) It is worthy of note that the demethylation-cyclization reaction time
may be significantly shortened by using microwave-induced heating. In a
preliminary experiment a solution of alkynylpyridone 4b in Et3N/DMF (2:1)
was submitted to microwave irradiation (CEM Discover apparatus; settings
120°C, 150W) during 6 h to give the corresponding furan derivative 3b in 81%
isolated yield.
(11) The slow convertion rate may be explained by increased steric hindrance
around the methoxy group.
(12) See Supporting information.
(8) So far, only one example of a similar process has been reported in the
literature which refers to the formation in low yield of a furo[3,2-c]quinolin-4-
one during the reaction of a 3-bromo-4-methoxyquinolin-2-one with a copper
acetylide: Gaston, J. L.; Greer, R. J.; Grundon, M. F. J. Chem. Res., Synop.
1985, 135.
(9) The coupling reaction is normally achieved in less than 16 h at 60°C to
give 4a in up to 81% isolated yield.
(13) (a) Burwell, R. L Chem. ReV. 1954, 615. For a more recent leading
reference, see: (b) Strauss, M.; Torres, R. J. Org. Chem. 1989, 54, 756.
(14) Scarce examples of nucleophilic O-dealkylations have also been reported
to occur in the presence of primary and secondary aliphatic amines under high
reaction temperatures (150-200°C):(a) Nishioka, H.; Nagasawa, M.; Yoshida,
K. Synthesis 2000, 243. (b) Shcherbakova, I.; Balandrin, M. F.; Fox, J.; Ghatak,
A.; Heaton, W. L.; Conklin, R. L. Bioorg. Med. Chem. Lett. 2005, 15, 1557.
8620 J. Org. Chem. Vol. 73, No. 21, 2008

marins and coumestans.19 Interestingly, reaction of iodocoumarin
15 with phenylacetylene in MeCN at 60 °C under Sonogashira
conditions did not allow isolation of the acetylenic coumarin
16 but instead led directly to the desired furocoumarin 17 within
15 h (70% isolated yield). It is worthy of note that the
Sonogashira coupling product 16 may be obtained in up to 76%
isolated yield by performing the coupling reaction at room
temperature.
SCHEME 4. Plausible Mechanism for the Et3N-Induced
Dealkylation-Cyclization of
3-Alkynyl-4-alkoxypyridin-2-ones
This preliminary result holds promise as an efficient, straight-
forward entry to furo[3,2-c]coumarins that compares favorably
to previous methods reported in the litterature.20 Again, Et3N
was found to be responsible for the demethylation step.
However, in contrast to what was observed in the pyridone
series, additional experiments suggested that copper catalysis
was occurring in the cyclization step. Indeed, when acetylenic
coumarin 16 was heated at 60 °C for 24 h in a mixture of Et3N/
MeCN, furocoumarin 17 was produced in only 15% yield. The
main reaction product turned out to be the stable quaternary
ammonium enolate intermediate 18, which could be isolated
by extraction into water and characterized by FT-IR, NMR, and
mass spectroscopy.12 On the other hand, when the same reaction
was performed in the presence of 10 mol % CuI, the desired
furocoumarin was isolated in 69% yield after 15 h reaction time.
A reasonable mechanism for the Cu-catalyzed furan formation
would involve coordination of the triple bond by CuI21 followed
by nucleophilic attack of the enolate, forming copper intermedi-
ate 19. The latter would be protonated by water present in the
system as contaminant, regenerating CuI and producing the furan
derivative (Scheme 6).
SCHEME 5. One-Pot Synthesis of Furopyrone and
Furocoumarin Derivatives
In conclusion, we have shown that 3-iodopyridin-2-ones can
give easy access to 2-substituted furan derivatives through in
situ sequential Sonogashira-acetylide coupling, dealkylation, and
furan annulation reactions. As for the dealkylation process, we
have provided evidence for a Et3N-induced SN2 mechanism.
The successful participation of structurally related compounds
like pyrone and coumarin derivatives prefigures future exten-
sions of this chemistry to the synthesis of other bis-heterocyclic
compounds of interest. Further work will take into account the
necessity of shortening reaction times in the pyridone series
for better efficiency, most probably by using microwave
catalysis.
Next, the synthetic potential of the cascade coupling-
cyclization methodology presented above led us to query
whether other heterocyclic compounds structurally related to
the 3-iodo-4-methoxypyridin-2-ones would behave in the same
manner. We naturally turned our attention to the readily
available 3-iodopyrone derivative 12.17 As a preliminary experi-
ment, the Sonogashira coupling reaction of 12 with pheny-
lacetylene was tested under classical reaction conditions (MeCN,
60 °C, 15 h), which allowed the isolation of 3-alkynyl-2-pyrone
13 in 73% yield (Scheme 5). Gratifyingly, when the same
reaction was run at 80 °C in DMF as cosolvent, complete in
situ conversion of the intermediate alkyne into furo[3,2-c]pyran-
4-one 1418 (82% isolated yield) was achieved in 48 h. Encour-
aged by this interesting result, we then focused on expanding
the protocol to include the easily accessible 3-iodo-4-methoxy-
coumarin 15 owing to the biological importance of furo[3,2-
c]coumarins as well as the structurally related dihydrofurocou-
(18) This structure is rather uncommon but may be found in natural
products: (a) Wang, Y.; Shang, X.-Y.; Wang, S.-J.; Mo, S.-Y.; Li, S.; Yang,
Y.-C.; Ye, F.; Shi, J.-G.; He, L. J. Nat. Prod. 2007, 70, 296. (b) Lee, I.-K.;
Yun, B.-S. Bioorg. Med. Chem. Lett. 2006, 16, 2376.
(19) Furocoumarins:(a) Wang, X.; Nakagawa-Goto, K.; Kozuka, M.; Tokuda,
H.; Nishino, H.; Lee, K.-H. Pharm. Biol. 2006, 44, 116. (b) Mulholland, D. A.;
Iourine, S. E.; Taylor, D. A. H.; Dean, F. M. Phytochemistry 1998, 47, 1641.
Dihydrofurocoumarins: (c) Motai, T.; Kitanaka, S. Chem. Pharm. Bull. 2004,
52, 1215. (d) Lee, Y. R.; Kim, B. S.; Wang, H. C Tetrahedron 1998, 54, 12215.
Coumestans: (e) Poˆc¸as, E. S. C.; Lopes, D. V. S.; da Silva, A. J. M.; Pimenta,
P. H. C.; Leita˜o, F. B.; Netto, C. D.; Buarque, C. D.; Brito, F. V.; Costa, P. R. R.;
Noe¨l, F. Bioorg. Med. Chem. 2006, 14, 7962. (f) da Silva, A. J. M.; Melo, P. A.;
Silva, N. M. V.; Brito, F. V.; Buarque, C. D.; de Souza, D. V.; Rodrigues, V. P.;
Pocas, E. S. C.; Noel, F.; Albuquerque, E. X.; Costa, P. R. R. Bioorg. Med.
Chem. Lett. 2001, 11, 283.
(15) Protonation may occur spontaneously due to the probable presence of
water as contaminant in the system or during workup. When used as solvent,
MeCN may also intervene as a proton source owing to the predictable high
basicity of the furan 2-anion:Shen, K.; Fu, Y.; Li, J.-N.; Liu, L.; Guo, Q.-X.
Tetrahedron 2007, 63, 1568.
(20) In many cases, mixtures of isomeric furo[3,2-c]coumarins and furo[3,2-
b]chromones have been previously obtained:(a) Lee, Y. R.; Suk, J. Y.
Tetrahedron 2002, 58, 2359. (b) Tollari, S.; Palmisano, G.; Cenini, S.; Cravotto,
G.; Giovenzana, G. B.; Penoni, A. Synthesis 2001, 735. (c) Kobayashi, K.;
Sakashita, K.; Akamatsu, H.; Tanaka, K.; Uchida, M.; Uneda, T.; Kitamura, T.;
Morikawa, O.; Konishi, H. Heterocycles 1999, 51, 2881. (d) Lee, Y. R.; Byun,
M. W.; Kim, B. S. Bull. Korean Chem. Soc. 1998, 19, 1080. (e) Lee, Y. R.;
Kim, B. S.; Wang, H. C. Tetrahedron 1998, 54, 12215. For a recent, selective
approach to furo[3,2-c]coumarins, see: (f) Cheng, G.; Hu, Y. Chem. Commun.
2007, 3285.
(16) Previous investigations from the same laboratories have demonstrated
the selective synthesis of furopyridones of type 11 through electrophilic
annulation/dealkylation reactions of 4-alkoxy-3-alkynyl-2-pyridones:(a) Bossharth,
E.; Desbordes, P.; Monteiro, N.; Balme, G Org. Lett. 2003, 5, 2441. (b) Aillaud,
I.; Bossharth, E.; Conreaux, D.; Desbordes, P.; Monteiro, N.; Balme, G. Org.
Lett. 2006, 8, 1113.
(17) Cerezo, S.; Moreno-Man˜as, M.; Pleixats, R. Tetrahedron 1998, 54, 7813.
(21) Yamamoto, Y. J. Org. Chem. 2007, 72, 7817.
J. Org. Chem. Vol. 73, No. 21, 2008 8621

SCHEME 6. Working Mechanism for the Et3N/CuI-Induced
Dealkylation-Cyclization of 3-Alkynylcoumarin 16
7.72-7.75 (m, 2H). 13C NMR (75 MHz, CDCl3): δ 37.5, 55.7,
102.4, 111.0, 114.7, 118.3, 124.8, 125.4, 128.9, 129.2, 130.0, 132.4,
155.3, 157.2, 159.2, 159.7. HRMS (ESI): MH+, 332.1280; calcd
for C21H17NO3, 332.1287.
2-Phenyl-4H-furo[3,2-c][1]benzopyran-4-one 17. A mixture of
3-iodocoumarin 15 (60.4 mg, 0.2 mmol), phenylacetylene (61.3 mg,
0.6 mmol), PdCl2(PPh3)2 (11.2 mg, 0.016 mmol), and CuI (3.0 mg,
0.016 mmol) was dissolved in MeCN (1 mL) and TEA (2 mL) in
a glass tube fitted with a Teflon screw seal. The reactor was flushed
with nitrogen, and the reaction mixture was left to stir at 60 °C for
15 h and then concentrated under reduced pressure. The crude
material so obtained was purified via column chromatography on
silica gel using AcOEt/petroleum ether (1:4) as eluent to give 36.7
mg (70%) of 17 as a solid. Mp 166-168 °C. Spectral properties
(IR, NMR) identical to those reported previously.20f HRMS (ESI):
MH+, 263.0707; calcd for C17H11O3, 263.0708.
Experimental Section
Typical Representative Procedures for Sonogashira-Acetylide
Coupling/Annulation Reactions. 7-(4-Methoxy)phenyl-5-methyl-
2-phenylfuro[3,2-c]pyridin-4(5H)-one 3a. A mixture of 3-iodopy-
ridin-2-one 2a (74.2 mg, 0.2 mmol), phenylacetylene (61.3 mg,
0.6 mmol), PdCl2(PPh3)2 (14.0 mg, 0.02 mmol), and CuI (7.6 mg,
0.04 mmol) was dissolved in DMF (1 mL) and TEA (2 mL) in a
glass tube fitted with a Teflon screw seal. The reactor was flushed
with nitrogen, and the reaction mixture was left to stir at 80 °C for
140 h and then concentrated under reduced pressure. The crude
material so obtained was purified via column chromatography on
silica gel using acetone/CH2Cl2 (1:9) as eluent to give 41.7 mg
(63%) of 3a as a solid. Mp 190-194 °C. IR (KBr): 3059, 1773,
Acknowledgment. This research was assisted financially by
a grant to D.C. from Bayer CropScience and the Centre National
de la Recherche Scientifique. Dr. D. Bouchu is acknowledged
for mass spectrometric analyses and Prof. P. Renaud (University
of Bern) for valuable discussions.
Supporting Information Available: Experimental proce-
dures and characterization data for all compounds and copies
of NMR spectra of furan-fused heterocyclic compounds 3a-g,
14, and 17 and ammonium enolate intermediates 7 and 18. This
material is available free of charge via the Internet at
http://pubs.acs.org.
1
1713, 1656 cm-1. H NMR (300 MHz, CDCl3): δ 3.66 (s, 3H),
3.87 (s, 3H), 7.02 (dd, J ) 6.8 and 2.0 Hz, 2H), 7.24 (s, 1H), 7.25
(s, 1H), 7.30-7.44 (m, 3H), 7.63 (dd, J ) 6.8 and 2.0 Hz, 2H),
JO8014038
8622 J. Org. Chem. Vol. 73, No. 21, 2008