Syntheses and regiochemistry of enol addition to 9-phenyl-9H-xanthen-9-ol

Article abstract of DOI:10.1016/j.tet.2008.02.053

Regioselective C-C bond formation of 9-phenyl-9H-xanthen-9-ol 1 with various enolizable ketones I-X in an acidic (HBr) medium, obtained by the reaction of 1,1′-(ethane-1,2-diyl)dipyridinium bistribromide (EDPBT) with ketone is observed. Except for ketone,

Full text of DOI:10.1016/j.tet.2008.02.053

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Tetrahedron 64 (2008) 3960e3965
www.elsevier.com/locate/tet
Syntheses and regiochemistry of enol addition
to 9-phenyl-9H-xanthen-9-ol
*
Veerababurao Kavala, Siva Murru, Gopal Das, Bhisma K. Patel
Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati 781 039, India
Received 7 January 2008; received in revised form 14 February 2008; accepted 15 February 2008
Available online 21 February 2008
Abstract
Regioselective CeC bond formation of 9-phenyl-9H-xanthen-9-ol 1 with various enolizable ketones IeX in an acidic (HBr) medium,
obtained by the reaction of 1,10-(ethane-1,2-diyl)dipyridinium bistribromide (EDPBT) with ketone is observed. Except for ketone, 4-methyl-
pentan-2-one VII in all other cases examined the attack to xanthenyl carbocation is from the thermodynamically stable enolizable side of
the unsymmetrical ketones. In the case of 3-methyl-butan-2-one VIII the equilibrium is in favor of the more stable enolizable ketone, which
has large steric factor, hence no reaction was observed during its addition to alcohol 1.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
ethane (DPTBE), which is found to be superior to all known or-
ganicammonium tribromides.6 This compound is renamed as
1,10-(ethane-1,2-diyl)dipyridinium bistribromide (EDPBT)
and is an excellent catalyst for acylation of alcohols using acetic
anhydrides and reagent for the formation of thiazolylidene
derivatives and 1,4-dithiins.7
Xanthene derivatives are useful pharmaceuticals such as
muscarinic receptor antagonist,1a cancer chemotherapy,1b try-
panothione reductase inhibitor,1c chemosensitizers against
chloroquine-resistant Plasmodium falciparum,1d nonpeptidic
inhibitors,1e mGluR1 enhancer,1f,g and CCR1 antagonist.1h,i
They are also useful as dyes,2a,b photosensitizers,2cee ligand
for asymmetric catalysis3 and have the propensity to form in-
clusion compounds with various aromatic compounds and
form self assembled superstructures.4 Thus, syntheses of xan-
thene derivatives are of immense interest. Various multi car-
bon homologations 1ae1j of 9-phenyl-9H-xanthen-9-ol 1
were obtained through a CeC bond formation by reacting it
with various enolizable ketones in an acidic medium. Here
we report the syntheses of various enol additions to xanthene.
In addition to their syntheses we were interested in factors re-
sponsible for the regiochemistry of various addition products.
Tetrabutylammonium tribromide in an organic medium is an
excellent source of anhydrous HBr, which has been utilized for
various important organic transformations in our laboratory.5
Recently we have developed 1,2-dipyridiniumditribromide-
2. Results and discussion
In an attempt to acetylate 9-phenyl-9H-xanthen-9-ol 1 em-
ploying acetic anhydride in acetone and 1,10-(ethane-1,2-diyl)-
dipyridinium bistribromide (EDPBT) as catalyst7a gave no
trace of acetylated product, rather an unusual three-carbon
homologation 1a was observed (Table 1, Scheme 1). Being
buoyant by this result we focused our attention to synthesize
various xanthene analogues. Reaction of xanthydrol, thioxan-
thydrol, and 9,10-dihydro-10-methyl-9-acrydenol with N-
vinylacetamide or ethylvinylether as acetaldehyde anion
equivalents has been reported.8 Formation of the product
1-(9-phenyl-9H-xanthen-9-yl)-propan-2-one 1a could be
explained through a carbocation intermediate, obtained by the
initial reaction of tertiary alcohol 1 with HBr generated by
the reaction of EDPBT with acetone, which undergoes nucleo-
philic attack by the enolized acetone (Scheme 1). In this reac-
tion acetic anhydride acts as a dehydrating agent by reacting
* Corresponding author.
E-mail address: patel@iitg.ernet.in (B.K. Patel).
0040-4020/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.02.053

V. Kavala et al. / Tetrahedron 64 (2008) 3960e3965
3961
Table 1
CeC bond formation at the tertiary carbon of 9-phenyl-9H-xanthen-9-ol with ketonesa
Substrate
Ketone
Productb
Time (h)
12
Yieldc (%)
Ph
Ph
O
O
(I)
(1a)
87
O
Ph
O
O
(II)
(1b)
24
18
18
81
80
77
Ph
O
O
Ph
Ph
(III)
(1c)
O
O
O
O
(IV)
(1d)
O
Ph
Ph
O
Ph
O
(V)
(1e)
24
24
72
79
Ph
Ph
Ph
OH
O
(1)
Ph
O
O
O
(VI)
(1f)
O
O
Ph
O
(VII)
(1g)
24
12
60
35
O
O
O
O
O
O
Ph
(1h)d
(VIII)
O
Ph
Ph
O
(IX)
(1i)
24
12
78
75
Ph
O
O
O
Ph
O
O
O
(X)
(1j)
OEt
O
a
Reactions were monitored by TLC.
b
c
d
Products were characterized by IR, 1H, 13C NMR.
Yields of the isolated product.
Obtained due to the contamination of hydroperoxide.

3962
V. Kavala et al. / Tetrahedron 64 (2008) 3960e3965
with the water generated in the reaction medium to yield acetic
acid, which further facilitates the reaction by making the me-
dium further acidic.
the product is governed by the formation of a stable enol, giving
3-(9-phenyl-9H-xanthen-9-yl)-butan-2-one 1f exclusively. This
observation is, however, inconsistent with the observation made
by others, where the product obtained is by the attack of
the methyl carbon of butan-2-one.9 The difference in the ob-
served regiochemistry may be due to difference in the xanthene
system, 1,8-dimethoxy-9H-xanthene-9-ol instead of 9-phenyl-
9H-xanthen-9-ol 1. Interestingly, kinetically controlled enol
additionproduct4-methyl-1-(9-phenyl-9H-xanthen-9-yl)-pentan-
2-one 1g was observed when unsymmetrical and one side steri-
cally hindered ketone, 4-methyl-pentan-2-one VII, was used
(Table 1). In this case even though enolization is expected to fa-
vor toward a thermodynamically stable form, the attack is pos-
sible only from the less hindered enolizable side, due to the large
steric hindrance caused by the adjacent isopropyl group (Fig. 1).
The single crystal XRD structure of the product 1g is reported,
which exhibits interesting CeH/O type hydrogen bonding
network.4c
+
-
Br3
+
Br-
N
N
-
N
+
N
+
Br-
Br3
EDPBT
EDPDB
+
O
O
Br
HBr
+
R
R
+
O
O
O
+
HBr
Ph
OH
O
H
Ph
Ph
R
H
R
O
H
O
O
Ph
However, neither of the above observations has been mani-
fested during the reaction of 3-methyl-butan-2-one VIII with
1 under an identical condition. X-ray crystallographic analysis
of product showed a molecular oxygen insertion (Fig. 2) from
the more hindered side of the enolized ketone VIII giving the
O
R
Scheme 1. Proposed mechanism of CeC bond formation.
The scope of the reaction was extended further by replacing
acetone with other enolizable ketones such as acetophenone II,
which gave 1b as the exclusive product (Table 1). Cyclic ali-
phatic ketones such as cyclohexanone III and cyclopentanone
IV gave the corresponding addition products 1c and 1d, respec-
tively, in good yields in a relatively shorter reaction time.
Other symmetrical ketone, 1,3-diphenyl-propan-2-one V
also gave the expected product 1e (Table 1).
In the case of ketone II the enolization is possible only
from one side and in all other cases (IIIeV) due to their sym-
metrical nature the same enol is formed whether enolization is
from the left side or from the right.
Reaction of an unsymmetrical ketone such as butan-2-one
VI, under a similar condition gave 3-(9-phenyl-9H-xanthen-9-
yl)-butan-2-one 1f as the sole product, which was obtained
through the attack of methylene carbon rather than methyl
carbon. In spite of the steric hindrance, the regioselectivity of
Figure 2. An ORTEP view with the atomic numbering scheme of 1h.
Figure 1. View showing the steric environment in ketone VII. (a) Enolization towards more substituted side; (b) enolization towards less substituted side.

V. Kavala et al. / Tetrahedron 64 (2008) 3960e3965
3963
molecular oxygen inserted product 1h. This can be explained
only if the reaction goes via a radical mechanism. No signal
for the radical couldbe detected when reaction was continuously
monitored by EPR spectrometer. It was found that formation of
the product 1h was due to the contamination of corresponding
hydroperoxide obtained by a radical auto-oxidation at the ter-
tiary carbon of VIII. When reaction was performed with
a freshly distilled ketone under a nitrogen atmosphere no reac-
tion occurred even after three days. This is because enolization
is expected to favor exclusively10 toward the more substituted
enol, which is sterically unfavorable for the attack on xanthenyl
carbocation. No kinetically controlled enol addition product
was observed due to the great stability of the highly substituted
enol in VIII.10
Bruker Smart Apex-II CCD diffractometer using graphite
˚
monochromated Mo Ka radiation (l¼0.71073 A) at 298 K.
Cell parameters were retrieved using SMART software and re-
fined with SAINT on all observed reflections. Data reduction
was performed with the SAINT software and corrected for
Lorentz and polarization effects. Absorption corrections
were applied with the program SADABS. The structure was
solved by direct methods implemented in SHELX-97 program
and refined by full-matrix least-squares methods on F2. All
non-hydrogen atomic positions were located in difference
Fourier maps and refined anisotropically. The hydrogen atoms
were placed in their geometrically generated positions. All the
colorless crystals were isolated in rectangular shape from ethyl
acetate and hexane mixture (8:2) at room temperature.
Two other unsymmetrical ketones viz. 1-phenyl-propan-2-
one IX and ethyl acetoacetate X were reacted with 1, giving
the products 1i and 1j, respectively (Table 1). The regiochemistry
of the product obtained corresponds to the attack by the
thermodynamically stable enol (Table 1). Ketone 1-phenyl-
propan-2-one IX gives exclusive thermodynamically con-
trolled product 1i whereas ketone 4-methyl-pentan-2-one
VII yielded kinetically controlled product 1g. In the case of
ketone IX the steric factor exhibited by a flat phenyl ring is
presumably much less compared to VII having an isopropyl
group with three tetrahedral carbon atoms, thereby giving en-
tirely kinetically controlled product.
4.2. General procedure
To 9-phenyl-9H-xanthen-9-ol (1.37 g, 5 mmol) in ketone
(5 mL) were added EDPBT (166 mg, 0.25 mmol) and acetic
anhydride (945 mL, 10 mmol). After the addition of the
EDPBT the color of the reaction mixture turned to red, inten-
sity of which increased after some time. Progress of the reac-
tion was monitored by TLC. Toward the completion of the
reaction the color intensity faded. The reaction mixture was
concentrated and admixed with ethyl acetate [product 1d
was extracted with CH2Cl2 (2ꢀ25 mL)]. Organic layer was
washed subsequently with saturated sodium bicarbonate solu-
tion (2ꢀ5 mL) and water (2ꢀ5 mL). The product was dried
over anhydrous Na2SO4 and crystallized from a mixture of
ethyl acetate/hexane (8:2) to yield the desired product. In
the case of 1d it was separated over neutral alumina column
using ethyl acetate/hexane as the eluent.
3. Conclusion
In conclusion, we have achieved multi carbon homologa-
tions of xanthene 1 through a CeC bond formation by various
enolizable ketones in an acidic medium. In most cases the re-
giochemistry of the product is governed by the attack of ther-
modynamically stable enol. But when the steric factor
dominates as is the case with 4-methyl-pentan-2-one VII prod-
uct obtained is via a kinetically controlled enol attack. With
further increase in steric hindrance as in 3-methyl-butan-2-
one VIII no reaction takes place.
4.3. Spectral data
4.3.1. 1-(9-Phenyl-9H-xanthen-9-yl)-propan-2-one (1a)
White solid, mp 139e140 ꢁC. Rf¼0.47 (EtOAc/hexane
2:98). IR (KBr): 3058, 3027, 2960, 2930, 1711, 1603, 1568,
1481, 1450, 1301, 1255, 1158, 1122, 1030, 892, 753,
4. Experimental
1
702 cmꢂ1. H NMR (400 MHz, CDCl3): d 1.72 (s, 3H), 3.51
(s, 2H), 6.81 (d, 2H, J¼7.6 Hz), 6.89 (t, 3H, J¼7.6 Hz), 7.07
(d, 2H, J¼8 Hz), 7.15 (t, 3H, J¼7.6 Hz), 7.25e7.27 (m,
3H). 13C NMR (100 MHz, CDCl3): d 31.3, 44.7, 55.8,
116.1, 122.9, 126.2, 126.5, 127.8, 128.0, 128.8, 148.9,
150.4, 205.3. HRMS (ESI): (MH)þ, found: 315.3906,
C22H18O2 requires: 315.3909.
4.1. General
All the reagents were commercial grade and purified ac-
cording to the established procedures. Organic extracts were
dried over anhydrous sodium sulfate. Solvents were removed
in a rotary evaporator under reduced pressure. Silica gel
(60e120 mesh size) was used for the column chromatography.
Reactions were monitored by TLC on silica gel 60 GF254
(0.25 mm). NMR spectra were recorded in CDCl3 or
DMSO-d6 with tetramethylsilane as the internal standard for
1H NMR (400 MHz) and CDCl3 or DMSO-d6 solvents as
internal standard for 13C NMR (100 MHz). IR spectra were
recorded in KBr or neat. GCeMS were recorded using
a capillary column (30ꢀ0.25 mmꢀ0.25 mm) in EI mode.
HRMS spectra were recorded in WATERS LC-MS/MS Sys-
tem, Q-Tof PremierÔ. Crystal Data were collected with
4.3.2. 1-Phenyl-2-(9-phenyl-9H-xanthen-9-yl)-ethanone (1b)
White solid, mp 186e188 ꢁC. Rf¼0.65 (EtOAc/hexane
2:98). IR (KBr): 3065, 3038, 2951, 2891, 1685, 1598, 1571,
1484, 1451, 1352, 1310, 1257, 1222, 1181, 1126, 1098,
1040, 974, 889, 774, 698 cmꢂ1
.
1H NMR (400 MHz,
CDCl3): d 4.12 (s, 2H), 6.84 (m, 3H), 7.09 (m, 4H), 7.31
(m, 9H), 7.70 (d, 2H, J¼7.2 Hz). 13C NMR (100 MHz,
CDCl3): d 45.3, 50.6, 116.4, 123.1, 126.6, 127.5, 127.9,
128.1, 128.4, 128.6, 129.0, 132.8, 137.6, 149.3, 151.2,

3964
V. Kavala et al. / Tetrahedron 64 (2008) 3960e3965
196.7. HRMS (ESI): (MH)þ, found: 377.4613, C27H20O2
requires: 377.4617.
131.7, 147.0, 150.5, 152.3, 210.5. HRMS (ESI): (MH)þ,
found: 329.4171, C23H20O2 requires: 329.4177.
4.3.3. rac-2-(9-Phenyl-9H-xanthen-9-yl)-cyclohexanone (1c)
White solid, mp 181e183 ꢁC. Rf¼0.51 (EtOAc/hexane
2:98). IR (KBr): 3066, 3031, 2930, 2857, 1711, 1596, 1571,
1475, 1440, 1308, 1276, 1240, 1124, 1095, 1035, 876, 758,
4.3.7. 4-Methyl-1-(9-phenyl-9H-xanthen-9-yl)-pentan-
2-one (1g)
White solid, mp 194e196 ꢁC. Rf¼0.57 (EtOAc/hexane
2:98). IR (KBr): 3050, 3037, 2966, 2879, 1711, 1603, 1578,
1486, 1450, 1404, 1368, 1312, 1260, 1235, 1126, 1062,
1
702 cmꢂ1. H NMR (400 MHz, CDCl3): d 1.54 (m, 3H), 1.80
(m, 1H), 1.98 (m, 1H), 2.15 (m, 1H), 2.23 (m, 1H), 2.33 (m,
1H), 3.48 (dd, 1H, J1¼5 Hz, J2¼12.8 Hz), 6.68 (d, 1H,
J¼8 Hz), 6.86 (m, 2H), 7.05 (m, 2H), 7.15 (m, 5H), 7.23
(m, 3H). 13C NMR (100 MHz, CDCl3): d 26.2, 28.4, 30.8,
44.3, 49.4, 61.4, 115.7, 116.0, 122.5, 126.0, 127.2, 127.7,
127.8, 127.9, 129.7, 130.1, 132.0, 147.1, 151.5, 151.8, 209.4.
HRMS (ESI): (MH)þ, found: 355.4550, C25H22O2 requires:
355.4555.
1040, 890, 750, 702 cmꢂ1 1H NMR (400 MHz, CDCl3):
.
d 0.63 (d, 6H, J¼5.2 Hz), 1.56 (br s, 1H), 1.85 (d, 2H), 3.46
(s, 2H), 6.78 (d, 2H, J¼8 Hz), 6.88 (t, 3H, J¼7.6 Hz), 7.06
(d, 2H, J¼8 Hz), 7.14 (m, 4H), 7.26 (d, 2H, J¼4.4 Hz). 13C
NMR (100 MHz, CDCl3): d 22.4, 24.2, 44.8, 53.2, 55.1,
116.1, 122.8, 126.2, 126.7, 127.7, 128.0, 128.2, 128.8,
149.1, 150.5, 207.0. HRMS (ESI): (MH)þ, found: 357.4709,
C25H24O2 requires: 357.4713.
4.3.4. rac-2-(9-Phenyl-9H-xanthen-9-yl)-cyclopentanone(1d)
White solid, mp 146e148 ꢁC. Rf¼0.65 (EtOAc/hexane
2:98). IR (KBr): 3056, 3031, 2964, 2878, 1736, 1598, 1572,
1477, 1444, 1403, 1305, 1239, 1153, 1097, 1039, 889, 754,
4.3.8. 3-Methyl-3-(9-phenyl-9H-xanthen-9-yl-peroxy)-
butan-2-one (1h)
White solid, mp 125e128 ꢁC. Rf¼0.55 (EtOAc/hexane
2:98). IR (KBr): 3054, 3036, 2996, 2983, 2927, 1710, 1601,
1573, 1476, 1449, 1352, 1319, 1293, 1251, 1219, 1164,
1
701 cmꢂ1. H NMR (400 MHz, CDCl3): d 1.66 (m, 4H), 2.18
(br s, 2H), 3.36 (t, 1H, J¼9.2 Hz), 6.67 (d, 1H, J¼8 Hz), 6.87
(t, 2H, J¼8 Hz), 6.93 (d, 1H, J¼8 Hz), 7.09 (m, 3H), 7.20 (m,
2H), 7.27 (t, 2H, J¼8 Hz), 7.37 (d, 2H, J¼8 Hz). 13C NMR
(100 MHz, CDCl3): d 20.3, 27.6, 41.1, 49.9, 58.4, 115.8,
116.1, 123.0, 123.3, 126.3, 127.5, 127.7, 128.3, 129.6, 130.5,
131.8, 146.5, 150.1, 151.9, 216.1. HRMS (ESI): (MH)þ, found:
341.4284, C24H20O2 requires: 341.4287.
1156, 979, 935, 878, 765, 755, 702 cmꢂ1 1H NMR
.
(400 MHz, CDCl3): d 0.93 (s, 6H), 2.05 (s, 3H), 6.99 (t, 2H,
J¼6.8 Hz), 7.07 (d, 2H, J¼8 Hz), 7.20 (t, 3H, J¼8.4 Hz),
7.31 (m, 6H). 13C NMR (100 MHz, CDCl3): d 21.5, 24.1,
86.9, 116.0, 122.4, 122.6, 127.1, 127.5, 127.6, 129.4, 130.8,
143.7, 151.7, 210.8. HRMS (ESI): (MNa)þ, found:
397.4255, C24H24O4Na requires: 397.4252.
4.3.5. 1,3-Diphenyl-1-(9-phenyl-9H-xanthen-9-yl)-propan-
2-one (1e)
4.3.9. rac-1-Phenyl-1-(9-phenyl-9H-xanthen-9-yl)-propan-
2-one (1i)
White solid, mp 141e143 ꢁC. Rf¼0.69 (EtOAc/hexane
White solid, mp 185e188 ꢁC. Rf¼0.67 (EtOAc/hexane
2:98). IR (KBr): 3076, 3054, 3021, 2884, 1711, 1599, 1572,
1476, 1443, 1347, 1319, 1305, 1281, 1242, 1149, 1122,
2:98). IR (KBr): 3060, 3030, 2884, 1722, 1600, 1573, 1477,
.
1444, 1311, 1280, 1245, 1098, 1037, 753, 701 cmꢂ1 1H
NMR (400 MHz, CDCl3): d 3.46 (d, 1H, J¼14.8 Hz), 3.59
(d, 1H, J¼14.8 Hz), 4.69 (s, 1H), 6.17 (d, 2H, J¼7.2 Hz),
6.57 (d, 1H, J¼8 Hz), 6.69 (dd, 3H, J1¼8 Hz, J2¼15.6 Hz),
6.86 (t, 2H, J¼7.2 Hz), 6.97 (t, 2H, J¼8 Hz), 7.02e7.39 (m,
12H), 7.62 (d, 1H, J¼8 Hz). 13C NMR (100 MHz, CDCl3):
d 50.5, 67.7, 115.3, 115.7, 121.8, 122.8, 126.3, 127.1, 127.6,
127.8, 128.0, 128.3, 128.5, 128.7, 129.4, 129.5, 129.7,
130.0, 131.1, 133.7, 134.4, 146.4, 151.2, 152.9, 204.8.
HRMS (ESI): (MH)þ, found: 467.5857, C34H26O2 requires:
467.5861.
1031, 880, 864, 770, 749, 702 cmꢂ1 1H NMR (400 MHz,
.
CDCl3): d 2.05 (s, 3H), 4.60 (s, 1H), 6.17 (d, 2H,
J¼7.2 Hz), 6.67 (d, 2H, J¼8 Hz), 6.73 (d, 1H, J¼8 Hz),
6.88 (t, 1H, J¼8 Hz), 6.95 (t, 2H, J¼7.6 Hz), 7.05 (m, 2H),
7.18 (m, 2H), 7.28 (m, 5H), 7.64 (d, 1H, J¼8 Hz). 13C
NMR (100 MHz, CDCl3): d 30.9, 52.7, 68.8, 115.0, 115.5,
121.6, 122.6, 123.4, 126.2, 127.4, 127.5, 127.6, 127.8,
128.1, 129.1, 129.8, 130.5, 133.6, 134.2, 146.4, 150.9,
152.7, 205.4. HRMS (ESI): (MH)þ, found: 391.4878,
C28H22O2 requires: 391.4885.
4.3.6. rac-3-(9-Phenyl-9H-xanthen-9-yl)-butan-2-one (1f)
White solid, mp 142e143 ꢁC. Rf¼0.48 (EtOAc/hexane
2:98). IR (KBr): 3071, 3033, 2929, 2870, 1701, 1603, 1571,
1484, 1441, 1363, 1305, 1278, 1245, 1183, 1045, 938, 902,
4.3.10. rac-3-Oxo-2-(9-phenyl-9H-xanthen-9-yl)-butyric
acid ethyl ester (1j)
White solid, mp 125e128 ꢁC. Rf¼0.35 (EtOAc/hexane
2:98). IR (KBr): 3056, 3033, 2992, 2940, 1726, 1717, 1602,
1574, 1481, 1446, 1357, 1308, 1284, 1260, 1217, 1042,
1
871, 761, 717 cmꢂ1. H NMR (400 MHz, CDCl3): d 1.14 (d,
3H, J¼6.8 Hz), 1.53 (s, 3H), 3.80 (q, 1H), 6.72 (dd, 1H,
J¼1.6, 7.6 Hz), 6.78 (dd, 1H, J¼1.6, 8 Hz), 6.98 (m, 2H),
7.06 (m, 1H), 7.14 (m, 3H), 7.31 (m, 5H). 13C NMR
(100 MHz, CDCl3): d 14.6, 31.5, 50.1, 55.2, 116.1, 116.4,
116.7, 122.1, 123.2, 123.3, 124.3, 126.5, 126.6, 127.6,
128.0, 128.2, 128.3, 128.5, 128.6, 129.2, 130.0, 130.2,
1016, 906, 876, 763, 702 cmꢂ1 1H NMR (400 MHz,
.
CDCl3): d 1.08 (t, 3H, J¼7.8 Hz), 1.80 (s, 3H), 3.97 (dq, 2H
J1¼7.2 Hz, J2¼1.2 Hz), 4.61 (s, 1H), 6.86 (d, 1H,
J¼7.6 Hz), 6.92 (q, 2H, J¼8 Hz), 7.01 (d, 1H, J¼8 Hz),
7.10 (d, 2H, J¼8 Hz), 7.21 (m, 3H), 7.28 (t, 2H, J¼6.4 Hz),
7.36 (d, 2H, J¼6.8 Hz). 13C NMR (100 MHz, CDCl3):

V. Kavala et al. / Tetrahedron 64 (2008) 3960e3965
3965
2. (a) Burghardt, T. P.; Ajtai, K. Biophys. Chem. 1996, 60, 119; (b) Yang, Y.;
Escobedo, J. O.; Wong, A.; Schowalter, C. M.; Touchy, M. C.; Jiao, L.;
Crowe, W. E.; Fronczek, R. J. Org. Chem. 2005, 70, 6907; (c) Saki, N.;
Dinc, T.; Akkaya, E. U. Tetrahedron 2006, 62, 2721; (d) Wang, H.; Lu, L.;
Zhu, S.; Li, Y.; Cai, W. Curr. Microbiol. 2006, 52, 1; (e) Gakamsky, D. M.;
Davis, D. M.;Haas, E.; Strominger, J. L.;Pecht, I. Biophys. J. 1999, 76, 1552.
3. (a) Iwasa, S.; Ishima, Y.; Widagdo, H. S.; Aoki, K.; Nishiyama, H.
Tetrahedron Lett. 2004, 45, 2121; (b) Sergeev, A. G.; Artamkina, G. A.;
Beletskaya, I. P. Tetrahedron Lett. 2003, 44, 4719; (c) Kim, D.; Park,
B.-M.; Yun, J. Chem. Commun. 2005, 1755; (d) Saki, N.; Akkaya, E. U.
J. Mol. Catal. A: Chem. 2004, 219, 227.
d 13.8, 31.2, 61.4, 67.8, 115.8, 116.2, 122.4, 122.8, 125.7,
126.4, 127.6, 128.4, 129.6, 130.6, 131.8, 151.2, 151.3,
167.6, 201.2. HRMS (ESI): (MH)þ, found: 385.4281,
C25H20O4 requires: 385.4277.
Acknowledgements
B.K.P. acknowledges the support of this research from DST
(SR/S1/OC-15/2006) and CSIR (01/1946/04/EMR-II), New
Delhi. S.M. acknowledges the financial support from CSIR
and V.K. acknowledges the financial support from the institute.
Thanks are due to CIF IIT Guwahati for NMR spectra, DST
FIST for XRD facility.
4. (a) Jacobs, A.; Nassimbeni, L. R.; Su, H.; Taljaard, B. Org. Biomol. Chem.
2005, 3, 1319; (b) Jacobs, A.; Nassimbeni, L. R.; Taljaard, B. Acta Crys-
tallogr., Sect. C 2004, 60, 668; (c) Kavala, V.; Murru, S.; Patel, B. K.; Das,
G. J. Chem. Crystallogr. 2007, 527.
5. (a) Roy, R. K.; Pagaria, P.; Naik, S.; Kavala, V.; Patel, B. K. J. Phys.
Chem. A 2006, 110, 2181; (b) Roy, R. K.; Usha, V.; Patel, B. K.; Hairo,
K. J. Comput. Chem. 2006, 773; (c) Kavala, V.; Patel, B. K. Eur.
J. Org. Chem. 2005, 441; (d) Naik, S.; Kavala, V.; Gopinath, R.; Patel,
B. K. ARKIVOC 2006, 119; (e) Naik, S.; Gopinath, R.; Goswami, M.;
Patel, B. K. Org. Biomol. Chem. 2004, 1670; (g) Gopinath, R.; Haque,
Sk. J.; Patel, B. K. J. Org. Chem. 2002, 67, 5842; (h) Naik, S.; Gopinath,
R.; Patel, B. K. Tetrahedron Lett. 2001, 42, 7679; (i) Gopinath, R.; Patel,
B. K. Org. Lett. 2000, 2, 4177.
References and notes
1. (a) Mehta, A.; Srivastava, S. K.; Gupta, J. B. Patent no. WO 2004056810,
2004; (b) Birnberg, N. C.; Weng, Q.; Liu, H.; Avruch, J.; Kyriakis, J. Patent
no. WO 2004044219, 2004; (c) Chibale, K.; Visser, M.; von Schalkwyk, D.;
Smith, P. J.; Saravanamuthu, A.; Fairlamb, A. H. Tetrahedron 2003, 59,
2289; (d) Wu, C.-P.; Van Schalkwyk, D. A.; Taylor, D.; Smith, P. J.; Chibale,
K. Int. J. Antimicrob. Agent 2005, 26, 170; (e) Chatterjee, S.; Iqbal, M.;
Kauer, J. C.; Mallamo, J. P.; Senadhi, S.; Mallya, S.; Bozyczko-Coyne,
D.; Siman, R. Bioorg. Med. Chem. Lett. 1996, 6, 1619; (f) Wichmann, J.;
Bleicher, K.; Vieira, E.; Woltering, T.; Knoflach, F.; Mutel, V. Farmaco
2002, 57, 989; (g) Vieira, E.; Huwyler, J.; Jolidon, S.; Knoflach, F.; Mutel,
V.; Wichmann, J. Bioorg. Med. Chem. 2005, 15, 4628; (h) Naya, A.; Sagara,
Y.; Ohwaki, K.; Saeki, T.; Ichasawa, Y.; Naguchi, K.; Ohtake, N. J. Med.
Chem. 2001, 44, 1429; (i) Naya, A.; Ishikawa, M.; Matsuda, K.; Ohwaki,
K.; Saeki, T.; Naguchi, K.; Ohtake, N. Bioorg. Med. Chem. 2003, 11, 875.
6. Kavala, V.; Naik, S.; Patel, B. K. J. Org. Chem. 2005, 70, 4267.
7. (a) Naik, S.; Kavala, V.; Gopinath, R.; Patel, B. K. ARKIVOC 2006, 21; (b)
Singh, C. B.; Murru, S.; Kavala, V.; Patel, B. K. Org. Lett. 2006, 8, 5397;
(c) Murru, S.; Kavala, V.; Singh, C. B.; Patel, B. K. Tetrahedron Lett.
2007, 48, 1007; (d) Singh, C. B.; Murru, S.; Kavala, V.; Patel, B. K.
J. Chem. Res. 2007, 136; (e) Murru, S.; Singh, C. B.; Kavala, V.; Patel,
B. K. Tetrahedron 2008, 64, 1931.
8. (a) Prashad, M.; Lu, Y.; Repiꢀc, O. J. Org. Chem. 2004, 69, 584; (b) Okamoto,
K.; Takeuchi, K.; Kitagawa, T. Adv. Phys. Org. Chem. 1995, 39, 173.
9. Wada, M.; Kirishima, K.; Oki, Y.; Miyamoto, M.; Asahara, M.; Erabi, T.
Bull. Chem. Soc. Jpn. 1999, 72, 779.
10. Allegretti, P. E.; Schiavoni, M. M.; Cortizo, M. S.; Castro, E. A.; Furlong,
J. J. P. Int. J. Mol. Sci. 2004, 5, 294.