A new synthesis of 4H-1-benzothiopyran-4-ones using (trimethylsilyl)methylenetriphenylphosphorane

Article abstract of DOI:10.1016/S0040-4020(01)00977-2

The reaction of silyl ester of S-acyl(aroyl) thiosalicylic acids 3 with (trimethylsilyl)methylenetriphenylphosphorane 4 in step wise fashion leads to the acylphosphoranes 7, which subsequently undergo intramolecular Wittig cyclization on the thiolester carbonyl to afford the 4H-1-benzothiopyran-4-ones 8 in good to excellent yields.

Full text of DOI:10.1016/S0040-4020(01)00977-2

TETRAHEDRON
Pergamon
Tetrahedron 57 %2001) 9755±9758
A new synthesis of 4H-1-benzothiopyran-4-ones using
ꢀtrimethylsilyl)methylenetriphenylphosphorane
Pradeep Kumarp and Mandar S. Bodas
Division of Organic Chemistry: Technology, National Chemical Laboratory, Pune 411008, India
Received 24 July 2001; accepted 12 October 2001
AbstractÐThe reaction of silyl ester of S-acyl%aroyl) thiosalicylic acids 3 with %trimethylsilyl)methylenetriphenylphosphorane 4 in step
wise fashion leads to the acylphosphoranes 7, which subsequently undergo intramolecular Wittig cyclization on the thiolester carbonyl to
afford the 4H-1-benzothiopyran-4-ones 8 in good to excellent yields. q 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
synthesized either by the condensation of a b-keto ester
with a thiophenol in polyphosphoric acid9 or by the cycli-
zation of a b-substituted cinnamate, derived from the
constituent thiophenol and an appropriate propiolate.10
Recently, 4H-1-benzothiopyran-4-ones were prepared by
the condensation and subsequent acid-induced cyclization
of lithiated intermediates derived either from aceto-
acetanilide,11 C%a),N-benzoylhydrazones or C%a),N-carbo-
alkoxy hydrazones12 with methylthiosalicylate. However,
most of these methods suffer either from harsh reaction
conditions, poor substituent tolerance or from low chemical
yields. Also, some of these methods could not be applied
for the synthesis of many target molecules,13 in particular
methoxy-substituted thio¯avone.14 We now report a con-
venient and ef®cient route to 1-benzothiopyran-4-ones via
intramolecular thiolester carbonyl ole®nation using
%trimethylsilyl) methylenetriphenylphosphorane.
1-Benzothiopyran-4-ones are an important class of hetero-
cycles. They serve as key intermediates for the synthesis of
biologically active compounds.1 As part of our ongoing
program for developing methodologies via intramolecular
Wittig ole®nation and their subsequent application to bio-
logically useful compounds, the phosphacumulene ylides
were envisaged as a versatile reagent offering considerable
opportunities for synthetic manipulations.2 The intra-
molecular Wittig reaction has been extensively employed
as an excellent method for the C±C bond forming process
in the synthesis of natural products.3 In this connection
the mono-and bis%trimethylsilyl)methylenetriphenylphos-
phorane, one of the recent arrivals in the series of organo-
phosphorus reagents, are of special interest.4 Recently, in
our preliminary communication, we have reported a novel
method for the synthesis of chromones via intramolecular
Wittig reaction using %trimethylsilyl)methylenetriphenyl-
phosphorane.5 Further, we have studied and extended the
scope of this methodology for the construction of benzo-
thiopyran ring.
2. Results anddiscussion
Thiosalicylic acid 1 was converted into its S-acyl%aroyl)
derivatives 2 by reaction with corresponding acid chloride
or anhydride. Compound 2 was then treated with tert-butyl-
dimethylsilyl chloride in presence of imidazole to furnish
the corresponding silyl ester 3 in good yields. When a
mixture of compound 3 and %trimethylsilyl)methylene-
triphenylphosphorane4 4 was heated in re¯uxing THF, the
desired 2-substituted, 4H-1-benzothiopyran-4-ones 8 were
obtained in 58±90% yields %Table 1). The conversion of 3
into 8 could be explained by a sequence of reaction as
depicted in Scheme 1. The plausible mechanism can be
visualized as initial acylation of %trimethylsilyl)methylene-
triphenylphosphorane 4 by 3 to the resulting phosphonium
salt 5. There is then migration of the trimethylsilyl group
from C to O followed by the extrusion of silyl ether 6
leading to the acylphosphorane 7, which subsequently
undergoes ring closure via the intramolecular Wittig
While chromones %4H-1-benzopyran-4-ones) have been
extensively investigated regarding their synthesis, their iso-
lation as secondary metabolites, and their potential for broad
spectrum biological activity,6 a little attention has been paid
towards the synthesis and biological evaluation of thio-
chromones %4H-1-benzothiopyran-4-ones).7 These com-
pounds have been prepared and studied for their
biological potential, especially as bacteriocides and anti-
cancer agents.8 In general, 1-benzothiopyran-4-ones are
Keywords: S-acyl%aroy)thiosalicylic acids; %trimethylsilyl)methylenetri-
phenylphosporane; acylphosphorane; intramolecular Wittig cyclization;
thiochromones.
Corresponding author. Tel.: 191-20-5893300; fax: 191-20-5893614;
e-mail: tripathi@dalton.ncl.res.in
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020%01)00977-2

9756
P. Kumar, M. S. Bodas / Tetrahedron 57 ,2001) 9755±9758
Table 1. One-pot synthesis of 2-substituted, 4H-1-benzothiopyran-4-ones
from 3 and 4
No.
1
Substrate
Producta
R.T %h)
16
Yield %%)b
80
2
3
4
5
6
7
8
9
17
18
22
21
25
35
38
30
33
76
90
68
69
60
62
63
65
58
Scheme 1. Reagents and conditions: %a) RCOCl or %RCO)2O, aq. KOH,
08C±room temperature, 0.5 h, 75±80%; %b) TBDMS-Cl, imidazole
%1.5 equiv.), CH2Cl2, 08C±room temperature, 7±8 h, 65±70%; %c) 16±
38 h in THF, re¯ux, 58±90%.
intramolecular Wittig cyclization at re¯ux temperature to
afford the desired product 8a.
The intramolecular Wittig cyclization involving phosphorus
ylide and thiolester carbonyl is general for the preparation of
a variety of thiochromone derivatives. Further, an electron
donating substituent in 3f reduces the rate of intramolecular
Wittig reaction %Table 1, entry 6) and hence a little longer
time is required to complete the reaction affording relatively
low yield of the product 8f. As it can be seen from Table 1,
the steric effect during the Wittig cyclization resulting from
the substitution in aroyl group appears to be more signi®cant
than the electronic factor. Thus, an ortho-substituent such as
the chloro and nitro group in 3g and 3h, respectively and
meta-substituents such as the nitro and methoxy group in 3i
and 3j have pronounced steric hindrance due to their close
proximity to the carbonyl group and hence a longer time is
required to complete the reaction affording relatively low
yields of products 8g±j %Table 1, entries 7±10). It may be
mentioned that the cyclization of cinnamate with an electron
donating substituent such as methoxy by a usual process led
to the formation of the corresponding coumarin instead of
thiochromone.14 Also, the reaction of methoxy substituted
benzenethiol with ethylbenzoylacetate by a conventional
method has been found to give a mixture of the correspond-
ing thio¯avone and isomeric thiocoumarin or only the thio-
coumarin in very low yield.15 In this connection, the present
methodology for 8f and 8j is noteworthy. Some of the
synthesized compounds are precursors for thiochroman-4-
ones, which serve as key intermediates in the syntheses of a
variety of compounds of biological interest.16
10
a
All products were characterized by their satisfactory spectroscopic data.
Yields refer to isolated pure products.
b
reaction on the thiolester carbonyl to afford the desired
thiochromones 8.
With a view to ascertaining the reaction pathway, the
reaction of the silyl ester of S-acetylthiosalicylic acid 3a
with 4 was carried out at different temperature in order to
trap the intermediates formed during reaction. Although the
treatment of 3a with 4 in THF at room temperature did not
show any progress of reaction, the extrusion of silyl ether 6
and formation of the acylphosphorane 7a could be observed
when the reaction was performed at higher temperature
%558C). Interestingly, the acylphosphorane 7a was found
to be stable enough to be isolated and was further charac-
3. Conclusion
1
terized by its satisfactory IR, H NMR and MS spectro-
In summary, we have developed an ef®cient annulation
protocol for a variety of thiochromones via intramolecular
Wittig thiolester carbonyl ole®nation using %trimethylsilyl)-
methylenetriphenylphosphorane. This method offers a more
general and one-pot synthesis of 1-benzothiopyran-4-one.
The protocol developed could be useful particularly in
the synthesis of methoxy-substituted benzothiopyranones.
Further investigations to explore the synthetic potential of
scopic data. Compound 7a on heating in re¯uxing THF
gave the desired 2-methyl-1-benzothiopyran-4-one %8a).
The phosphonium salt 5a could not be isolated presumably
due to its fast rearrangement into the acylphosphorane 7a.
However, the above ®nding indicates that compound 7a
which results from 5a after the cleavage of silyl ether 6,
is one of the intermediates which undergoes subsequent

P. Kumar, M. S. Bodas / Tetrahedron 57 ,2001) 9755±9758
9757
mono- and bis-silylated phosphorus ylides are currently
underway in our laboratories.
solvent was evaporated under reduced pressure and residue
thus obtained was washed several times with petroleum
ether to afford 1.25 g %85%) of suf®ciently pure acylphos-
phorane 7a, which was fully characterized by spectroscopic
and analytical data.
4. Experimental
4.5.1. Compound7a. Oil; IR nmax/cm21 %CHCl3): 1294,
1437, 1480, 1540, 1610, 1705; H NMR %CDCl3) d: 0.89
4.1. General information
1
The solvents were puri®ed by standard procedures before
use; petroleum ether of boiling range 60±808C was used.
Melting points were determined with a Mel-Temp apparatus
and are uncorrected. Infrared spectra were recorded on
%s, 3H), 2.04 %d, 1H, Jˆ14 Hz), 7.27±7.77 %m, 19H). Mass
%EI), m/z %%): M1 454 %1), 440 %1), 277 %10), 224 %3), 215
%40), 201 %78), 152 %35), 107 %25), 75 %100). Anal. Calcd for
C28H23O2PS: C, 74.00; H, 5.10; S 7.04. Found C, 73. 76; H,
5.34; S, 7.34.
1
an ATI MATTSON RS-1 FT-IR spectrometer. H NMR
spectra were recorded on Bruker AC-200 NMR spectro-
meter. The chemical shifts are reported in parts per million
%d) with tetramethyl silane as an internal standard. Mass
spectra were obtained with a Finnigan MAT-1020B-70 eV
mass spectrometer. Elemental analyses were carried on a
Carlo Erba CHNS-O analyzer.
4.6. Procedure for the preparation of 4H-1-benzothio-
pyran-4-ones ꢀ8)
To a solution of compound 3 %50 mmol) in absolute THF
%5 ml) was added under stirring the equimolar amount of
silylated ylide 4 %50 mmol) in THF %5 ml). The reaction
mixture was re¯uxed for the indicated length of time
%Table 1). The reaction was monitored by TLC. After
completion of reaction, the solvent was evaporated and
the residue was puri®ed by column chromatography %pet.
ether/ethyl acetate, 98:2), to afford the product 8, in 58±
90% yields.
4.2. Procedure for S-acylꢀaroyl)thiosalicylic acidꢀ2)
10 g of ice followed by freshly distilled acid chloride or acid
anhydride %10 mmol) were added to an ice-cold solution of
thiosalicylic acid 1 %8 mmol) and potassium hydroxide
%20 mmol) in water %12 ml). The resulting mixture was
stirred vigorously for 0.5 h at room temperature. After the
reaction was complete, the solution was acidi®ed with dil.
HCl and the material, which precipitated out, was ®ltered
and washed with water. Recrystallization of the crude
product from pet. ether/ethyl acetate or hexane gave the
product 2 in 75±80% yield.
4.6.1. 2-Methyl-4H-1-benzothiopyran-4-one ꢀ8a). Color-
less solid; mp 100±1018C %Lit.9 1038C); IR nmax/cm21
%CHCl3): 1400, 1600, 1703; H NMR %CDCl3) d: 2.48 %s,
1
3H), 6.85 %s, 1H), 7.55±7.65 %m, 3H), 8.09±8.39 %m, 1H).
Mass %EI), m/z %%): M1 176 %100), 147 %85), 136 %87).
4.3. Procedure for tert-butyldimethylsilyl ester of
S-acylꢀaroyl)thiosalicylic acidꢀ3)
4.6.2. 2-Ethyl-4H-1-benzothiopyran-4-one ꢀ8b). Oil; IR
n
1
max/cm21 %CHCl3): 1676; H NMR %CDCl3) d: 1.15 %t,
3H, Jˆ8 Hz), 2.62 %q, 2H, Jˆ8 Hz), 6.9 %s, 1H), 7.32±
7.52 %m, 3H), 7.6±8.0 %m, 1H). Mass %EI), m/z %%): M1
190 %20), 167 %40), 149 %100), 136 %35). Anal. Calcd for
C11H10OS: C, 69.44; H, 5.30; S, 16.85. Found C, 69.68;
H, 5.57; S, 17.13.
A solution of compound 2 %10 mmol) and imidazole
%15 mmol) in dichloromethane %5 ml) was cooled to 08C,
and mixture was stirred under nitrogen atmosphere. To the
above solution, was added tert-butyldimethylsilyl chloride
%13 mmol) at 08C and the reaction mixture was stirred at
room temperature under nitrogen atmosphere for 7±8 h.
After the reaction was complete, the reaction mixture was
quenched with saturated solution of ammonium chloride
and extracted with dichloromethane. The organic layer
was separated and dried over anhydrous Na2SO4. The
solvent was evaporated under reduced pressure to give
the product 3 in 65±70% yield, which was used as such
for the next reaction without further puri®cation.
4.6.3. 2-Phenyl-4H-1-benzothiopyran-4-one ꢀ8c). Color-
less solid; mp 1268C %Lit.10a 122±1238C); IR nmax/cm21
%CHCl3): 1600, 1688 1445; H NMR %CDCl3) d: 7.12 %s,
1
1H), 7.49±7.67 %m, 6H), 8.03±8.07 %m, 3H). Mass %EI), m/z
%%): M1 238 %40), 215 %100), 136 %50), 107 %60), 77 %45).
4.6.4. 2-ꢀ40-Nitrophenyl)-4H-1-benzothiopyran-4-one ꢀ8d).
Colorless solid; mp 2528C %Lit.17 250±2528C); IR nmax/cm21
%CHCl3): 1690, 1532, 1215; 1H NMR %CDCl3) d: 6.92±7.05
%m, 3H), 7.51±7.58 %m, 2H), 7.93±8.33 %m, 4H). Mass %EI),
m/z %%): M1 283 %40).
4.4. Preparation of 4
The %trimethylsilyl)methylene triphenyl phosphorane %4)
was prepared following the literature procedure4 from
methylenetriphenylphosphorane and trimethylsilyl chloride.
4.6.5. 2-ꢀ40-Chlorophenyl)-4H-1-benzothiopyran-4-one
ꢀ8e). Colorless solid; mp 187±1898C %Lit.13 189±1908C);
IR nmax/cm21 %CHCl3): 1692, 1540, 1215; 1H NMR
%CDCl3) d: 7.21±7.50 %m, 5H), 7.84±7.97 %m, 4H). Mass
%EI), m/z %%): M1 272 %30), 244 %35), 139 %100).
4.5. Procedure for the preparation of 7a
To a solution of 3a %1 g, 3.25 mmol) dissolved in absolute
THF %5 ml) was added an equimolar amount of silylated
ylide 4 %1.325 g, 3.25 mmol) in THF %5 ml). The reaction
mixture was heated at 558C for 8 h. The reaction was
monitored by TLC. After completion of the reaction, the
4.6.6. 2-ꢀ40-Methoxyphenyl)-4H-1-benzothiopyran-4-one
ꢀ8f). Colorless solid; mp 126±1278C %Lit.12 126±1278C); IR
n
max/cm21 %CHCl3): 1666, 1540, 1243; 1H NMR %CDCl3) d:
3.90 %s, 3H), 6.9±7.03 %m, 5H), 7.5±7.56 %m, 2H), 7.94 %d,

9758
P. Kumar, M. S. Bodas / Tetrahedron 57 ,2001) 9755±9758
1H, Jˆ4 Hz), 8.08 %d, 1H, Jˆ6 Hz). Mass %EI), m/z %%): M1
2. %a) Kumar, P.; Dinesh, C. U.; Pandey, B. Tetrahedron Lett.
1994, 35, 9229. %b) Kumar, P.; Rao, A. T.; Pandey, B. Synth.
Commun. 1994, 24 %22), 3297. %c) Kumar, P.; Saravanan, K.
Tetrahedron 1998, 54, 2161.
268 %80), 240 %40), 225 %22).
4.6.7. 2-ꢀ20-Chlorophenyl)-4H-1-benzothiopyran-4-one
ꢀ8g). Colorless solid; mp 2018C %Lit.18 2048C); IR nmax
/
3. For recent reviews on intramolecular Wittig reactions, see:
%a) Heron, B. M. Heterocycles 1995, 41, 2357. %b) Murphy,
P. J.; Lee, E. S. J. Chem. Soc., Perkin Trans. 1 1999, 3049.
4. Bestmann, H. J.; Bomhard, A.; Dostalek, R.; Pichl, R.;
Riemer, R.; Zimmermann, R. Synthesis 1992, 787.
5. Kumar, P.; Bodas, M. S. Org. Lett. 2000, 2, 3821.
6. %a) Ellis, G. P. Comprehensive Heterocyclic Chemistry;
Katritzky, A. R., Rees, C. W., Eds.; Pergamon: New York,
1984; Vol. 3, Part 2B, pp. 695±718. %b) Hepworth, J. P.
Comprehensive Heterocyclic Chemistry; Katritzky, A. R.,
Rees, C. W., Eds.; Pergamon: New York, 1984; Vol. 3,
pp. 816±830 see also pp 874±883.
1
cm21 %CHCl3): 1694, 1213; H NMR %CDCl3) d: 6.95±
7.00 %m, 1H), 7.44±7.9 %m, 4H), 8.11±8.15 %m, 4H). Mass
%EI), m/z %%): M1 272 %35), 244 %28), 139 %95).
4.6.8. 2-ꢀ20-Nitrophenyl)-4H-1-benzothiopyran-4-one ꢀ8h).
Colorless solid; mp 2848C %Lit.18 2828C); IR nmax/cm21
%CHCl3): 1694, 1540, 1224; H NMR %CDCl3) d: 6.89±
1
7.04 %m, 2H), 7.43±7.57 %m, 4H), 7.91±8.09 %m, 3H).
Mass %EI), m/z %%): M1 283 %80), 139 %76), 123 %38).
4.6.9.
2-ꢀ30-Nitrophenyl)-4H-1-benzothiopyran-4-one
ꢀ8i).19 Colorless solid; mp 215±2168C; IR nmax/cm21
7. %a) Hepworth, J. P. Comprehensive Heterocyclic Chemistry;
Katritzky, A. R., Rees, C. W., Eds.; Pergamon: New York,
1984; Vol. 3, Part 2B, pp. 918±919. %b) Ingall, A. H.
Comprehensive Heterocyclic Chemistry; Katritzky, A. R.,
Rees, C. W., Eds.; Pergamon: New York, 1984; Vol. 3, Part
2B, pp. 941±942.
1
%CHCl3): 1692, 1530, 1243; H NMR %CDCl3) d: 6.9±7.1
%m, 3H), 7.48±8.01 %m, 6H). Mass %EI), m/z %%): M1 283
%80), 139 %95), 123 %25). Anal. Calcd for C15H9NO3S: C,
63.59; H, 3.20; N, 4.94; S, 11.32. Found C, 63.40; H, 3.52;
N, 5.14; S, 11.60.
8. %a) Nakazumi, H.; Ueyama, T.; Kitao, T. J. Heterocycl. Chem.
1984, 21, 193. %b) Wang, H.-K.; Bastow, K. F.; Cosentino,
L. M.; Lee, K-H. J. Med. Chem. 1996, 39, 1975.
%c) Holshouser, M. H.; Loef¯er, L. J.; Hall, I. H. J. Med.
Chem. 1981, 24, 853.
4.6.10. 2-ꢀ30,50-Dimethoxyphenyl)-4H-1-benzothiopyran-
4-one ꢀ8j). Colorless solid; mp 234±2368C %Lit.13 2368C);
IR nmax/cm21 %CHCl3): 1686, 1534, 1215; 1H NMR %CDCl3)
d: 3.9 %s, 6H), 7.25±7.42 %m, 4H), 7.87±8.09 %m, 4H). Mass
%EI), m/z %%): M1 298 %80), 137 %85), 139 %88), 77 %38).
9. %a) Bossert, F. Liebigs Ann. Chem. 1964, 680, 40.
%b) Schneller, S. W. Adv. Heterocycl. Chem. 1975, 18, 60.
%c) Nakazumi, H.; Watanabe, S.; Kitaguchi, T.; Kitao, T.
Bull. Chem. Soc. Jpn 1990, 63, 847.
Acknowledgements
10. %a) Truce, W. E.; Goldhamer, D. L. J. Am. Chem. Soc. 1959,
81, 5795. %b) Yu, X.; Liu, J.; Li, X.; Zhang, G. g.; Fang, L.
Huaxi Yaoxue Zazhi 1997, 12 %4), 230. Chem. Abstr. 1998,
128, 48115. %c) Razdan, R. K.; Bruni, R. J.; Mehta, A. C.;
Weinhardt, K. K.; Papanastassiou, Z. B. J. Med. Chem.
1978, 21 %7), 643. %d) Buggle, K.; Delahunty, J. J.; Philbin,
E. M.; Ryan, N. D. J. Chem. Soc. ,C) 1971, 3168.
One of us %P. K.) is thankful to the Department of Science
and Technology, Government of India for generous funding
of the project %Grant No. SP/S1/G-18/98). We are grateful to
Dr M. K. Gurjar for his support and encouragement. This is
NCL communication No. 6611.
11. Angel, A. J.; Finefrock, A. E.; French, K. L.; Hurst, D. R.;
Williams, A. R.; Rampey, M. E.; Studer-Martinez, S. L.;
Beam, C. F. Can. J. Chem. 1999, 77 %1), 94.
References
1. %a) Krapcho, J.; Turk, C. F.; Piala, J. J. J. Med. Chem. 1968,
11, 361. %b) Philipp, A.; Jirkovsky, I.; Martel, R. R. J. Med.
Chem. 1980, 23, 1372. %c) Nakazumi, H.; Ueyama, T.; Kitao,
T. J. Heterocycl. Chem. 1985, 22, 1593. %d) Malene, C.;
Danree, B.; Laubie, M. Ger. Pat. 2017902, 1970; Chem.
Abstr. 1970, 74, 22698. %e) Malene, C.; Desnoyers, P. Br.
Pat. 1158473, 1969; Chem. Abstr. 1970, 72, 71434.
%f) Watanabe, K.; Saito, T.; Niimura, K. Eur. Pat. Appl. EP
758649, 1997; Chem. Abstr. 1997, 126, 199456.
%g) Tomizawa, K.; Kameo, K.; Saito, H.; Hatayama, K. Jpn.
Kokai Tokkyo Koho JP 02255676, 1990; Chem. Abstr. 1991,
114, 228737. %h) Charris, J.; Dominguez, J.; Lobo, G.;
Riggione, F. Pharm. Pharmacol. Commun. 1999, 5 %2), 107.
%i) Sano, T.; Saijo, K.; Tomizawa, K.; Kameo, K.; Yokomori,
S.; Hatayama, K. Jpn. Kokai Tokkyo Koho JP 04082887,
1992; Chem. Abstr. 1992, 117, 150893. %j) Jeffery, J. A.;
Outt, P. E.; Randall, J. L.; Johnston, J. N.; Murray, P. D.;
O'Brien, L. M.; Weisshaar, P. S.; Ems, B. L. Bioorg. Med.
Chem. Lett. 1996, 6, 995.
12. French, K. L.; Angel, A. J.; Williams, A. R.; Hurst, D. R.;
Beam, C. F. J. Heterocycl. Chem. 1998, 35 %1), 45 and refer-
ences therein.
13. Taylor, A. W.; Dean, D. K. Tetrahedron Lett. 1988, 29, 1845.
14. Wadsworth, D. H.; Detty, M. R. J. Org. Chem. 1980, 45, 4611.
15. Nakazumi, H.; Kitaguchi, T.; Ueyama, T.; Kitao, T. Synthesis
1984, 518.
16. %a) Dike, S. Y.; Ner, D. H.; Kumar, A. Synlett 1991, 13, 443.
%b) Krapcho, J.; Spitzmiller, E. R.; Turk, C. F. J. Med. Chem.
1963, 6, 544. %c) Krapcho, J.; Turk, C. F. J. Med. Chem. 1966,
9, 191. %d) Clarke, P. D.; Fitton, A. O.; Suschitzky, H.;
Wallace, T. W.; Dowlatshahi, H. A.; Suschitzky, J. L.
Tetrahedron Lett. 1986, 27 %1), 91.
17. Nakazumi, H.; Ueyama, T.; Sonoda, H.; Kitao, T. Bull. Chem.
Soc. Jpn 1984, 57, 2323.
18. Levai, A. Heterocycl. Commun. 1999, 5, 419.
19. Dekermendjian, K.; Kahnberg, P.; Witt, M.-R.; Sterner, O.;
Nielsen, M.; Liljefors, T. J. Med. Chem. 1999, 42, 4343.