3-Benzoyl-4-hydroxyisochromen-1-one derivatives, their synthesis and synthetic application

Article abstract of DOI:10.3987/COM-06-10757

3-Benzoyl-1,4-isochromandione derivatives were prepared by cyclization of phenacyl phthalates (2). The cyclization was done in the presence of N-methylpyrrolidone and potassium hydroxide. These compounds served as intermediates for the synthesis of more c

Full text of DOI:10.3987/COM-06-10757

HETEROCYCLES, Vol. 68, No. 9, 2006
1845
HETEROCYCLES, Vol. 68, No. 9, 2006, pp. 1845 - 1859. © The Japan Institute of Heterocyclic Chemistry
Received, 5th April, 2006, Accepted, 29th June, 2006, Published online, 30th June, 2006. COM-06-10757
3-BENZOYL-4-HYDROXYISOCHROMEN-1-ONE DERIVATIVES,
THEIR SYNTHESIS AND SYNTHETIC APPLICATION
Pavel Hradil, a,b,* Radek Melnicky, b Martin Grepl,b,d Kamil Koristek, b Jan
Hlavac, a and Valerio Bertolasi c
a
Department of Organic Chemistry, Palacky University, Tr Svobody 8, 771 46
Olomouc, Czech Republic, hradil@farmak.cz
b Farmak a.s., 771 17 Olomouc, Czech Republic
c Dipartimento di Chimica and Centro di Strutturistica Diffrattometrica, University
of Ferrara, Via L. Borsari, 46, 44100 Ferrara, Italy, m38@unife.it
d Department of Analytical Chemistry, Palacky University, Tr Svobody 8, 771 46
Olomouc, Czech Republic
Abstract – 3-Benzoyl-1,4-isochromandione derivatives were prepared by
cyclization of phenacyl phthalates (2). The cyclization was done in the presence
of N-methylpyrrolidone and potassium hydroxide. These compounds served as
intermediates for the synthesis of more complicated isocoumarine derivatives. A
Wittig reaction with (carbethoxymethylene)triphenyl phosphorane was conducted
in a microwave reactor and resulted in the formation of substituted
4-phenylpyrano[3,2-c]isochromene-2,6-dione.
INTRODUCTION
A number of derivatives of indenoisoquinolines (A) were prepared and subsequently found to be
cytotoxic in human cancer cells (Figure 1).1,2 These compounds were synthesized by reaction of the
corresponding lactone with various primary amines.1,2 For example, the cytostatic compound oracine was
prepared from commercially available benz [d]indeno[1,2-b]pyran-5,11-dione (B) (Figure 1).3

1846
HETEROCYCLES, Vol. 68, No. 9, 2006
O
O
O
O
O
H3CO
H3CO
N
N
O
N
OH
R
H
O
O
O
oracine
B
A
Figure 1
Further, from the literature, it is also known that compounds containing the lactone ring frequently exhibit
a broad spectrum of biological activities – antimicrobial, cytostatic, and so on.4 Their frequent occurrence
in, for example mycotoxins, is also well-documented (Figure 2). Related analogs of these compounds
were developed as potential drugs. Some of them are shown in Fig. 2. For example, the oncologically
active compound NM-3 is in clinical trial, or the compound galloflavin which targets HIV-1 integrase5
could be a useful drug for the treatment of HIV disease. Based on this knowledge we decided to prepare
substituted 1,4-isochromandiones (3) and substituted pyrano[3,2-c]isochromene-2,6-dione (4) (Scheme 1)
as analogs of compound (B) and also galloflavin. This group of compounds is readily available, has not
yet been described and provides many opportunities for structure modification. They may serve as key
intermediates for the synthesis of various biologically active heterocyclic compounds.
O
R1 OH
O
O
CH3
O
O
O
R2
O
O
OH
R3
O
O
OCH3
aflatoxine B1
ochratoxin
patuline
O
O
OH
Me
CO2H
OH
O
O
MeO
HO
HO
.
O
OH O
NM - 3
galloflavin
Figure 2

HETEROCYCLES, Vol. 68, No. 9, 2006
1847
RESULTS AND DISCUSSION
Only few 1,4-isochromandiones substituted by the carbonyl group in the position 3 are known. In general
3-carbethoxy derivatives have been known for some time6~8 though only one compound with substitution
by the carbonyl group in the same position9 has been described. Carbethoxy compounds were prepared by
Claisen condensation from phtalide and diethyloxalate. A compound with the 2-naphthoyl group was
prepared by acid catalyzed cyclization of 2-(3-naphthalen-1-yl-3-oxo-propionyl)benzoic acid ethyl ester
in dichloromethane. For the preparation of the key intermediates, 3-acyl-1,4-isochromandiones, a
synthesis similar to the Gabriel Isoquinoline synthesis was selected. Instead of phenacyl phtalimides,
phenacyl phthalates (2) were chosen. These compounds are simply available by reaction of phthalic acid
monoester salt and phenacyl bromide in acetone and they were subjected to reactions with various
catalysts. Acids were completely inefficient. The use of bases like potassium carbonate, sodium hydride,
and sodium or potassium methoxide, potassium t-butyloxide and so on, was also unsuccessful. The
reaction was successfully performed in dimethyl sulfoxide or amides like dimethylformamide,
dimethylacetamide, 1,3-dimethylimidazolidinone or N-methylpyrrolidone (NMP) by potassium hydroxide
or sodium hydroxide. The reaction takes several hours and the yield was 20 to 80 % depending on
substitution and temperature. The optimal course of reaction was observed in the temperature range from
25 to 45 °C. The course of substitution strongly depended on the substitution of the phenacyl part of the
ester but we did not find a simple dependence between substitution and capability to cyclize.
For example, cyclization of mono chloro derivative (2c) afforded the required product (3c). The reaction
time was longer and the yield was not too high. The cyclization was not observed for dichloro derivatives
(2g) and (2i). On the other hand, derivative (2e) smoothly afforded 3e with very high yield. The progress
of the reaction was checked by TLC. As soon as starting material could no longer be observed, diluted
hydrochloric acid was added to the reaction mixture and the products (3) were isolated as yellow needles.
Compounds (3) were then used as a starting material for the next stage of the synthesis.
In the initial step a Wittig reaction was carried out in toluene or xylene. However, the reaction proceeded
very slowly and even after 20 hours only a small part of the starting material had been consumed resulting
in the compound (4). This being case, we resorted to the use of a microwave reactor. The microwave
reactor is a prototype specially constructed by the Romil company (Brno, Czech Republic). The
maximum power of the microwave source is 250W and microwaves are focused on the reaction area, and
energetic input is regulated. The reaction was done in a melt and only a small amount of N-methyl
pyrrolidone was added. The reaction mixture absorbs microwaves better under these conditions. After
several minutes the reaction was completed. The starting material was not observed by TLC. The required

1848
HETEROCYCLES, Vol. 68, No. 9, 2006
products (4) precipitated after addition of ethyl acetate. Some product remained in the mother liquor due
to its solubility in triphenyl phosphine oxide (Scheme 1). The isolated product was generally very pure.
The structure of the products (4a) and (4b) was confirmed by X-Ray diffraction. (Figure 3 and 4)
In the cyclization of compounds (3e) and (3f), the desired products (4e) and (4f) did not arise and the
reaction mixture contained multifarious unknown compounds.
R3
R2
Br
O
R4
R1
OH
O
R1
R4
O
COO-
R1
R2
R2
R3
NMP
+
O
O
O
KOH
R4
COOC2H5
COOC2H5
R3
1a -j
O
3a-f
2a -j
Ph3P=CHCOOC2H5
O
(CH3CO)2O
O
O
O
O
O
R1
R4
R2
R3
O
O
O
5a
LiOH
CH2(COOC2H5)2
4a-d
O
O
O
COOC2H5
O
O
O
O
H2SO4
O
6a
O
7a
a
b
c
d
e
f
g
h
i
R1 = H, R2 = H,
R1 = H, R2 = H,
R1 = H, R2 = H,
R1 = H, R2 = H,
R1 = H, R2 = Cl,
R3 =H,
R3 = CH3, R4 =H.
R3 = Cl,
R3 = F,
R3 = NH2, R4 =Cl.
R4 = H.
R4 =H.
R4 =H.
R1 = H, R2 = OCH3, R3 = OCH3,R4 =H.
R1 = Cl, R2 = H, R3 = Cl,
R1 = H, R2 = H, R3 = NO2, R4 = H.
R1 = H, R2 = Cl, R3 = H, R4 = Cl.
R1 = H, R2 = NO2, R3 = Cl, R4 = H.
R4 = H.
j
Scheme 1

HETEROCYCLES, Vol. 68, No. 9, 2006
1849
Figure 3. ORTEP view of compound (4a) showing the thermal ellipsoids at 30% level of probability
Figure 4. ORTEP view of compound (4b) showing the thermal ellipsoids at 30% level of probability
After reaction of derivative (3a) with acetic anhydride, acetyl derivative (5a) was prepared. If the same
reaction was done with ethyl 3-chloro-3-oxopropionate and triethylamine in acetone, a different course of
reaction was observed and the compound (6a) was isolated. But yield of the compound (6a) was very low
and did not exceed 15% even if a ten-fold excess of acyl chloride was used. It was noted that the same
compound (6a) is formed by reaction of acetyl derivative (5a) with malonic acid diethyl ester in alkaline
medium. After addition of hydroxide, the slightly yellow reaction mixture turned to an intensively violet
one. Cyclization of the compound (6a) progresses smoothly in sulfuric or polyphosphoric acid and the
compound (7a) is formed.
X-Ray crystal structure determinations.
X-Ray diffraction data for compounds (4a) and (4b) were collected on a Nonius Kappa CCD
diffractometer, at room temperature (T = 295 K), with graphite monochromated Mo Kα radiation (λ =
0.7107 Å) and corrected for Lorentz and polarization effects. The structures were solved by direct
methods (SIR97) 10 and refined (SHELXL-97)11 by full matrix least squares with anisotropic non-H atoms

1850
HETEROCYCLES, Vol. 68, No. 9, 2006
and isotropic hydrogens. All other calculations were accomplished using the system of programs
PARST.12. ORTEP 11 views of compounds (4a) and (4b) are shown in Figures 3 and 4.
Crystal data: 4a, C18H10O4; monoclinic, space group P21/n, a = 12.9485(4), b = 7.5251(2), c = 14.9469(4)
Å, β = 115.578(2)°, V = 1313.68(7) Å3, Z = 4, Dc = 1.468 g cm-3. Intensity data collected with θ ≤ 30°;
3733 independent reflections measured; 2318 reflections observed [I>2σ(I)]. Final R = 0.0469 (observed
reflections), Rw = 0.1376 (all reflections), and S (goodness of fit) = 1.026.
4b, C19H12O4; monoclinic, space group P21/n, a = 7.1121(1), b = 7.7001(1), c = 26.5088(6) Å, β =
96.064(1)°, V = 1443.60(4) Å3, Z = 4, Dc = 1.400 g cm-3. Intensity data collected with θ ≤ 30°; 4134
independent reflections measured; 2571 reflections observed [I>2σ(I)]. Final R = 0.0468 (observed
reflections), Rw = 0.1389 (all reflections), and S (goodness of fit) = 1.053.
EXPERIMENTAL
Melting points were measured in the Kofler apparatus and are uncorrected. TLC was performed on
Polygram Sil G/UV254 with UV light detection and mobile phase n-hexane : ethylacetate 7: 3. Infrared
spectra (KBr discs) were taken with an ATI Unicam Genesis FTIR instrument. MS characterization was
carried out using the DEP-CI-MS-MS (direct exposure probe-chemical ionization-tandem mass
spectrometry) technique with quadrupole ion trap mass analyzer and methane as a CI reagent gas. NMR
spectra were measured with a Bruker Avance 300 spectrometer operating at 300 MHz (1H) and 75 MHz
(13C). The compounds were dissolved in DMSO-d6 and measured at 300 K.
General method of preparation of phthalic acid 1-ethyl ester 2-(2-oxo-2-phenylethyl) ester (2)
Monoethyl ester of phthalic acid (35 g, 0.236 mol) was dissolved in acetone (300 mL) and triethylamine
(23 mL, 0.166 mol) was added. The reaction mixture was stirred and bromoacetophenone derivative
(0.13 mol) was added and the reaction mixture was refluxed with stirring. When substituted
bromoacetophenone was not observed on TLC, solid triethyl ammonium bromide was filtered off and the
filtrate was evaporated to dryness. The oily residue was dissolved in EtOH (70 mL) and the solution was
cooled at 0°C. Crystalline material was filtered off, dried and recrystallized from EtOH.
Phthalic acid 1-ethyl ester 2-(2-oxo-2-phenylethyl) ester (2a)
Yellow solid ( 23.5 g, 58%) mp 75-77 °C; reaction time 3 h.
Anal. Calcd for C18H16O5 (312.32): C, 69.22; H, 5.16. Found: C, 69.21; H, 5.24.
Full MS, m/z (relative intensity) 341 [M+C2H5]+, 313 (<1) [M+H]+, 267 [M+H-C2H5OH]+ 177
,
[C6H4COOC2H5(CO)]+, 163, 149 (100) [C6H4COOH(CO)]+, 133, 121, 119, 105, 91.

HETEROCYCLES, Vol. 68, No. 9, 2006
1851
1H NMR (DMSO-d6, 300 MHz) δ 8.03 (2H, dd, J = 7.5, 1.3 Hz), 7.94-7.88 (1H, m), 7.79-7.69 (4H, m),
7.59 (2H, dd, J = 8.1, 7.4 Hz), 5.75 (2H, s), 4.27 (2H, q, J = 7.1 Hz), 1.27 (3H, t, J = 7.1 Hz); 13C NMR
(DMSO-d6, 75 MHz) δ 192.9, 167.4, 166.6, 134.6, 134.3, 132.7, 132.6, 132.0, 130.9, 129.6, 129.4, 129.2,
128.3, 67.9, 61.9, 14.3.
Phthalic acid 1-ethyl ester 2-(2-oxo-2-p-tolylethyl) ester (2b)
Slight yellow solid (26.7 g, 63 %) mp 86-88 °C; reaction time 2 h.
Anal. Calcd for C19H18O5 (326.34): C, 69.94; H, 5.52. Found: C, 69.82; H, 5.63.
Full MS, m/z (relative intensity) 355 [M+C2H5]+, 327 (<1) [M+H]+, 281 [M+H-C2H5OH]+ 177
,
[C6H4COOC2H5(CO)]+, 149 (100) [C6H4COOH(CO)]+, 133, 119, 105, 91.
1H NMR (DMSO-d6, 300 MHz) δ 7.93 (2H, dd, J = 8.1, 1.4 Hz), 7.91-7.87 (1H, m), 7.80-7.70 (3H, m),
7.40 (2H, d, J = 8.3 Hz), 5.70 (2H, s), 4.27 (2H, q, J = 7.1 Hz), 2.41 (3H, s), 1.27 (3H, t, J = 7.1 Hz); 13C
NMR (DMSO-d6, 75 MHz) δ 192.3, 167.4, 166.6, 145.1, 132.7, 132.5, 132.0, 131.8, 131.0, 129.9, 129.6,
129.1, 128.4, 67.8, 61.9, 21.7, 14.3.
Phthalic acid 1-[2-(4-chloro-phenyl)-2-oxoethyl] ester 2-ethyl ester (2c)
Yellow solid (34.6 g, 77 %) mp 55-57 °C; reaction time 0.5 h.
Anal. Calcd for C18H15O5Cl (346.77): C, 62.35; H, 4.33. Found: C, 61.49; H, 4.27.
Full MS, m/z 375 [M(35Cl)+C2H5]+, 347,349 (<1,<1) [M(35Cl,37Cl)+H]+,
301 [M(35Cl)+H-C2H5OH]+ 177 [C6H4COOC2H5(CO)]+, 153,155 (21,7),
,
149 (100) [C6H4COOH(CO)]+, 141, 139, 127, 125, 121, 105, 91.
1H NMR (DMSO-d6, 300 MHz) δ 8.05 (2H, dd, J = 8.5, 1.7 Hz), 7.93-7.87 (1H, m), 7.79-7.71 (3H, m),
7.67 (2H, dd, J = 8.6, 1.9 Hz), 5.73 (2H, s), 4.27 (2H, q, J = 7.1 Hz), 1.27 (3H, t, J = 7.1 Hz); 13C NMR
(DMSO-d6, 75 MHz) δ 192.1, 167.4, 166.6, 139.4, 132.9, 132.7, 132.6, 132.0, 130.8, 130.3, 129.6, 129.2,
67.9, 61.9, 14.3.
Phthalic acid 1-ethyl ester 2-[2-(4-fluorophenyl)-2-oxoethyl] ester (2d)
Yellow solid (29.2 g, 68 %) mp 59-61 °C; reaction time 0.5 h.
Anal. Calcd for C18H15O5F (330.31): C, 65.45; H, 4.55. Found: C, 65.11; H, 4.53.
Full MS, m/z 359 [M+C2H5]+, 331 (<1) [M+H]+, 311 [M+H-HF]+ 285 [M+H-C2H5OH]+
,
,
177 [C6H4COOC2H5(CO)]+, 149 (100) [C6H4COOH(CO)]+, 137, 123, 109, 91.
1H NMR (DMSO-d6, 300 MHz) δ 8.14 (1H, dd, J = 8.9, 2.1 Hz), 8.11 (1H, dd, J =8.9, 2.1 Hz), 7.93-7.87
(1H, m), 7.79-7.71 (3H, m), 7.43 (2H, ddd, J = 8.9, 8.8, 2.0 Hz), 5.75 (2H, s), 4.27 (2H, q, J = 7.1 Hz),
1.27 (3H, t, J = 7.1 Hz); 13C NMR (DMSO-d6, 75 MHz) δ 167.6, 167.4, 166.6, 132.7, 132.6,
132.0, 131.6, 131.4, 131.1, 131.0, 130.9, 129.6, 129.2, 116.7, 116.4, 67.9, 61.9, 14.3.

1852
HETEROCYCLES, Vol. 68, No. 9, 2006
Phthalic acid 1-[2-(4-amino-3,5-dichlorophenyl)-2-oxoethyl] ester 2-ethyl ester (2e)
Orange solid (26.8 g, 52 %) mp 115-116 °C; reaction time 0.5 h.
Anal. Calcd for C18H15O5NCl2 (396.22): C, 54.56; H, 3.79; N, 3.54. Found: C, 54.73; H, 3.57; N, 3.49.
Full MS, m/z 424 [M(35Cl)+C2H5]+, 396,398,400 (3,2,<1) [M(35Cl,37Cl)+H]+,
350 [M(35Cl)+H-C2H5OH]+ 248, 234, 204, 188, 174, 177 [C6H4COOC2H5(CO)]+, 174,
,
149 (100) [C6H4COOH(CO)]+, 121, 105, 91.
1H NMR (DMSO-d6, 300 MHz) δ 7.90 (2H, s), 7.90-7.85 (1H, m), 7.78-7.70 (3H, m), 6.61 (1H, s), 5.61
(2H, s), 4.27 (2H, q, J = 7.1 Hz), 1.27 (3H, t, J = 7.1 Hz); 13C NMR (DMSO-d6, 75 MHz) δ 167.4, 166.6,
146.6, 132.7, 132.5, 131.9, 131.0, 129.6, 129.1, 128.8, 122.6, 117.9, 117.8, 67.9, 61.9, 14.3.
Phthalic acid 1-[2-(3,4-dimethoxyphenyl)-2-oxoethyl] ester 2-ethyl ester (2f)
Pale yellow solid (36.8 g, 76 %) mp 77-79 °C; reaction time 0.5 h.
Anal. Calcd for C20H20O7 (372.38): C, 64.52; H, 5.38. Found: C, 64.52; H, 5.38.
Full MS, m/z 401 [M+C2H5]+, 373 (2) [M+H]+, 327 [M+H-C2H5OH]+ 179,
,
177 [C6H4COOC2H5(CO)]+, 165, 151, 149 (100) [C6H4COOH(CO)]+, 139, 121, 105, 91.
1H NMR (DMSO-d6, 300 MHz) δ 7.93-7.86 (1H, m), 7.80-7.69 (4H, m), 7.49 (1H, d, J = 1.8 Hz), 7.13
(1H, d, J = 8.5 Hz), 5.70 (2H, s), 4.27 (2H, q, J = 7.1 Hz), 3.88 (3H, s), 3.84 (3H, s), 1.28 (3H, t, J = 7.1
13
Hz); C NMR (DMSO-d6, 75 MHz) δ 191.2, 167.4, 166.7, 154.2, 149.2, 132.6, 132.5, 132.0, 131.1,
129.6, 129.1, 127.1, 123.1, 111.5, 110.5, 67.7, 61.9, 56.3, 56.1, 14.3.
Phthalic acid 1-[2-(2,4-dichlorophenyl)-2-oxoethyl] ester 2-ethyl ester (2g)
Off white solid (33.6 g, 68 %) mp 93-95 °C; reaction time 0.5 h.
Anal. Calcd for C18H14O5Cl2 (381.21): C, 56.66; H, 3.70. Found: C, 57.36; H, 3.72.
Full MS, m/z 409 [M(35Cl)+C2H5]+, 381,383,385 (<1,<1,<1) [M(35Cl,37Cl)+H]+,
335 [M(35Cl) +H-C2H5OH]+ 191, 189, 187, 177 [C6H4COOC2H5(CO)]+, 173, 159,
,
149 (100) [C6H4COOH(CO)]+, 121, 105, 91.
1H NMR (DMSO-d6, 300 MHz) δ 7.91 (1H, d, J = 8.4 Hz), 7.83 (1H, d, J = 2.0 Hz), 7.82-7.78 (1H, m),
7.78-7.70 (3H, m), 7.64 (1H, dd, J = 8.3, 2.1 Hz), 5.54 (2H, s), 4.27 (2H, q, J = 7.1 Hz), 1.27 (3H, t, J =
13
7.1 Hz); C NMR (DMSO-d6, 75 MHz) δ 194.1, 167.3, 166.5, 137.8, 133.8, 132.7, 132.6, 132.5, 132.0,
131.9, 130.9, 130.7, 129.4, 129.2, 128.2, 69.1, 61.9, 14.3.
Phthalic acid 1-ethyl ester 2-[2-(4-nitrophenyl)-2-oxoethyl] ester (2h)
Brown solid (26.0 g, 56 %) mp 55-58 °C; reaction time 1.5 h.
Anal. Calcd for C18H15O7N (357.31): C, 60.50; H, 4.20; N, 3.92. Found: C, 60.11; H, 4.28; N, 4.15.
Full MS, m/z 386 [M+C2H5]+, 358 (<1) [M+H]+, 312 [M+H-C2H5OH]+
,

HETEROCYCLES, Vol. 68, No. 9, 2006
1853
177 [C6H4COOC2H5(CO)]+, 164, 149 (100) [C6H4COOH(CO)]+, 137, 121, 106, 91.
1H NMR (DMSO-d6, 300 MHz) δ 8.40 (2H, ddd, J = 8.8, 2.3, 1.9 Hz), 8.27 (2H, ddd, J = 8.9, 2.1, 1.9
Hz), 7.93-7.86 (1H, m), 7.80-7.71 (3H, m), 5.81 (2H, s), 4.28 (2H, q, J = 7.1 Hz), 1.28 (3H, t, J = 7.1 Hz);
13C NMR (DMSO-d6, 75 MHz) δ 192.4, 167.4, 166.6, 150.9, 138.8, 132.7, 132.6, 132.0, 130.7, 129.9,
129.6, 129.2, 124.5, 68.2, 61.9, 14.3.
Phthalic acid 1-[2-(3,5-dichlorophenyl)-2-oxoethyl] ester 2-ethyl ester (2i)
Pale yellow solid (31.7 g, 64 %) mp 89-91 °C; reaction time 0.5 h.
Anal. Calcd for C18H14O5Cl2 (381.21): C, 56.66; H, 3.70. Found: C, 57.10; H, 3.72.
Full MS, m/z 409 [M(35Cl)+C2H5]+, 381,383,385 (<1,<1,<1) [M(35Cl,37Cl)+H]+,
335 [M(35Cl)+H-C2H5OH]+ 191, 189, 187, 177 [C6H4COOC2H5(CO)]+, 173, 159,
,
149 (100) [C6H4COOH(CO)]+, 121, 105, 91.
1H NMR (DMSO-d6, 300 MHz) δ 7.91 (1H, d, J = 8.4 Hz), 7.83 (1H, d, J = 2.3 Hz), 7.82-7.78 (1H, m),
7.78-7.70 (3H, m), 7.64 (1H, dd, J = 8.9, 1.7 Hz), 5.54 (2H, s), 4.27 (2H, q, J = 7.1 Hz), 1.27 (3H, t, J =
13
7.1 Hz); C NMR (DMSO-d6, 75 MHz) δ 194.1, 167.3, 166.5, 137.8, 133.8, 132.7, 132.6, 132.5, 132.0,
131.9, 130.9, 130.6, 129.4, 129.2, 128.2, 69.1, 61.9, 14.3.
Phthalic acid 1-[2-(4-chloro-3-nitrophenyl)-2-oxoethyl] ester 2-ethyl ester (2j)
Yellow solid (31.6 g, 62 %) mp 73-75 °C; reaction time 0.5 h.
Anal. Calcd for C18H14O7NCl (391.77): C, 55.18; H, 3.58; N, 3.58. Found: C, 55.13; H, 3.54; N, 3.60.
Full MS, m/z 420 [M(35Cl)+C2H5]+, 392,394 (<1,<1) [M(35Cl,37Cl)+H]+,
346 [M(35Cl)+H-C2H5OH]+ 200, 198, 183, 177 [C6H4COOC2H5(CO)]+, 170, 163,
,
149 (100) [C6H4COOH(CO)]+, 121, 105, 91.
1H NMR (DMSO-d6, 300 MHz) δ 8.66 (1H, d, J = 1.9 Hz), 8.29 (1H, dd, J = 8.5, 2.0 Hz), 8.02 (1H, d, J
= 8.4 Hz), 7.92-7.85 (1H, m), 7.80-7.72 (3H, m), 5.79 (2H, s), 4.27 (2H, q, J = 7.1 Hz), 1.28 (3H, t, J =
13
7.1 Hz); C NMR (DMSO-d6, 75 MHz) δ 191.1, 167.3, 166.6, 148.4, 133.9, 133.1, 132.9, 132.6, 132.0,
130.7, 130.6, 129.5, 129.2, 125.4, 68.0, 61.9, 14.3.
General Method of the preparation of 3-Acyl-4-hydroxy-isochromen-1-ones (3)
Phenacyl phthalates (2) (25 mmol) were dissolved in NMP (30 mL) and KOH (2.8 g; 50 mmol) was
added. The reaction mixture was stirred for 3.5 h at temperature 25 to 50 °C. Then the reaction
mixture was poured into water (70 mL). The solution was acidified with hydrochloric acid to pH 5 and
the solid product was filtered off after 6 h of stirring. The isolated product was crystallized from
EtOH. Yield, reaction time and melting points are summarized as follows:

1854
HETEROCYCLES, Vol. 68, No. 9, 2006
3-Benzoyl-4-hydroxyisochromen-1-one (3a)
Yellow solid (4.8 g, 72 %) mp 168-172 °C; reaction time 3.5 h; reaction temperature 25°C.
Anal. Calcd for C16H10O4 (266.25): C, 72.18; H, 3.79. Found: C, 71.78; H, 4.07.
Full MS, m/z (relative intensity) 295 [M+C2H5]+, 267 (40) [M+H]+, 189 [M+H-C6H6]+
,
161 [M+H-C6H5COH]+, 133 [C6H4CO(CO)]+, 105 (100) [C6H5CO]+, 91; MS2(267,w5,EV1.5), m/z 237,
221, 209, 189, 181, 161, 152, 133, 105.
1H NMR (DMSO-d6, 300 MHz) δ 8.28 (1H, ddd, J = 7.9, 1.9, 0.7 Hz), 8.17 (1H, ddd, J = 7.9, 1.9, 0.7 Hz),
8.11-8.04 (4H, m), 7.93 (1H, ddd, J = 7.7, 7.5, 1.5 Hz), 7.71 (1H, ddd, J = 7.5, 7.3, 2.4 Hz), 7.61 (1H, ddd,
13
J = 7.6, 7.2, 1.5 Hz); C NMR (DMSO-d6, 75 MHz) δ 189.9, 158.4, 135.9, 135.2, 133.7, 133.6, 133.0,
131.8, 130.0, 128.9, 124.5, 124.3.
4-Hydroxy-3-(4-methylbenzoyl)isochromen-1-one (3b)
Yellow solid (3.7 g, 53 %) mp 148-150 °C; reaction time 2.5 h; reaction temperature 25°C.
Anal. Calcd for C17H12O4 (280.27): C, 72.86; H, 4.29. Found: C, 72.58; H, 4.38.
Full MS, m/z 309 [M+C2H5]+, 281 (50) [M+H]+, 189 [M+H-C6H5CH3]+
,
161 [M+H-C6H4CH3(COH)]+, 133 [C6H4CO(CO)]+, 119 (100) [C6H4CH3(CO)]+, 105 [C6H5CO]+, 91;
MS2(281,w5,EV1.5), m/z 265, 251, 235, 223, 195, 189, 161, 133, 119, 105.
1H NMR (DMSO-d6, 300 MHz) δ 8.27 (1H, ddd, J = 7.9, 1.9, 0.7 Hz), 8.16 (1H, ddd, J = 7.9, 1.1, 0.6 Hz),
8.07 (1H, ddd, J = 7.9, 7.3, 1.1 Hz), 8.01 (2H, dd, J = 8.4, 1.1 Hz), 7.92 (1H, ddd, J = 7.8, 7.4, 1.2 Hz),
7.42 (2H, d, J = 8.3 Hz ), 2.43 (3H, s); 13C NMR (DMSO-d6, 75 MHz) δ 188.6, 158.4, 144.4, 135.9, 133.5,
133.1, 132.8, 131.8, 130.2, 130.0, 129.5, 124.4, 124.2, 21.7.
3-(4-Chlorobenzoyl)-4-hydroxyisochromen-1-one (3c)
Yellow solid (3.9 g, 52 %) mp 177-178 °C; reaction time 100 min; reaction temperature 45°C.
Anal. Calcd for C16H9O4Cl (300.7): C, 63.91; H, 3.02. Found: C, 63.51; H, 2.93.
Full MS, m/z 329,331 [M(35Cl,37Cl)+C2H5]+, 301,303 (54,18) [M(35Cl,37Cl)+H]+,
265 [M+H-HCl]+ 189 [M+H-C6H5Cl]+ 161 [M+H-C6H4Cl(COH)]+,
,
,
139,141 (100,33) [C6H4Cl(CO)]+,133 [C6H4CO(CO)]+, 119, 105 [C6H5CO]+, 91; MS2(302,w5,EV1.5),
m/z 189, 161, 141, 139.
1H NMR (DMSO-d6, 300 MHz) δ 8.29 (1H, ddd, J = 7.9, 1.0, 0.7 Hz), 8.17 (1H, ddd, J = 7.9, 1.1, 0.7 Hz),
8.09 (2H, dd, J = 8.4, 1.5 Hz), 8.08 (1H, ddd, J = 7.6, 7.5, 0.8 Hz), 7.94 (1H, ddd, J = 7.6, 7.4, 0.8 Hz),
7.70 (2H, dd, J = 8.5, 1.6 Hz); 13C NMR (DMSO-d6, 75 MHz) δ 158.4, 138.6, 135.9, 134.2,
133.7, 133.0, 131.9, 131.7, 130.0, 129.1, 124.5, 124.3.
3-(4-Fluorobenzoyl)-4-hydroxyisochromen-1-one (3d)

HETEROCYCLES, Vol. 68, No. 9, 2006
1855
Yellow solid (3.6 g, 50 %) mp 195-198 °C; reaction time 1.5 h; reaction temperature 25°C.
Anal. Calcd for C16H9O4F (284.24): C, 67.61; H, 3.17. Found: C, 67.25; H, 3.09.
Full MS, m/z 313 [M+C2H5]+, 285 (50) [M+H]+, 265 [M+H-HF]+ 189 [M+H-C6H5F]+
,
,
161 [M+H-C6H4F(COH)]+, 133 [C6H4CO(CO)]+, 123 (100) [C6H4F(CO)]+, 119, 109,
105 [C6H5CO]+, 91; MS2(285,w5,EV1.5), m/z 123.
1H NMR (DMSO-d6, 300 MHz) δ 8.29 (1H, ddd, J = 7.8, 1.2, 0.7 Hz), 8.21-8.14 (3H, m), 8.08 (1H, ddd,
J = 7.6, 7.5, 0.8 Hz), 7.93 (1H, ddd, J = 7.6, 7.5, 0.7 Hz), 7.48 (1H, dd, J = 9.0, 2.0 Hz), 7.45 (1H, dd, J =
13
8.9, 1.9 Hz); C NMR (DMSO-d6, 75 MHz) δ 187.6, 167.1, 163.7, 158.4, 135.9, 133.6, 133.2, 133.1,
133.0, 132.1, 131.8, 130.0, 124.4, 124.3, 116.3, 116.0.
3-(4-Amino-3,5-dichlorobenzoyl)-4-hydroxyisochromen-1-one (3e)
Orange solid (7.2 g, 82 %) mp 244-248 °C; reaction time 2 h; reaction temperature 45°C.
Anal. Calcd for C16H9O4NCl2 (350.15): C, 54.87; H, 2.57; N, 4.00. Found: C, 54.82; H, 2.27; N, 3.66.
Full MS, m/z 378,380,382 [M(35Cl,37Cl)+C2H5]+, 350,352,354 (90,60,10) [M(35Cl,37Cl)+H]+, 188,190,192
(100,65,11) [C6H2NH2(Cl)(Cl)(CO)]+, 149, 133 [C6H4CO(CO)]+, 123, 119,
105 [C6H5CO]+, 91; MS2(352,w5,EV1.5), m/z 192, 190, 188, 165, 163, 161, 133.
1H NMR (DMSO-d6, 300 MHz) δ 8.26 (1H, ddd, J = 7.9, 0.8, 0.6 Hz), 8.16-8.09 (3H, m), 8.04 (1H, ddd,
J = 7.7, 7.3, 1.5 Hz), 7.90 (1H, ddd, J = 7.7, 7.4, 1.5 Hz), 6.75 (1H, bs); 13C NMR (DMSO-d6, 75 MHz) δ
158.4, 146.6, 135.9, 133.4, 133.1, 131.9, 130.9, 129.9, 124.1, 117.6 .
3-(3,4-Dimethoxybenzoyl)-4-hydroxyisochromen-1-one (3f)
Yellow solid (1.7 g, 21 %) mp 180-220 °C; reaction time 4 h; reaction temperature 25°C.
Anal. Calcd for C18H14O6 (326.31): C, 66.26; H, 4.29. Found: C, 66.09; H, 4.18.
Full MS, m/z 355 [M+C2H5]+, 327 (100) [M+H]+, 189 [M+H-C6H4(CH3O)2]+
,
165 [C6H3(CH3O)2(CO)]+, 161 [M+H-C6H3(CH3O)2(COH)]+, 138, 133 [C6H4CO(CO)]+,
105 [C6H5CO]+, 91; MS2(327,w5,EV1.5), m/z 189, 165, 161, 138, 133, 123.
1H NMR (DMSO-d6, 300 MHz) δ 8.30 (1H, dd, J = 7.8, 1.3 Hz), 8.18 (1H, dd, J = 7.7, 1.2 Hz), 8.08 (1H,
ddd, J = 7.7, 7.5, 1.5 Hz), 7.99-7.90 (2H, m), 7.93 (2H, dd, J = 7.4, 7.3 Hz), 3.91 (3H, s), 3.85 (3H, s);
13C NMR (DMSO-d6, 75 MHz) δ 158.4, 138.6, 135.9, 134.2, 133.7, 133.0, 131.9, 131.7, 130.0, 129.1,
124.5.
General procedure for preparation of 4-substituted-pyrano[3,2-c]isochromene-2,6-diones (4)
The mixture of 3-acyl-4-hydroxyisochromen-1-one (3) (2 mmol), (carbethoxymethylene)triphenyl
phosphorane (0.85 g, 2.44 mmol) and NMP (0.1 g) was heated in a microwave reactor. Until the
reaction mixture had melted (ca. 40 to 60 sec), the reactor was heated with 70% of the microwave energy,

1856
HETEROCYCLES, Vol. 68, No. 9, 2006
thereafter the energy was reduced to 33%. The total reaction time was 7 minutes at a reaction temperature
of approx. 90 °C. The starting material was not observed in the reaction mixture by TLC. Then 10 mL of
ethyl acetate was added and the reaction mixture was cooled to 0 °C for 1 h. Precipitated solid was
filtered off and washed with EtOAc, water and dried. Yield and results are summarized as follows:
4-Phenylpyrano[3,2-c]isochromene-2,6-dione (4a)
Beige solid (0.41 g, 70 %) mp 219-225 °C; reaction time 7 min.
Anal. Calcd for C18H10O4 (290.27): C, 74.48; H, 3.47. Found: C, 74.40; H, 3.53.
Full MS, m/z (relative intensity) 331 [M+C3H5]+, 319 [M+C2H5]+, 291 (100) [M+H]+,
263 [M+H-CO]+ 235 [M+H-CO-CO]+, 219, 206, 191; MS2(291,w5,EV1.5), m/z 263, 262, 245, 235, 234,
,
219, 218, 207, 191, 189, 179, 178.
1H NMR (DMSO-d6, 300 MHz) δ 8.27 (1H, ddd, J = 8.1, 0.7, 0.6 Hz), 8.12-8.05 (2H, m), 7.90-7.81 (1H,
13
m), 7.80-7.72 (2H, m), 7.62-7.55 (3H, m), 6.66 (1H, s); C NMR (DMSO-d6, 75 MHz) δ 159.0, 158.9,
149.6, 139.6, 136.4, 135.1, 132.0, 131.8, 131.0, 130.3, 129.9, 129.5, 129.1, 122.0, 121.7, 115.0.
4-p-Tolylpyrano[3,2-c]isochromene-2,6-dione (4b)
Beige solid (0.21 g, 34 %) mp 237-240 °C; reaction time 7 min.
Anal. Calcd for C19H12O4 (304.03): C, 75.06; H, 3.98. Found: C, 75.30; H, 3.99.
Full MS, m/z 345 [M+C3H5]+, 333 [M+C2H5]+, 305 (100) [M+H]+, 277 [M+H-CO]+
,
249 [M+H-CO-CO]+, 233, 220, 205, 191; MS2(305,w5,EV1.5), m/z 277, 276, 259, 249, 248, 233, 231,
221, 220, 218, 205, 203, 202, 193, 178.
1H NMR (DMSO-d6, 300 MHz) δ 8.27 (1H, ddd, J = 8.1, 0.7, 0.6 Hz), 8.11-8.05 (2H, m), 7.89-7.81 (1H,
13
m), 7.67 (2H, dd, J = 8.2, 1.6 Hz), 7.40 (2H, d, J = 8.3 Hz), 6.62 (1H, s), 2.42 (3H, s); C NMR
(DMSO-d6, 75 MHz) δ 159.0, 149.5, 141.1, 139.5, 136.3, 135.2, 131.8, 130.3, 129.9, 129.7, 129.5, 129.1,
122.0, 121.7, 114.4, 21.4.
4-(4-Chlorophenyl)pyrano[3,2-c]isochromene-2,6-dione (4c)
Off white solid (0.32 g, 50 %) mp 314-320 °C; reaction time 15 min.
Anal. Calcd for C18H9O4Cl (324.71): C, 66.58; H, 2.79. Found: C, 65.90; H, 2.90.
Full MS, m/z 365,367 [M(35Cl,37Cl)+C3H5]+, 353,355 [M(35Cl,37Cl)+C2H5]+, 325,327 (100,33)
[M(35Cl,37Cl)+H]+, 297,299 [M(35Cl,37Cl)+H-CO]+ 269,271 [M(35Cl,37Cl)+H-CO-CO]+, 247, 233, 218,
,
205; MS2(326,w5,EV1.5), m/z 299, 298, 297, 296, 271, 269, 253, 251, 243, 241, 234, 233, 218, 206, 205,
189, 178, 176.
1H NMR (DMSO-d6, 300 MHz) δ 8.28 (1H, ddd, J = 8.1, 0.7, 0.6 Hz), 8.12-8.04 (2H, m), 7.89-7.82 (1H,
13
m), 7.79 (2H, ddd, J = 8.5, 2.4, 1.9 Hz), 7.67 (2H, ddd, J = 8.6, 2.2, 2.0 Hz), 6.70 (1H, s); C NMR

HETEROCYCLES, Vol. 68, No. 9, 2006
1857
(DMSO-d6, 75 MHz) δ 158.9, 158.8, 148.4, 139.6, 136.4, 136.0, 134.9, 131.9, 131.4, 130.8, 130.3, 129.8,
129.2, 122.0, 121.8, 115.2.
4-(4-Fluorophenyl)pyrano[3,2-c]isochromene-2,6-dione (4d)
Beige solid (0.27 g, 44 %) mp 289-292 °C; reaction time 10 min.
Anal. Calcd for C18H9O4F (308.26): C, 70.13; H, 2.94. Found: C, 70.20; H, 3.10.
Full MS, m/z 349 [M+C3H5]+, 337 [M+C2H5]+, 309 (100) [M+H]+, 289 [M+H-HF]+ 281 [M+H-CO]+
,
,
253 [M+H-CO-CO]+, 238, 224; MS2(309,w5,EV1.5), m/z 281, 280, 263, 253, 252, 237, 235, 225, 224,
209, 207, 205, 197, 196, 177, 176.
1H NMR (DMSO-d6, 300 MHz) δ 8.28 (1H, d, J = 8.1 Hz), 8.12-8.04 (2H, m), 7.90-7.81 (3H, m), 7.45
(2H, ddd, J = 9.0, 8.9, 1.9 Hz), 6.68 (1H, s); 13C NMR (DMSO-d6, 75 MHz) δ 158.4, 147.9, 139.0, 135.8,
131.6, 131.5, 131.3, 129.8, 129.3, 127.8, 121.4, 121.2, 115.8, 115.5, 114.5 .
Acetic acid 3-benzoyl-1-oxo-1H-isochromen-4-yl ester (5a)
Compound (3a) (2 g , 7.51 mmol) and acetic anhydride were mixed and p-toluenesulfonic acid (0.1 g) was
added. The reaction mixture was refluxed for 3 h (compound (3a) was not observed on TLC). Acetic acid
and acetic anhydride were evaporated in vacuo and the residue was crystallized from AcOEt. Yield was
2.3 g (99.3 % theory), mp 140-143.5 °C.
Anal. Calcd for C18H12O5 (308.28): C, 70.13; H, 3.92. Found: C, 70.35; H, 3.89.
full MS, m/z (relative intensity) 349 [M+C3H5]+, 337 [M+C2H5]+, 309 (6) [M+H]+, 295, 267 (100)
[M+H-COCH3+H]+ 231, 189, 133, 105, 91; MS2(309,w5,EV1.5), m/z 293, 280, 267, 265, 262, 218, 189,
,
145, 133, 105.
1H NMR (DMSO-d6, 300 MHz) δ 8.30 (1H, dd, J = 7.9, 0.8 Hz), 8.04 (1H, ddd, J = 7.2, 6.8, 1.3 Hz),
7.97-7.82 (4H, m), 7.73 (1H, ddd, J = 7.5, 7.4, 1.4 Hz), 7.68 (2H, ddd, J = 7.8, 7.4, 1.4 Hz), 2.19 (3H, s);
13C NMR (DMSO-d6, 75 MHz) δ 186.00, 168.32, 158.60, 140.94, 135.59, 133.95, 133.70, 132.31,
131.49, 129.50, 129.45, 128.53, 123.09, 121.92, 19.92 .
2,6-Dioxo-4-phenyl-2,6-dihydropyrano[3,2-c]isochromene-3-carboxylic acid ethyl ester (6a)
Diethylmalonate (520 mg, 3.24 mmol) was dissolved in THF (3 mL) and a very fine powder of
LiOH·H2O (68 mg, 1.62 mmol) was added. A solution of acetyl derivative (5) (100 mg, 0.32 mmol) in
THF (4 mL) was added to this suspension at temperature 20 – 25 °C. After 90 min no acetyl derivative
(5) was observed on the TLC (n-hexane : AcOEt 7 : 5). The solvent was evaporated in vacuo, water was
added and the water suspension extracted by AcOEt (2 x 25 ml). After drying by sodium sulfate and
filtration the organic layer was evaporated to dryness: The residue was dissolved in MeOH and
cyclohexane was added. The precipitate was filtered off and yielding 65 mg (55%), mp 170-172 °C.

1858
HETEROCYCLES, Vol. 68, No. 9, 2006
Anal. Calcd for C21H14O6 (362.33): C, 69.61; H, 3.92. Found: C, 69.60; H, 3.95.
full MS, m/z 403 [M+C3H5]+, 391 [M+C2H5]+, 363 (45) [M+H]+, 334 [M+H-C2H5]+ 317 (100)
,
[M+H-C2H5OH]+ 306, 289, 261, 233; MS2(363,w5,EV1), m/z 334, 317, 306, 289, 261, 233, 221, 205,
,
193.
1H NMR (DMSO-d6, 300 MHz) δ 8.27 (1H, ddd, J = 7.8, 0.9, 0.8 Hz), 8.14-8.05 (2H, m), 7.88 (1H, ddd,
J = 6.7, 6.4, 2.2 Hz), 7.61-7.55 (3H, m), 7.52-7.47 (2H, m), 4.05 (2H, q, J = 7.0 Hz), 0.91 (3H, t, J = 7.0
13
Hz); C NMR (DMSO-d6, 75 MHz) δ 162.73, 158.37, 155.97, 147.68, 139.84, 135.93, 134.03, 131.92,
130.24, 129.84, 129.71, 128.75, 128.43, 128.39, 121.77, 121.53, 119.82, 61.54, 13.26.
5,12-Dioxaindeno[1,2-a]phenanthrene-6,7,13-trione (7a)
Ethyl ester (6a) (1.07 g, 2.95 mmol) was dissolved in sulfuric acid (5 mL) and the reaction mixture was
heated to 130-140 °C for 75 min. At this stage the starting material was no longer observed in TLC. The
reaction mixture was cooled to lab temperature and EtOH (30 mL) was added. The reaction mixture was
stirred for 5 min and then diluted with water (20 mL). The red precipitate was filtered off, washed with a
mixture of ethanol (1.5 mL) and water (1.5 mL) and then with ethanol (2 mL). The isolated compound (7)
was crystallized from DMF. 0.66 g (71 %) of red needles were isolated, mp 318-326 °C.
Anal. Calcd for C19H8O5 (316.26): C, 72.16; H, 2.55. Found: C, 72.00; H, 2.62.
full MS, m/z 357 [M+C3H5]+, 345 [M+C2H5]+, 317 (100) [M+H]+, 289 [M+H-CO]+ 261 [M+H-CO-CO]+,
,
233 [M+H-CO-CO-CO]+, 133, 105, 91; MS2(317,w5,EV1), m/z 289, 261, 245, 233, 217, 205, 189.
1H NMR (DMSO-d6, 300 MHz) δ 8.38 (1H, ddd, J = 7.6, 1.1, 0.6 Hz), 8.23-8.10 (3H, m), 7.99 (1H, ddd,
13
J = 7.4, 7.2, 1.5 Hz), 7.87-7.79 (1H, m), 7.76-7.71 (2H, m); C NMR (DMSO-d6, 75 MHz) δ 157.93,
154.84, 153.23, 152.77, 147.50, 136.11, 135.27, 134.95, 133.91, 133.52, 132.48, 130.28, 126.36, 123.83,
123.08, 122.77.
Supplementary material
Complete crystallographic data (excluding structural factors) for the structures in this paper have been
deposited with the Cambridge Crystallographic Data Centre and allocated the deposition numbers CCDC
276393 - 276394. Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union
Road, Cambridge CB2 1EZ, UK [fax: +44(0)-1223-336033; e-mail: deposit@ccdc.cam.ac.uk, or
http://www.ccdc.cam.ac.uk/conts/retrieving.html
ACKNOWLEDGEMENT
We are grateful to the Ministry of Education, Youth and Sport of the Czech Republic, for the grant
MSM6198959216.

HETEROCYCLES, Vol. 68, No. 9, 2006
1859
REFERENCES
1. M. Cushman, M. Jayaraman, J. A. Vroman, A. K. Fukunaga, B. M. Fox, G. Kohlhagen, D.
Strumberg, and Y. Pommier, J. Med. Chem., 2000, 43, 3688.
2. M. Nagarajan, A. Morrell, B. C. Fort, M. R. Meckley, S. Antony, G. Kohlhagen, Y. Pommier, and M.
Cushman, J. Med. Chem., 2004, 47, 5651.
3. J. Michalsky, (VUFB a.s., Praha) United States Patent 5,597,831, 1997.
4. V. Betina, ´Mykotoxíny, ´Alfa, Bratislava, 1990.
5. H. Hong, N. Neamati, H. E. Winslow, J. L. Christensen, A. Orr, Y. Pommier, and G. W. A. Milne,
Antivir. Chem. Chemother., 1998, 9, 461.
6. D. Molho and J. Aknin, Bull. Soc. Chim. Fr., 1967, 2224.
7. C. Bhakta, Indian. J. Chem., Sect. B: Org. Chem. Incl. Med. Chem., 1986, 25B, 189.
8. N. S. Narasimhan and S. S. Kusurkar, Indian. J. Chem., Sect. B: Org. Chem. Incl. Med. Chem. 1983,
22B, 349.
9. R. M. Moriarty, R. K. Vaid, T. E. Hopkins, B. K. Vaid, and O. Prakash, Tetrahedron Lett., 1990, 31,
201.
10. A. Altomare, M. C. Burla, M. Camalli, G. L. Cascarano, C. Giacovazzo, A. Guagliardi, A. G. G.
Moliterni, G. Polidori, and R. Spagna, J. Appl. Crystallogr., 1999, 32, 115.
11. G. M Sheldrick, ´SHELXL-97, Program for Crystal Structures Refinement. ´University of Göttingen,
Germany, 1997.
12. M. Nardelli, J. Appl. Crystallogr., 1995, 28, 659.