A convenient and highly regio and stereoselective method for the synthesis of (E)-3-alkylidene isobenzofuran-1(3H)-ones (phthalides)

Article abstract of DOI:10.1016/S0040-4020(01)00943-7

2-Iodobenzyl alcohol on treatment with acetylenic carbinols in the presence of a palladium catalyst and copper(I) iodide as a co-catalyst afforded disubstituted alkynes. Jones oxidation of the disubstituted alkynes led to (E)-3-alkylidene isobenzofuran-1(

Full text of DOI:10.1016/S0040-4020(01)00943-7

TETRAHEDRON
Pergamon
Tetrahedron 57 *2001) 9475±9480
A convenient and highly regio and stereoselective method for the
synthesis of ꢀE)-3-alkylidene isobenzofuran-1ꢀ3H)-ones
ꢀphthalides)
Rupa Mukhopadhyay and Nitya G. Kundup
Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Calcutta 700 032, India
Received 5 June 2001; revised 29 August 2001; accepted 20 September 2001
AbstractÐ2-Iodobenzyl alcohol on treatment with acetylenic carbinols in the presence of a palladium catalyst and copper*I) iodide as a co-
catalyst afforded disubstituted alkynes. Jones oxidation of the disubstituted alkynes led to *E)-3-alkylidene isobenzofuran-1*3H)-ones in
good yields in a highly regio and stereoselective manner. The E-isomers were obtained exclusively instead of the more stable Z-isomers.
q 2001 Elsevier Science Ltd. All rights reserved.
Isobenzofuran *IBF)
1 and Isobenzofuran-1*3H)-one
*phthalide) 2 are integral parts of many naturally occurring
substances.1±6 For example, the papulacandins 3 are a group
of antifungal agents from Papularia Spherosperma which
exhibit potent in vitro activity against Candida albicans
and related microorganisms.7±9 Recently, the common
opportunistic infection in AIDSpatients, pneumocystis
carvini pneumonia has been effectively overcome by new
members of the papulacandin family, e.g. 3d *Mer-WF
3010) and 3e *L-687-781).10 Similarly, isobenzofuran-
1*3H) ones *phthalides) possess a wide range of medicinal
properties.11
In view of their importance, various methods have been
developed previously for the synthesis of isobenzofuran-
1*3H)-ones *phthalides).12 However, only a few palladium
mediated syntheses of isobenzofuran-1*3H)ones *phtha-
lides) were reported.13 In recent years, we have developed
methods for the synthesis of various benzofused hetero-
cyclic compounds e.g. benzofurans,14 phthalides,13 quino-
lines and quinolones,15 1,4-benzodioxanes,16 3,4-dihydro-
2H-1,4-benzoxazines,17 isoindolinones,18 ¯avones and
¯avanones,19 benzodioxepinones and benzoxazepinones,20
and benzothiazolines21 by palladium catalysed reactions
with terminal alkynes.22 Because of the biological impor-
tance of the isobenzofuran-1-*3H)ones and the lack of many
convenient palladium catalysed procedures for their syn-
thesis, we were prompted to develop a general and ef®cient
method for the synthesis of isobenzofuran-1-*3H)-ones
starting from 2-iodobenzyl alcohol and acetylenic carbinols.
With that purpose, we reacted 2-iodobenzyl alcohol 4 with
Keywords: alkynes; isobenzofuran-1*3H)ones; palladium catalysis.
Corresponding author. Tel.: 191-33-473-4971; fax: 191-33-473-2805;
e-mail: ocrm@mahendra.iacs.res.in
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020*01)00943-7

9476
R. Mukhopadhyay, N. G. Kundu / Tetrahedron 57 .2001) 9475±9480
Scheme 2.
Scheme 1.
obtained. Similarly, the use of Pd*OAc)2 *5 mol%),
K2CO3 *5 equiv.) and Bu4NBr *0.5 equiv.) in DMF at rt
for 24 h. did not give any products.
acetylenic carbinols 5±14 with a terminal alkyne function-
ality in the presence of a palladium catalyst and cuprous
iodide as a co-catalyst.22c,f The reactions were usually
carried out by stirring a mixture of 2-iodobenzyl alcohol
4 *1 mmol) and acetylenic carbinols 5±14 *1.5 mmol) in
DMF and Et3N in the presence of bis*triphenylphosphine)-
palladium*II)chloride *5 mol%), copper*I)iodide *8 mol%)
at room temparature for 24 h. It was observed that the
disubstituted alkynes *15±24) were the major products23b
*Scheme 1 and Table 1).
Interestingly it was observed that the compounds 15±24
were smoothly oxidised using Jones oxidation to yield the
3-alkylidene isobenzofuran-1*3H)ones *phthalides) 25±34
in excellent yields. The structures of compounds 25±34 as
phthalides follow from their analytical and spectroscopic
data. In IR, the presence of absorption at 1799±1786 cm21
indicated the g-lactone ring, whereas a vinylic hydrogen
1
could be seen at d 7.21±6.94 in the H NMR spectra. The
isobenzofuran-1*3H)ones were given the E-stereochemistry
on the basis of the presence of a down®eld proton at d 9.03±
8.96, which was assigned to the C-4 aromatic hydrogen
which was shifted down®eld due to the proximity of
the aroyl group. For the corresponding isobenzofuran-
1*3H)ones *phthalides) of Z-stereochemistry, the aromatic
signals were seen between d 7.3±8.2.24±26 Also, for
Z-isobenzofuranones *phthalides) 35±38 the vinylic hydro-
gen was at higher ®eld *d 6.70±6.78) compared to the
vinylic hydrogens of E-isobenzofuranones 25±34 which
were at d 7.21±6.94 due to the deshielding effect of the
ring oxygen. The E-con®guration of compounds 25±34
also follows from their conversion to the corresponding
isobenzofuranones of Z-con®guration by treatment with
The structures of the acyclic products *disubstituted
alkynes) 15±24 follow from their analytical and spectro-
1
scopic data. In the H NMR, the benzylic ±CH2± group
could be seen at d 4.7±4.8 and the CHOH at d 5.55±5.87
as singlets. In the 13C NMR, peaks at d 94 and 84 *CuC),
65.3 *CHOH) and 63.9 *CH2) were con®rmative of the
structures of the disubstituted alkynes. We have also used
other palladium-catalysed conditions for the reactions of
2-iodobenzyl alcohol with acetylenic carbinols but have
obtained the disubstituted alkynes in poor yields only or
not at all. For example, with PdCl2*PPh3)2 *3.5 mol%),
CuI *8 mol%), Et3N *4 equiv.), DMF at 808C for 24 h,
only 15±20% of the disubstituted alkynes could be
Table 1. Palladium-catalysed reactions of 2-iodobenzyl alcohol 4 with acetylenic carbinols 5±14 and subsequent Jones oxidation of the products 15±24 to 3-
alkylidene isobenzofuran-1*3H)ones *phthalides) 25±34
Entry
Acetylenic carbinols
*5±14)
Disubstituted alkynesa *%)
*15±24)
Isobenzofuran-1*3H)-onesb *%)
*25±34)
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
5, C6H5
6, C6H4Me-o
7, C6H4Me-m
8, C6H4Me-p
9, C6H4OMe-o
10, C6H4OMe-m
11, C6H4OMe-p
12, C6H4F-p
13, C6H4Cl-p
14, 3,4-methylene dioxy-phenyl
15, *60)
16, *73)
17, *60)
18, *56)
19, *58)
20, *69)
21, *56)
22, *50)
23, *56)
24, *75)
25, *49)
26, *45)
27, *40)
28, *51)
29, *52)
30, *50)
31, *50)
32, *52)
33, *48)
34, *40)
a
Yields are based on 2-iodobenzylalcohol.
Yields are based on the corresponding disubstituted alkynes.
b

R. Mukhopadhyay, N. G. Kundu / Tetrahedron 57 .2001) 9475±9480
9477
sulphuric acid *see Scheme 2 and Section 1). Though the
Z-isomer is more stable than the corresponding E-isomer,
we got exclusively the isobenzofuran-1-ones 25±34 of
E-con®guration from the Jones oxidation of the corre-
sponding disubstituted alkynes 15±24.
in petroleum ether *60±808C) as the eluent. Finally the
product were crystallised from CHCl3.
1.2.1. 2-ꢀ3-Hydroxy-3-phenyl)-prop-1-ynyl benzyl alco-
hol 15. White powder *CHCl3), mp 988C. IR *KBr): nˆ
1
3265, 1600, 1490, 1479, 1446 cm21. H NMR *300 MHz,
In conclusion, we have described a very convenient and
general method for the synthesis of *E)-3-alkylidene-
isobenzofuran-1-*3H)-ones *phthalides). The method is
characterised by *i) easy availability of inexpensive starting
materials, *ii) use of non-toxic reagents and *iii) simple
operational procedures *a two step reaction). The present
method is complementary to the method which we have
described for the synthesis of *Z)-3-alkylidene-isobenzo-
furan-1-*3H)-ones.13
CDCl3): dˆ7.25±7.60 *m, 9H, Ar±H), 5.68 *s, 1H, CHOH),
4.78 *s, 2H, ±CH2). 13C NMR *75.5 MHz, CDCl3): dˆ
142.9, 132.8, 129.4, 129.1, 128.9, 128.0, 127.9, 127.0,
94.0, 84.1, 65.4, 64.3. UV *EtOH): lmax *log 1)ˆ254
*4.11), 245 *4.18), 211 *4.36). Anal. Calcd for
C16H14O2:C, 80.67; H, 5.88. Found: C, 80.34; H, 5.65.
1.2.2.
2-[3-Hydroxy-3-ꢀo-methylphenyl)]-prop-1-ynyl
benzyl alcohol 16. White powder *CHCl31light petroleum
ether), mp 1348C. IR *KBr) nˆ3294, 3138, 1602,1483,
1
1461 cm21. H NMR *300 MHz, CDCl31DMSO-d6): dˆ
7.20±7.73 *m, 8H, Ar±H), 5.87 *s, 1H, CHOH), 4.80 *s,
2H, ±CH2), 2.50 *s, 3H, CH3). 13C NMR *75.5 MHz,
CDCl3): dˆ143.5, 139.3, 135.5, 132.4, 130.9, 129.0,
128.6, 127.4, 126.4, 126.3, 126.2, 125.9, 93.4, 83.0, 64.5,
62.9, 18.9. UV *EtOH): lmax *log 1)ˆ287 *2.88), 255
*4.26), 246 *4.32), 212 *4.47). Anal. Calcd for C17H16O2:
C, 80.95; H, 6.35. Found: C, 80.72; H, 6.71.
1. Experimental
1.1. General
Melting points were determined in open capillary tubes on
Gallenkamp *England) and in sulphuric acid bath and on a
Reichert *285980) *Austria) melting point apparatus and are
uncorrected. UV spectra were recorded on a Hitachi 200-20
spectrometer using spectrophotometric grade ethanol
*Baker). IR spectra were taken on a Perkin±Elmer 298
1.2.3. 2-[3-Hydroxy-3-ꢀm-methyl phenyl)]-prop-1-ynyl
benzyl alcohol 17. White solid *CHCl3), mp 798C. IR
1
*KBr): nˆ3267, 3128, 1604, 1481, 1446 cm21. H NMR
1
instrument for samples as KBr plates or liquid ®lms. H
*300 MHz, CDCl3): dˆ7.08±7.41 *m, 8H, Ar±H), 5.55 *s,
1H, CHOH), 4.69 *s, 2H, CH2), 2.32 *s, 3H, ±CH3). 13C
NMR *75.5 MHz, CDCl3) dˆ145.1, 143.2, 141.0, 135.0,
131.9, 131.5, 131.2, 130.5, 130.2, 130.1, 126.4, 123.9,
96.5, 86.5, 67.3, 66.3, 24.1. UV *EtOH): lmax *log 1)ˆ
287 *2.75), 254 *4.23), 246 *4.29), 212 *4.44). Anal. Calcd
for C17H16O2: C, 80.95; H, 6.35. Found: C, 80.76; H, 6.56.
NMR spectra were recorded on a Varian EM-360, a Varian
XL-200 and a Bruker DPX-300 spectrometer for samples as
indicated with tetramethylsilane as internal reference. 13C
Spectra *75.5 MHz) were obtained on a Bruker DPX-300
spectrometer. Chemical shifts are reported in d unit *ppm); J
values given in Hz; splitting patterns are designated as
follows: s, singlet; d, doublet; t, triplet; q, quartet, m, multi-
plet; and br, broad. Analytical thin-layer chromatography
*TLC) was performed on precoated 0.2 mm. silica gel
60F-254 *E. Merck), and the spots were visualised with
UV light. Column chromatography was done on silica gel
*60±120 mesh) or neutral alumina. Elemental analyses *C,
H, N) were carried out on Perkin±Elmer 240C analyser.
2-Iodobenzylalcohol and palladium catalyst were commer-
cially available *Aldrich Chem. Co.). Acetylenic carbinols
were synthesised by the procedure of Jones et al.28 starting
from the corresponding aldehyde.
1.2.4. 2-[3-Hydroxy-3-ꢀp-methyl phenyl)]-prop-1-ynyl
benzyl alcohol 18. White powder *CHCl31light petroleum
ether), mp 1178C. IR *KBr): nˆ3307, 3188, 1512, 1477,
1
1450, 1417 cm21. H NMR *300 MHz, CDCl3): dˆ7.19±
7.50 *m, 8H, Ar±H), 5.66 *s, 1H, CHOH), 4.79 *s,
2H, ±CH2), 2.36 *s, 3H, CH3). 13C NMR *75.5 MHz,
CDCl3) dˆ142.6, 138.4, 137.7, 132.4, 129.4, 129.0,
127.6, 126.6, 120.9, 93.9, 84.0, 65.0, 63.9, 21.2. UV
*EtOH): lmax *log 1)ˆ254 *4.22), 245 *4.28), 211 *4.29).
Anal. Calcd for C17H16O2: C, 80.95; H, 6.35. Found: C,
80.60; H, 6.40.
1.2. Synthesis of disubstituted alkynes 15±24
1.2.5. 2-[3-Hydroxy-3-ꢀo-methoxy phenyl)]-prop-1-ynyl
benzyl alcohol 19. Colourless small needles *CHCl3), mp
1068C. IR *KBr): nˆ3271, 1602, 1589, 1494, 1465,
General procedure: A mixture of 2-iodobenzyl alcohol 4
*1 mmol), bis*triphenylphosphine) palladium*II)chloride
*5 mol%), CuI *8.0 mol%) in triethylamine *5 mL) and
DMF *2.5 mL) was stirred under nitrogen atmosphere for
1 h. Then acetylenic carbinol 5±14 *1.2±1.5 mmol) was
added to the reaction mixture. The solution was stirred at
rt for 24 h. Then the mixture was evaporated to dryness
under reduced pressure and the residue was extracted
with chloroform *3£50 mL). The combined organic layers
were washed with distilled water *3£50 mL), dried over
anhydrous Na2SO4, ®ltered and concentrated under low
pressure to give a residue. The crude mass was puri®ed by
column chromatography on neutral alumina to afford the
pure disubstituted alkyne 15±24 using 50% ethyl acetate
1440 cm21
.
1H NMR *300 MHz, CDCl3): dˆ6.88±7.58
*m, 8H, Ar±H), 5.88 *s, 1H, CHOH), 4.73 *s, 2H, ±CH2),
3.86 *s, 3H, ±OCH3). 13C NMR *75.5 MHz, CDCl3): dˆ
157.0, 143.2, 132.7, 130.2, 129.2, 129.1, 128.3, 127.9,
127.8, 121.5, 121.4, 111.3, 93.9, 83.8, 64.2, 62.0, 56.0.
UV *EtOH): lmax *log 1)ˆ274 *3.58), 246 *4.21), 211
*4.43). Anal. Calcd for C17H16O3: C, 76.11; H, 5.97.
Found: C, 75.72; H, 6.04.
1.2.6. 2-[3-Hydroxy-3-ꢀm-methoxy phenyl)]-prop-1-ynyl
benzyl alcohol 20. White solid *CHCl3), mp 908C. IR
*KBr): nˆ3251, 3116, 1606, 1587, 1485, 1452,

9478
R. Mukhopadhyay, N. G. Kundu / Tetrahedron 57 .2001) 9475±9480
1433 cm21. 1H NMR *300 MHz, CDCl3): dˆ6.79±7.39 *m,
8H, Ar±H), 5.55 *s, 1H, CHOH), 4.68 *s, 2H, ±CH2), 3.73
*s, 3H, ±OCH3). 13C NMR *75.5 MHz, CDCl3): dˆ 160.1,
142.8, 132.7, 130.0, 129.3, 128.3, 127.9, 121.6, 119.5,
114.4, 113.6, 112.4, 94.1, 84.3, 65.0, 63.9, 55.6. UV
*EtOH): lmax *log 1)ˆ275 *3.50), 246 *4.25), 211 *4.47).
Anal. Calcd for C17H16O3:C, 76.11; H, 5.97. Found: C,
76.34; H, 6.26.
were washed with saturated NaHCO3 solution and distilled
water, dried over anhydrous Na2SO4. Evaporation of the
ether layer yielded yellow solid which was puri®ed by
chromatography on silica gel *60±120 mesh) using 80%
CHCl3 in petroleum ether *60±808C) as the eluent. The
material was further puri®ed by crystallisation from a
mixture of CHCl3 and light petroleum ether.
1.3.1. ꢀE)-3-ꢀ20-Oxo-20-phenyl)ethylidene isobenzofuran-
1ꢀ3H)-one 25. White solid *CHCl31light petroleum ether),
mp 1348C, *lit. 118±1198C).26 IR *KBr): nˆ1786, 1670,
1.2.7. 2-[3-Hydroxy-3-ꢀp-methoxy phenyl)]-prop-1-ynyl
benzyl alcohol 21. White solid *CHCl3), mp 1028C. IR
*KBr): nˆ3363, 3066, 1610, 1510, 1483, 1452,
1
1612, 1469, 1448 cm21. H NMR *CDCl3, 300 MHz): dˆ
1419 cm21
.
1H NMR *300 MHz, CDCl3): dˆ6.78±7.45
8.96 *d, 1H, Jˆ9 Hz, Ar±C4±H), 7.43±8.08 *m, 8H, Ar±
H), 7.13 *s, 1H, vCH). 13C NMR *75.5 MHz, CDCl3): dˆ
189.8, 166.3, 158.3, 138.7, 136.7, 135.8, 133.8, 130.1,
129.3, 129.0, 128.9, 128.7, 128.2, 127.1, 125.8, 106.6. UV
*CHCl3): lmax *log 1)ˆ324 *3.87), 299 *3.89), 287 *3.92),
246 *4.04). Anal. Calcd for C16H10O3:C, 76.80; H, 4.00.
Found: C, 76.98; H, 4.02.
*m,, 8H, Ar±H), 5.54 *s, 1H, CHOH), 4.73 *s, 2H, ±CH2),
3.73 *s, 3H, ±OCH3). 13C NMR *75.5 MHz, CDCl3):
dˆ160.0, 142.8, 133.4, 132.7, 129.2, 128.5, 128.2,
127.8, 121.6, 114.3, 94.3, 84.2, 64.7, 63.9, 55.7. Anal.
Calcd for C17H16O3: C, 76.11; H, 5.97. Found: C, 75.92;
H, 5.73.
1.3.2. ꢀE)-3-ꢀ20-o-Methylphenyl-20-oxo)ethylidene iso-
benzofuran-1ꢀ3H)-one 26. White small needles
*CHCl31light petroleum ether), mp 1028C. IR *KBr): nˆ
1.2.8. 2-[3-Hydroxy-3-ꢀp-¯uoro phenyl)]-prop-1-ynyl
benzyl alcohol 22. White solid *CHCl31light petroleum
ether), mp 1048C. IR *KBr): nˆ3263, 3116, 1604, 1506,
1
1479, 1448, 1407 cm21. H NMR *300 MHz, CDCl3) dˆ
1
1799, 1670, 1616, 1585, 1471 cm21. H NMR *300 MHz,
7.07±7.56 *m, 8H, Ar±H), 5.66 *s, 1H, CHOH), 4.78 *s, 2H,
±CH2). 13C NMR *75.5 MHz, CDCl3) dˆ146.0, 132.8,
129.5, 128.9, 128.8, 128.1, 116.1, 115.8, 94.2, 84.6, 64.7,
64.3. UV *EtOH): lmax *log 1)ˆ254 *4.22), 245 *4.28), 210
*4.47). Anal. Calcd for C16H13FO2: C, 75.0; H, 5.07. Found:
C, 74.89; H, 4.86.
CDCl3): dˆ9.03 *d, 1H, Jˆ9 Hz, Ar±C4±H), 7.26±8.01
*m, 7H, Ar±H), 6.94 *s, 1H, vCH), 2.58 *s, 3H, ±CH3).
13C NMR *75.5 MHz, CDCl3): dˆ193.7, 166.3, 157.6,
139.5, 138.4, 136.7, 135.8, 135.4, 133.3, 132.3, 132.1,
129.2, 128.0, 127.1, 126.3, 110.0, 21.3. UV *EtOH): lmax
*log 1)ˆ325 *4.12), 300 *4.11), 290 *4.08), 249 *3.92).
Anal. Calcd for C17H12O3: C, 77.27; H, 4.54. Found: C,
76.94; H, 4.32.
1.2.9. 2-[3-Hydroxy-3-ꢀp-chloro phenyl)]-prop-1-ynyl
benzyl alcohol 23. White solid *CHCl31light petroleum
ether), mp 1058C. IR *KBr): nˆ3280, 3097, 1593,
1483, 1454, 1407 cm21 1H NMR *300 MHz, CDCl3)
.
dˆ7.26±7.54 *m, 8H, Ar±H), 5.68 *s, 1H, CHOH), 4.79
*s, 2H, ±CH2). 13C NMR *75.5 MHz, CDCl3) dˆ146.2,
132.8, 129.6, 129.2, 128.4, 128.1, 128.0, 116.2, 115.8,
94.2, 83.5, 64.7, 64.3. UV *EtOH): lmax *log 1)ˆ255
*4.28), 245 *4.34), 224 *4.19), 211 *4.48). Anal. Calcd
for C16H13ClO2: C, 70.45; H, 4.77. Found: C, 70.62;
H, 4.74.
1.3.3. ꢀE)-3-ꢀ20-m-Methylphenyl-20-oxo)ethylidene iso-
benzofuran-1ꢀ3H)-one 27. Yellowish gum. IR *KBr):
nˆ1791, 1662, 1600, 1583, 1471,1456 cm21
.
1H NMR
*300 MHz, CDCl3): dˆ9.03 *d, 1H, Jˆ9 Hz, Ar±C4±H),
7.26±8.01 *m, 7H, Ar±H), 7.21 *s, 1H, vCH), 2.46 *s,
3H, ±CH3). 13C NMR *75.5 MHz, CDCl3): dˆ190.1,
139.1, 136.7, 135.8, 134.6, 133.2, 129.3, 129.1, 128.1,
126.0, 125.8, 106.9, 21.8. Anal. Calcd for C19H12O3: C,
77.27; H, 4.54. Found: C, 76.98; H, 4.26.
1.3.4. ꢀE)-3-ꢀ20-p-Methylphenyl-20-oxo)ethylidene iso-
benzofuran-1ꢀ3H)-one 28. Light yellow crystalline solid
*CHCl31light petroleum ether), mp 1388C, IR *KBr):
1.2.10. 2-[3-Hydroxy-3-ꢀ3,4-methylenedioxy) phenyl]-
prop-1-ynyl benzyl alcohol 24. Yellowish solid *CHCl3),
mp 838C. IR *KBr): nˆ3265, 3136, 1504, 1488, 1438, 1402,
1357 cm21. 1H NMR *300 MHz, CDCl3): dˆ6.71±7.39 *m,
8H, Ar±H), 5.87 *s, 2H, O±CH2±O), 5.47 *s, 1H, CHOH),
4.67 *s, 2H, ±CH2). 13C NMR *75.5 MHz, CDCl3): dˆ
148.2, 147.9, 142.7, 134.1, 132.7, 129.2, 128.2, 127.9,
121.5, 120.8, 108.5, 107.9, 101.6, 94.1, 84.3, 64.9, 63.8.
Anal. Calcd for C17H14O4: C, 72.34; H, 4.96. Found: C,
72.72; H, 5.02.
1
nˆ1786, 1662, 1614, 1598, 1583, 1471 cm21. H NMR
*300 MHz, CDCl3): dˆ9.01 *d, 1H, Jˆ9 Hz, Ar±C4±H),
7.29±7.98 *m, 7H, Ar±H), 7.18 *s, 1H, vCH), 2.43 *s,
3H, ±CH3).13C NMR *75.5 MHz, CDCl3): dˆ189.3,
166.3, 157.9, 144.8, 136.7, 136.2, 135.7, 133.1, 129.9,
128.9, 128.7, 128.1, 127.1, 125.7, 106.8, 22.1. UV
*EtOH): lmax *log 1)ˆ329 *4.07), 301 *4.01), 287 *4.02),
266 *4.05), 243 *3.95). Anal. Calcd for C17H12O3: C, 77.27;
H, 4.54. Found: C, 77.35; H, 4.83.
1.3. Preparation of 3-alkylidene isobenzofuran-1ꢀ3H)-
ones 25±34
1.3.5. ꢀE)-3-ꢀ20-o-Methoxyphenyl-20-oxo)ethylidene iso-
benzofuran-1ꢀ3H)-one 29. Light yellow small needles
*CHCl31light petroleum ether), mp 1258C. IR *KBr):
General procedure: To a solution of the disubstituted
alkynes 15±24 *200 mg) in acetone *10 mL), a solution of
CrO3 in water and concentrated H2SO4 *5 mL) was slowly
added at 08C under N2 atmosphere and stirred for 2±3 h.
Then the mixture was diluted with chilled water and the
product was extracted with ether. The combined extracts
nˆ1792, 1655, 1600, 1470 cm21
.
1H NMR *300 MHz,
CDCl3) dˆ9.04 *d, 1H, Jˆ9 Hz, Ar±C4±H), 7.41±7.90
*m, 7H, Ar±H), 7.15 *s, 1H, vCH), 3.80 *s, 3H, ±OCH3).
13C NMR *75.5 MHz, CDCl3) dˆ190.5, 165.8, 158.6,

R. Mukhopadhyay, N. G. Kundu / Tetrahedron 57 .2001) 9475±9480
9479
156.4, 136.6, 135.9, 134.4, 133.6, 132.6, 130.6, 127.6,
126.0, 125.3, 120.9, 111.6, 111.5, 55.8. Anal. Calcd
for C17H12O4: C, 72.85; H, 4.28. Found: C, 72.53; H,
4.45.
125.0, 108.1, 106.4, 102.1. Anal. Calcd for C17H10O5: C,
69.38, H, 3.42. Found: C, 69.05; H, 3.62.
1.4. Preparation of ꢀZ)-3-ꢀ20-aryl-20-oxo)ethylidene iso-
benzofuran-1ꢀ3H)-ones 35±38from the corresponding
ꢀE)-isomer 25, 28, 32, 33 through isomerisation. A typical
procedure
1.3.6. ꢀE)-3-ꢀ20-m-Methoxyphenyl-20-oxo)ethylidene iso-
benzofuran-1ꢀ3H)-one 30. Light yellow needles *CHCl31
light petroleum ether), mp 1418C. IR *KBr): nˆ1796, 1668,
1
1618, 1595, 1585, 1487, 1471 cm21. H NMR *300 MHz,
1.4.1. ꢀZ)-3-ꢀ20-Oxo-20-phenyl)ethylidene isobenzofuran-
1ꢀ3H)-one 35. The *E)-isobenzofuranone 22 *100 mg) was
dissolved in 96% sulphuric acid *2 mL) and stirred at room
temperature for 2.5 h. Crushed ice was added to the mixture
and it was ®ltered. The residue was washed with water
*3£10 mL), saturated solution of NaHCO3 *2£10 mL) and
then water *2£10 mL). The product was crystallised from
CHCl31light petroleum ether) to afford colourless small
needles, mp 1628C *lit. 1688C),26 *lit. 163±1648C).13 IR
CDCl3): dˆ9.04 *d, 1H, Jˆ9 Hz, Ar±C4±H), 7.27±8.00
*m, 7H, Ar±H), 7.18, *s, 1H, vCH), 3.90 *s, 3H,
±OCH3). 13C NMR *75.5 MHz, CDCl3): dˆ189.6, 166.2,
160.4, 158.3, 140.1, 135.8, 133.3, 130.4, 128.1, 126.2,
125.8, 122.5, 121.4, 120.5, 112.8, 106.7, 55.9. UV
*EtOH): lmax *log 1)ˆ320 *4.06), 301 *4.07), 292 *4.04),
252 *3.92). Anal. Calcd for C17H12O4: C, 72.85; H, 4.28.
Found: C, 73.10; H, 4.66.
1
*KBr): nˆ1776, 1674, 1641, 1593, 1469 cm21. H NMR
1.3.7. ꢀE)-3-ꢀ20-p-Methoxyphenyl-20-oxo)ethylidene iso-
benzofuran-1ꢀ3H)-one 31. Colourless small needles
*CHCl31light petroleum ether), mp 1658C, *lit. 1638C)27
*300 MHz, CDCl3): dˆ7.27±8.02 *m, 9H, Ar±H), 6.79 *s,
1H, vCH). 13C NMR *75.5 MHz, CDCl3) dˆ188.9, 153.5,
139.6, 138.5, 135.4, 134.8, 134.5, 133.6, 132.8, 130.9,
129.0, 126.5, 125.9, 125.3, 125.0, 121.6, 100.5. UV
*CHCl3): lmax *log 1)ˆ321 *4.14), 299 *4.17), 288 *4.15),
248 *4.06).
IR *KBr): nˆ1793, 1656, 1596, 1568, 1510, 1456 cm21
.
1H NMR *300 MHz, CDCl3): dˆ8.99 *d, 1H, Jˆ9 Hz,
Ar±C4±H), 7.26±8.13 *m, 7H, Ar±H), 7.18 *s, 1H,
vCH), 3.89 *s, 3H, ±OCH3). 13C NMR *75.5 MHz,
CDCl3): dˆ174.9, 165.6, 164.2, 157.6, 135.7, 133.1,
132.6, 131.7, 131.2, 129.8, 128.1, 127.1, 125.7, 114.6,
106.9, 56.1, 55.9. Anal. Calcd for C17H12O4: C, 77.26; H,
4.57. Found: C, 77.30; H, 4.73.
1.4.2. ꢀZ)-3-ꢀ20-p-Methylphenyl-20-oxo)ethylidene iso-
benzofuran-1ꢀ3H)-one 36. Yellow crystalline solid
*CHCl31petroleum ether); mp 2088C, *lit. 2058C)27 IR
*KBr): nˆ1782, 1668, 1616, 1473 cm21
.
1H NMR
*300 MHz, CDCl3): dˆ7.26±8.00 *m, 8H, Ar±H), 6.75 *s,
1H, vCH), 2.44 *s, 3H, ±CH3). 13C NMR *75.5 MHz,
CDCl3): dˆ188.5, 153.0, 144.6, 139.7, 136.0, 135.3,
132.6, 129.7, 129.2, 128.6, 126.4, 125.3, 121.5, 100.8,
22.1. Anal. Calcd for C17H12O3; C, 77.27; H, 4.54. Found:
C, 76.93; H, 4.24.
1.3.8. ꢀE)-3-ꢀ20-p-Fluorophenyl-20-oxo)ethylidene iso-
benzofuran-1ꢀ3H)-one 32. Light yellow solid *CHCl31
light petroleum ether), mp 1558C, *lit. 155±1578C)23a IR
1
*KBr): nˆ1795, 1674, 1625, 1593, 1504, 1473 cm21. H
NMR *300 MHz, CDCl3): dˆ9.02 *d, 1H, Jˆ9 Hz, Ar±
C4±H), 7.17±8.10 *m, 7H, Ar±H), 7.16 *s, 1H, vCH).
13C NMR *75.5 MHz, CDCl3): dˆ188.2, 168.0, 164.6,
158.5, 136.6, 135.8, 133.3, 131.5, 131.4, 130.7, 128.2,
127.1, 125.9, 116.5, 116.0, 106.2. UV *EtOH): lmax
*log 1)ˆ327 *4.20), 303 *4.19), 250 *3.91). Anal.
Calcd for C16H9FO3: C, 71.64; H, 3.35. Found: C, 71.63;
H, 3.25.
1.4.3. ꢀZ)-3-ꢀ20-p-Fluorophenyl-20-oxo)ethylidene iso-
benzofuran-1ꢀ3H)-one 37. Light yellow crystals
*CHCl31 light petroleum ether), mp 1838C. IR *KBr):
1
nˆ1782, 1674, 1624, 1587, 1508, 1473 cm21; H NMR
*300 MHz, CDCl3) dˆ7.13±8.06 *m, 8H, Ar±H), 6.73 *s,
1H, vCH). 13C NMR *75.5 MHz, CDCl3) dˆ187.4, 167.9,
166.1, 164.5, 153.5, 139.5, 135.5, 134.9, 132.8, 131.7,
131.6, 126.5, 121.6, 116.3, 116.0, 100.3. Anal. Calcd for
C16H9FO3: C, 71.64; H, 3.35. Found: C, 71.28; H, 3.02.
1.3.9. ꢀE)-3-ꢀ20-p-Chlorophenyl-20-oxo)ethylidene iso-
benzofuran-1ꢀ3H)-one 33. Light yellow solid *CHCl31
light petroleum ether), mp 1618C, *lit. 165±1678C)27 IR
1
*KBr): nˆ1799, 1670, 1614, 1585, 1471 cm21. H NMR
1.4.4. ꢀZ)-3-ꢀ20-p-Chlorophenyl-20-oxo)ethylidene iso-
benzofuran-1ꢀ3H)-one 38. Yellowish small needles
*CHCl31light petroleum), mp 2008C, *lit. 202±2038C)27
*300 MHz, CDCl3): dˆ9.03 *d, 1H, Jˆ9 Hz, Ar±C4±H),
7.27±8.00 *m, 7H, Ar±H), 7.15 *s, 1H, vCH). 13C NMR
*75.5 MHz, CDCl3): dˆ188.5, 166.1, 158.7, 140.3, 137.1,
136.5, 135.8, 133.4, 130.4, 130.1, 129.5, 129.3, 128.2,
127.1, 125.9, 106.1. UV *EtOH): lmax *log 1)ˆ330 *4.28),
305 *4.24), 249 *3.96). Anal. Calcd for C16H9ClO3: C,
64.49; H, 3.16. Found: C, 64.24; H, 2.95.
IR *KBr): nˆ1780, 1660, 1610, 1460 cm21
.
1H NMR
*300 MHz, CDCl3): dˆ7.27±8.02 *m, 8H, Ar±H), 6.70 *s,
1H, vCH).13C NMR *75.5 MHz, CDCl3): dˆ187.8, 140.2,
140.1, 136.8, 135.5, 132.9, 130.4, 129.4, 126.6, 125.3,
121.7, 100.2. Anal. Calcd for C16H9ClO3: C, 64.49; H,
3.16. Found: C, 64.29; H, 2.98.
1.3.10.
ꢀE)-3-[20-ꢀ3,4-Methylenedioxy)phenyl-20-oxo]-
ethylidene isobenzofuran-1ꢀ3H)-one 34. Light yellow
small needles *CHCl31light petroleum ether), mp 1718C.
IR *KBr): nˆ1790, 1660, 1620 cm21. 1H NMR *300 MHz,
CDCl3): dˆ8.89 *d, 1H, Jˆ9 Hz, Ar±C4±H), 7.45±7.90
*m, 6H, Ar±H), 7.05 *s, 1H, vCH), 6.00 *s, 2H, O±CH2±
O) 13C NMR *75.5 MHz, CDCl3) dˆ187.4, 165.9, 157.4,
152.2, 136.3, 135.3, 133.3, 132.7, 127.6, 126.8, 125.4,
Acknowledgements
Grateful acknowledgement is made of the award of a Senior
Research Fellowship to R. M. by the Council of Scienti®c
and Industrial Research, New Delhi, India.

9480
R. Mukhopadhyay, N. G. Kundu / Tetrahedron 57 .2001) 9475±9480
15. *a) Kundu, N. G.; Pal, M.; Mahanty, J. S.; Das, P.; Das, B.
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