Synthesis of the antibacterial benzoquinone primin and its water-soluble analogue, primin acid

Article abstract of DOI:10.1055/s-0029-1218666

The biologically active natural product, primin and its water-soluble acid analogue, primin acid are prepared in 34% and 25% overall yields, respectively, from a common intermediate using a Grignard reaction and a Johnson-Claisen rearrangement as the key

Full text of DOI:10.1055/s-0029-1218666

PAPER
1141
Synthesis of the Antibacterial Benzoquinone Primin and its Water-Soluble
Analogue, Primin Acid
S
ynthesis of Primi
s
n
a
nd Prim
i
in
A
ci
s
d
h K. Bhattacharya,* Tanpreet Kaur, Krishna N. Ganesh
Division of Organic Chemistry and Combi Chem-Bio Resource Centre, National Chemical Laboratory,
Dr. Homi Bhabha Road, Pune-411 008, India
Fax +91(20)25902629; E-mail: ak.bhattacharya@ncl.res.in
Received 1 December 2009; revised 14 December 2009
Dedicated to Dr. Ram P. Sharma, FASc, on the occasion of his 71st birthday
of primin (1) and primin acid (2) employing a Grignard re-
action and a Johnson–Claisen rearrangement9 as the key
steps.
Abstract: The biologically active natural product, primin and its
water-soluble acid analogue, primin acid are prepared in 34% and
25% overall yields, respectively, from a common intermediate us-
ing a Grignard reaction and a Johnson–Claisen rearrangement as the
key steps.
The retrosyntheses of compounds 1 and 2 are shown in
Scheme 1. Compound 7 was envisaged as a common in-
termediate for the synthesis of 1 and 2. Intermediate 7
could be prepared via a Johnson–Claisen rearrangement
of allylic alcohol 5 followed by reduction.
Key words: 1,4-benzoquinones, primin, primin acid, Johnson–
Claisen rearrangement, antibacterial
During a search for potential anticancer agents from the
Suriname rainforest, Kingston et al.1 isolated primin (2-
methoxy-6-pentyl-1,4-benzoquinone) (1) and several oth-
er benzoquinones from the plant Miconia lepidota DC
(Melastomataceae). Primin (1) (Figure 1) has been report-
ed to occur in various plants including Primula obconica
(primrose)2 and Miconia sp.,3 and has also been isolated
from the broth extract of the endophytic fungus, Botry-
osphaeria mamane PSU-M76.4 Compound 1 demon-
strates antibacterial activity against Staphylococcus
aureus ATCC 25923 and methicillin-resistant S. aureus
SK1 with identical minimum inhibitory concentration
(MIC) values of 8 mg/mL, as well as antiprotozoal, anti-
mycobacterial and anticancer activity.1,5 Primin also ex-
OTBS
OH
MeO
CO2Me
MeO
1
2
11
7
TBSO
OH
OH
MeO
CHO
MeO
3
5
Scheme 1 Retrosyntheses of primin (1) and primin acid (2)
hibits allergenic properties, is a strong sensitizer and can The synthesis of common intermediate 7 commenced
induce contact dermatitis.6
from commercially available ortho-vanillin (3)
(Scheme 2). Thus, protection10 of the phenolic hydroxy
group was accomplished using tert-butyldimethylsilyl
chloride in N,N-dimethylformamide to give compound 4
in 95% yield. Reaction of aldehyde 4 with vinylmagne-
sium bromide, under Grignard conditions,11 furnished al-
lylic alcohol 5 in 92% yield. Next, compound 5 was
subjected to Johnson–Claisen rearrangement9 using tri-
methyl orthoacetate, xylene and a catalytic amount of pro-
panoic acid to furnish ester 6 in 90% yield. Hydrogenation
of the alkene in ester 6 resulted in formation of common
intermediate 7. Reduction of the methyl ester group in 7
with lithium aluminum hydride in tetrahydrofuran fur-
nished alcohol 8 in 91% yield.
O
MeO
R
O
1 R = Me
2 R = CO2H
Figure 1 Structures of primin (1) and primin acid (2)
The literature reports five synthetic approaches to
primin,1,7 and only one for its water-soluble analogue,
primin acid (2).7b In continuation of our research on the
synthesis of antibacterial agents and other bioactive mol-
ecules,8 we were interested in the synthesis of 1 and its
water-soluble analogue 2 due to their diverse biological
activity.1,5 Herein, we report a new and efficient synthesis
The primary hydroxy group of 8 was protected to give to-
sylate 9 which underwent reductive cleavage with lithium
aluminum hydride in tetrahydrofuran to afford compound
10. The tert-butyldimethylsilyl group was removed12 us-
ing lithium hydroxide in N,N-dimethylformamide to fur-
nish alcohol 11. Finally, oxidation of 11 with salcomine
SYNTHESIS 2010, No. 7, pp 1141–1144
Advanced online publication: 05.02.2010
DOI: 10.1055/s-0029-1218666; Art ID: Z26109SS
© Georg Thieme Verlag Stuttgart · New York
x
x
.
x
x
.2
0
1
0
[N,N¢-bis(salicylidene)ethylenediaminocobalt(II)]7
forded the title compound, primin (1) in 81% yield.
af-

1142
A. K. Bhattacharya et al.
PAPER
starting materials were obtained from commercial suppliers and
were used without further purification. THF was distilled over sodi-
um/benzophenone. DMF was distilled over 3 Å molecular sieves.
All reactions were conducted using flame-dried glassware under in-
ert atmospheres. Thin layer chromatography (TLC) was performed
using pre-coated silica gel F254 aluminium sheets, obtained from
Merck, Germany. Chromatography refers to purification by column
chromatography using silica gel (100–200 mesh size; Spectrochem,
India). IR spectra were recorded on a Perkin–Elmer Spectra One
FT-IR spectrophotometer. 1H and 13C NMR spectra were recorded
at 200 MHz and 50 MHz, respectively, on a Bruker AC200 spec-
trometer in CDCl3 using TMS as the internal standard. Chemical
shifts (d) are reported in ppm. Coupling constants (J) are given in
Hz. ESI-MS were obtained using an API-Q-Star Applied Biosys-
tems spectrometer. The characterization data of compounds 11,7a 1,1
127b and 27b were in full agreement with reported data.
OH
OTBS
TBSO
OH
MeO
CHO
MeO
CHO
MeO
a
b
3
4
5
c
OTBS
OTBS
MeO
CO2Me
MeO
CO2Me
d
7
6
e
OTBS
OTBS
MeO
MeO
OTs
OH
CAUTION: Primin (1) is a strong sensitizer and should be handled
with care; contact with skin should be avoided.
f
9
8
2-(tert-Butyldimethylsilyloxy)-3-methoxybenzaldehyde (4)
Imidazole (3.3 g, 49.0 mmol) and TBSCl (7.4 g, 49.0 mmol) were
added to a soln of ortho-vanillin (5.0 g, 32.0 mmol) in anhyd DMF
(10 mL). The reaction was complete in 7 h (TLC) and the precipitate
formed during the reaction was extracted with EtOAc (3 × 50 mL).
The combined organic layer was washed with brine (10 mL), dried
over anhyd Na2SO4 and evaporated to give a crude residue which
was purified by chromatography (hexane–EtOAc, 8:2) to afford
product 4.
g
OH
OTBS
MeO
MeO
h
i
1
11
10
Scheme 2 Reagents and conditions: (a) TBSCl, DMF, 95%; (b)
vinylmagnesium bromide, THF, 92%; (c) MeC(OMe)3, xylene, pro-
panoic acid, 90%; (d) H2, Pd/C (10%), MeOH, 94%; (e) LAH, THF,
91%; (f) TsCl, py, 93%; (g) LAH, THF, 95%; (h) LiOH, DMF, 80%;
(i) N,N¢-bis(salicylidene)ethylenediaminocobalt(II), DMF, 81%.
Colorless oil; yield: 8.3 g (95%); Rf = 0.66 (hexane–EtOAc, 7:3).
IR (CHCl3): 3034, 2957, 1584, 1481, 1216, 1071 cm–1.
1H NMR (CDCl3): d = 10.30 (s, 1 H), 7.16 (dd, J = 8.0, 8.0 Hz, 1 H),
6.86–6.70 (m, 2 H), 3.61 (s, 3 H), 0.79 (s, 9 H), 0.00 (s, 6 H).
13C NMR (CDCl3): d = 190.3, 150.8, 149.2, 127.9, 121.2, 119.1,
Cleavage of the tert-butyldimethylsilyl group and hydrol-
ysis of the methyl ester of the key intermediate 7 resulted
in the formation of acid 12. Subsequent oxidation using
the same conditions7 as those employed for the synthesis
of 1 afforded the water-soluble analogue, primin acid (2)
in 71% yield (Scheme 3).
116.9, 55.1, 25.9, 19.0, –4.1.
ESI-MS: m/z = 267 [M + H]+, 289 [M + Na]+, 305 [M + K]+.
Anal. Calcd for C14H22O3Si: C, 63.12; H, 8.32. Found: C, 63.20; H,
8.40.
1-[2-(tert-Butyldimethylsilyloxy)-3-methoxyphenyl]prop-2-en-
1-ol (5)
OH
Compound 4 (3.9 g, 15.0 mmol) was dissolved in anhyd THF (10
mL) and cooled using an ice-bath. Vinylmagnesium bromide (15
mL, 15.0 mmol, 1.0 M in THF) was added over a period of 10 min
and stirring was continued at 0 °C for 5 h. After completion of the
reaction (TLC), aq NH4Cl soln (2 mL) was added, the reaction mix-
ture was diluted with H2O (50 mL) and the product was extracted
with EtOAc (3 × 50 mL). The organic layer was washed with brine
(10 mL), dried over anhyd Na2SO4, and evaporated to furnish a
crude residue which was purified by chromatography (hexane–
EtOAc, 7:3) to give allylic alcohol 5.
MeO
CO2H
a
b
2
7
12
Scheme 3 Reagents and conditions: (a) KOH, MeOH–H2O (3:1),
55%; (b) N,N¢-bis(salicylidene)ethylenediaminocobalt(II), DMF,
71%.
In conclusion, the antibacterial benzoquinones, primin (1)
and its water-soluble analogue, primin acid (2), have been
prepared in 34% and 25% overall yields, respectively,
starting from ortho-vanillin using a Grignard reaction and
a Johnson–Claisen rearrangement as the key steps. The re-
sults described herein constitute a short, efficient and high
yielding synthetic route to compounds 1 and 2 which
should enable further investigation of their biological ac-
tivity.
Colorless oil; yield: 4.05 g (92%); Rf = 0.52 (hexane–EtOAc, 7:3).
IR (CHCl3): 3455, 3018, 2931, 1735, 1459, 1217, 1071 cm–1.
1H NMR (CDCl3): d = 6.98–6.95 (m, 2 H), 6.83–6.81 (m, 1 H),
6.22–6.06 (m, 1 H), 5.71 (t, J = 4.3 Hz, 1 H), 5.44–5.21 (m, 2 H),
3.84 (s, 3 H), 1.05 (s, 9 H), 0.25 (s, 6 H).
13C NMR (CDCl3): d = 149.7, 142.2, 139.4, 133.7, 121.3, 119.0,
114.4, 110.7, 69.0, 54.8, 26.2, 19.0, –3.7.
ESI-MS: m/z = 295 [M + H]+, 317 [M + Na]+, 333 [M + K]+.
Anal. Calcd for C16H26O3Si: C, 65.26; H, 8.90. Found: C, 65.36; H,
8.98.
Melting points were determined in open capillaries using a Büchi B-
5400 melting point apparatus and are uncorrected. Reagents and
Synthesis 2010, No. 7, 1141–1144 © Thieme Stuttgart · New York

PAPER
Synthesis of Primin and Primin Acid
1143
Methyl (4E)-5-[2-(tert-Butyldimethylsilyloxy)-3-methoxyphe-
nyl]pent-4-enoate (6)
5-[2-(tert-Butyldimethylsilyloxy)-3-methoxyphenyl]pentyl 4-
Methylbenzenesulfonate (9)
Compound 5 (4.0 g, 13.6 mmol) in xylene (5 mL) was treated with
trimethyl orthoacetate (9.79 g, 10.2 mL, 8.1 mmol) and propanoic
acid (40 mL), and the resulting mixture was heated at 140 °C for 6
h. After completion of the reaction, the xylene was evaporated un-
der reduced pressure. The crude residue was purified by chromatog-
raphy (hexane–EtOAc, 8:2) to give pure product 6.
Compound 8 (3.0 g, 9.2 mmol) in anhyd CH2Cl2 (10 mL) was treat-
ed with Et3N (1.0 mL), TsCl (1.74 g, 9.2 mmol) and DMAP (cat.)
and the resulting mixture stirred at r.t. for 2 h. After completion of
the reaction (TLC), the reaction mixture was quenched with brine
(10 mL) and extracted with CH2Cl2 (3 × 50 mL). The combined or-
ganic layer was dried over anhyd Na2SO4 and evaporated to give a
crude residue which was purified by chromatography (hexane–
EtOAc, 9:1) to furnish product 9.
Colorless oil; yield: 4.28 g (90%); Rf = 0.60 (hexane–EtOAc, 7:3).
IR (CHCl3): 3021, 2955, 1738, 1480, 1252, 1086 cm–1.
1H NMR (CDCl3): d = 7.32–6.75 (m, 4 H), 6.26–6.13 (m, 1 H), 3.82
(s, 3 H), 3.75 (s, 3 H), 2.75–2.34 (m, 4 H), 1.15 (s, 9 H), 0.28 (s, 6
H).
13C NMR (CDCl3): d = 173.3, 150.6, 142.1, 129.5, 128.3, 126.4,
121.0, 118.0, 110.1, 54.8, 51.5, 33.8, 28.7, 26.1, 18.9, –4.0.
ESI-MS: m/z = 351 [M + H]+, 373 [M + Na]+, 389 [M + K]+.
Colorless oil; yield: 4.11 g (93%); Rf = 0.50 (hexane–EtOAc, 7:3).
IR (CHCl3): 3013, 2920, 1720, 1432, 1389, 1208, 1065 cm–1.
1H NMR (CDCl3): d = 7.71 (d, J = 8.0 Hz, 2 H), 7.60 (d, J = 8.0 Hz,
2 H), 6.63–6.51 (m, 3 H), 3.83 (t, J = 6.3 Hz, 2 H), 3.57 (s, 3 H),
2.39 (t, J = 6.9 Hz, 2 H), 2.27 (s, 3 H), 1.47–1.19 (m, 6 H), 0.81 (s,
9 H), 0.00 (s, 6 H).
13C NMR (CDCl3): d = 149.9, 147.0, 144.8, 142.7, 141.6, 133.4,
130.4, 127.0, 121.9, 120.7, 109.2, 70.7, 54.7, 30.3, 29.4, 28.8, 26.2,
25.3, 21.8, 18.9, –3.7.
Anal. Calcd for C19H30O4Si: C, 65.10; H, 8.63. Found: C, 65.20; H,
8.72.
ESI-MS: m/z = 479 [M + H]+, 501 [M + Na]+, 517 [M + K]+.
Methyl 5-[2-(tert-Butyldimethylsilyloxy)-3-methoxyphe-
nyl]pentanoate (7)
Anal. Calcd for C25H38O5SSi: C, 62.72; H, 8.00. Found: C, 62.67;
H, 8.12.
To compound 6 (4.5 g, 12.8 mmol) in anhyd MeOH (10 mL) was
added 10% Pd/C (0.1 g) and the heterogeneous soln was stirred vig-
orously for 12 h under a H2 atm. After completion of the reaction
(TLC), the mixture was filtered over Celite. The filtrate was evapo-
rated and the crude product was purified by chromatography (hex-
ane–EtOAc, 8:2) to furnish pure ester 7.
tert-Butyl(2-methoxy-6-pentylphenoxy)dimethylsilane (10)
Compound 9 (4.0 g, 8.3 mmol) was dissolved in anhyd THF (10
mL) and cooled in ice-bath. LAH (0.3 g, 8.3 mmol) was added slow-
ly and the reaction mixture stirred at r.t. for 4 h under an Ar atm. Af-
ter completion of the reaction (TLC), the mixture was cooled to 0–
5 °C and quenched with 1 N NaOH (10 mL). The resulting white
precipitate was filtered through Celite, the filtrate dried over anhyd
Na2SO4 and evaporated to give a crude residue which was purified
by chromatography (hexane–EtOAc, 9:1) to furnish product 10.
Colorless oil; yield: 4.24 g (94%); Rf = 0.51 (hexane–EtOAc, 7:3).
IR (CHCl3): 3033, 2937, 1735, 1475, 1234, 1088 cm–1.
1H NMR (CDCl3): d = 6.64–6.54 (m, 3 H), 3.58 (s, 3 H), 3.47 (s, 3
H), 2.46 (t, J = 7.6 Hz, 2 H), 2.14 (t, J = 7.1 Hz, 2 H), 1.55–1.44 (m,
4 H), 0.82 (s, 9 H), 0.00 (s, 6 H).
13C NMR (CDCl3): d = 174.2, 149.9, 142.7, 133.4, 121.8, 120.6,
109.1, 54.7, 51.5, 34.1, 30.2, 29.6, 26.2, 24.9, 18.9, –3.8.
ESI-MS: m/z = 353 [M + H]+, 375 [M + Na]+, 391 [M + K]+.
Colorless oil; yield: 2.4 g (95%); Rf = 0.83 (hexane–EtOAc, 7:3).
IR (CHCl3): 3019, 2839, 1585, 1486, 1261, 1099 cm–1.
1H NMR (CDCl3): d = 6.94–6.74 (m, 2 H), 3.84 (s, 3 H), 2.68 (t,
J = 7.8 Hz, 3 H), 1.65 (t, J = 7.3 Hz, 1 H), 1.42 (t, J = 7.4 Hz, 3 H),
1.08 (s, 9 H), 0.96 (t, J = 6.9 Hz, 3 H), 0.25 (s, 6 H).
13C NMR (CDCl3): d = 149.9, 142.7, 134.3, 129.9, 121.9, 120.5,
108.9, 32.0, 30.6, 30.0, 26.2, 22.7, 19.0, 14.1, –3.4.
ESI-MS: m/z = 309 [M + H]+, 331 [M + Na]+, 347 [M + K]+.
Anal. Calcd for C19H32O4Si: C, 64.73; H, 9.15. Found: C, 64.81; H,
9.22.
5-[2-(tert-Butyldimethylsilyloxy)-3-methoxyphenyl]pentan-1-ol
(8)
Compound 7 (4.0 g, 11.0 mmol) was dissolved in anhyd THF (10
mL) and the soln was cooled using an ice-bath. LAH (0.4 g, 11.0
mmol) was added slowly and the mixture stirred at r.t. for 4 h under
an Ar atm. After completion of the reaction (TLC), the mixture was
cooled to 0–5 °C and quenched with 1 N NaOH (10 mL). The re-
sulting white precipitate was filtered through Celite and the filtrate
was dried over anhyd Na2SO4 and evaporated. The crude residue
was purified by chromatography (hexane–EtOAc, 7:3) to give prod-
uct 8.
Anal. Calcd for C18H32O2Si: C, 70.07; H, 10.45. Found: C, 70.18;
H, 10.58.
2-Methoxy-6-pentylphenol (11)
Compound 10 (1.0 g, 3.2 mmol) was dissolved in anhyd DMF (2
mL) and the soln was cooled in an ice-bath. LiOH (220 mg, 9.6
mmol) was added slowly and the mixture stirred at r.t. for 4 h under
an Ar atm. After completion (TLC), the reaction mixture was ex-
tracted with EtOAc (3 × 20 mL). The combined organic layer was
washed with brine (20 mL), dried over anhyd Na2SO4 and evaporat-
ed to give a crude residue. Purification by chromatography (hex-
ane–EtOAc, 7:3) gave phenol 11 (0.5 g, 80%) as a colorless viscous
oil.7a
Colorless viscous oil; yield: 3.35 g (91%); Rf = 0.31 (hexane–
EtOAc, 7:3).
IR (CHCl3): 2953, 2930, 1720, 1465, 1250, 1082 cm–1.
1H NMR (CDCl3): d = 6.68–6.48 (m, 3 H), 3.58 (s, 3 H), 3.46 (t,
J = 6.4 Hz, 2 H), 2.45 (t, J = 7.3 Hz, 2 H), 1.43–1.13 (m, 6 H), 0.82
(s, 9 H), 0.00 (s, 6 H).
13C NMR (CDCl3): d = 149.9, 142.7, 133.9, 121.9, 120.6, 109.0,
62.9, 54.7, 32.8, 30.0, 29.1, 26.2, 25.8, 18.9, –3.8.
2-Methoxy-6-pentyl-1,4-benzoquinone (Primin) (1)
In a flame-dried flask purged with O2, phenol 11 (388 mg, 2 mmol)
was dissolved in anhyd DMF (3 mL), salcomine (64 mg, 0.2 mmol)
was added, and the reaction mixture was stirred vigorously for 6 h
(TLC). The reaction mixture was extracted with EtOAc (3 × 50 mL)
and the combined organic layer washed with brine (10 mL), dried
over anhyd Na2SO4 and then evaporated to give a crude residue. Pu-
rification by chromatography (hexane–EtOAc, 6:4) gave primin (1)
ESI-MS: m/z = 325 [M + H]+, 347 [M + Na]+, 363 [M + K]+.
Anal. Calcd for C18H32O3Si: C, 66.62; H, 9.94. Found: C, 66.73; H,
9.88.
Synthesis 2010, No. 7, 1141–1144 © Thieme Stuttgart · New York

1144
A. K. Bhattacharya et al.
PAPER
as a yellow solid; yield: 336 mg (81%); mp 61–62 °C (Lit.7a mp 62–
63 °C).
(3) (a) Marini-Bettolo, G. B.; Monache, F. D.; da Lima, O. G.;
Coelho, S. B. Gazz. Chim. Ital. 1971, 101, 41. (b) Bernays,
E.; Lupi, A.; Bettolo, R. M.; Mastrofrancesco, C.;
Tagliatesta, P. Experientia 1984, 40, 1010.
(4) Pongcharoen, W.; Rukachaisirikul, V.; Phongpaichit, S.;
Sakayaroj, J. Chem. Pharm. Bull. 2007, 55, 1404.
(5) Tasdemir, D.; Brun, R.; Yardley, V.; Franzblau, S. G.;
Rüedi, P. Chem. Biodivers. 2006, 3, 1230; and references
cited therein.
(6) (a) Carlsen, B. C.; Menné, T.; Johansen, J. D. Contact
Dermatitis 2008, 59, 96. (b) Bonamonte, D.; Filotico, R.;
Mastrandrea, V.; Foti, C.; Angelini, G. Contact Dermatitis
2008, 59, 174. (c) Fortina, A. B.; Piaserico, S.; Larese, F.;
Recchia, G. P.; Corradin, M. T.; Gennaro, F.; Carrabba, E.;
Peserico, A. Contact Dermatitis 2001, 44, 283.
(7) (a) Bieber, L. W.; Chiappeta, A. D. A.; Souza, M. A. D. M.;
Generino, M.; Neto, P. R. J. Nat. Prod. 1990, 53, 706.
(b) Mabic, S.; Vaysse, L.; Benezra, C.; Lepoittevin, J.-P.
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M.; Moody, C. J. J. Org. Chem. 2005, 70, 4414. (d) Jacob,
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51, 1681. (b) Bhattacharya, A. K.; Jain, D. C.; Sharma, R. P.;
Roy, R.; McPhail, A. T. Tetrahedron 1997, 53, 14975.
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Chem. 2005, 13, 6521.
5-(2-Hydroxy-3-methoxyphenyl)pentanoic Acid (12)
Ester 7 (704 mg, 2 mmol) was dissolved in 5% KOH in MeOH–H2O
(12 mL, 3:1) and the resulting soln heated at reflux for 3 h under an
N2 atm (TLC). The reaction mixture was acidified with 1 N HCl (10
mL) and then extracted with EtOAc (3 × 20 mL). The crude residue
was purified by chromatography (hexane–EtOAc, 6:4) to give acid
12 as a white solid; yield: 246 mg (55%); mp 124–125 °C (Lit.7b mp
125–126 °C).
5-(5-Methoxy-3,6-dioxocyclohexa-1,4-dien-1-yl)pentanoic Acid
(Primin Acid) (2)
In a flame-dried flask purged with O2, phenol 12 (224 mg, 1 mmol)
was dissolved in anhyd DMF (3 mL), salcomine (32 mg, 0.1 mmol)
was added, and the reaction mixture was stirred vigorously for 7 h
(TLC). The reaction mixture was extracted with EtOAc (3 × 50 mL)
and the combined organic layer washed with brine (5 mL), dried
over anhyd Na2SO4 and evaporated to give a crude residue. Purifi-
cation by chromatography (hexane–EtOAc, 4:6) gave primin acid
(2) as a yellow solid; yield: 168 mg (71%); mp 95–97 °C (Lit.7b mp
98 °C).
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.
Acknowledgment
The authors are grateful to Dr. Ganesh Pandey, FNA, Head,
Division of Organic Chemistry for support and encouragement.
T.K. is grateful to the Council of Scientific and Industrial Research,
New Delhi, India for the award of a Senior Research Fellowship.
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Synthesis 2010, No. 7, 1141–1144 © Thieme Stuttgart · New York