An economical noncatalytic approach to the synthesis of congested diaryl ethers and aryl benzyl thioethers through C-C insertion

Article abstract of DOI:10.1055/s-0029-1217804

An efficient one-pot synthesis of diaryl ethers and aryl benzyl thioethers has been delineated through base-induced ring transformation of 6-aryl-4-methylthio-2H-pyran-2-one-3-carbonitriles, methyl 6-aryl-4-methylthio- 2H-pyran-2-one-3-carboxylates and 6-aryl-4-(piperidin-1-yl)-2H-pyran-2-one-3- carbonitriles by either 1-phenoxypropan-2-one, 1,3-diphenoxypropan-2-one or 4-arylthiobutan-2-one, under very mild reaction conditions, in excellent yield. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0029-1217804

LETTER
2265
An Economical Noncatalytic Approach to the Synthesis of Congested Diaryl
Ethers and Aryl Benzyl Thioethers through C–C Insertion
Congested
Di
a
E
thers
r
and
A
ry
h
l
Benzyl
T
h
a
ioethers nullah, Vishnu ji Ram*
Department of Applied Chemistry, Institute of Engineering and Technology, Sitapur Road, Lucknow 226020, India
Fax +91(522)2623405; E-mail: vjiram@yahoo.com
Fax +65 6779 1691; E-mail: farhanullah73@yahoo.com
Received 15 May 2009
ethers. Nucleophilic aromatic substitution under metal-
Abstract: An efficient one-pot synthesis of diaryl ethers and aryl
benzyl thioethers has been delineated through base-induced ring
transformation of 6-aryl-4-methylthio-2H-pyran-2-one-3-carbo-
nitriles, methyl 6-aryl-4-methylthio-2H-pyran-2-one-3-carboxy-
free coupling conditions can also be an important alterna-
tive.18 Recently, diaryl ethers have also been synthesized
under very mild reaction conditions through oxidative
lates and 6-aryl-4-(piperidin-1-yl)-2H-pyran-2-one-3-carbonitriles arylation of phenols with N,N-dialkyl-4-phenylthio-
by either 1-phenoxypropan-2-one, 1,3-diphenoxypropan-2-one or
anilines in the presence of 1,8-bis(diphenylmethyli-
um)naphthalenediyl19 in moderate yield.
4-arylthiobutan-2-one, under very mild reaction conditions, in ex-
cellent yield.
Despite the development of numerous protocols for the
construction of diaryl ethers, mild reaction procedures are
still in high demand. Herein, we report an economical and
efficient synthesis of congested diaryl ethers through
Key words: 6-aryl-4-methylthio-2H-pyran-2-one-3-carbonitriles,
ring transformation, diaryl ethers, 1,3-diphenoxypropan-2-one
base-induced ring transformation of 6-aryl-4-methylthio-
Diaryl ethers and diaryl thioethers are important structural
2H-pyran-2-one-3-carbonitriles (1a, 1b, 1d and 1e), me-
motifs that are present as sub-structures in a wide variety
thyl 6-aryl-4-methylthio-2H-pyran-2-one-3-carboxylates
of natural products, and are employed as ‘building blocks’
(1c, 1f and 1g) and 6-aryl-4-(piperidin-1-yl)-2H-pyran-2-
in organic synthesis, material science, pharmaceuticals
one-3-carbonitriles (1h) by either 1-phenoxypropan-2-
and agrochemicals. These compounds have been isolated
one (2a) or 1,3-diphenoxypropan-2-one (2b), using anhy-
as breakdown products, depsidones1 from lichens,
drous potassium carbonate and powdered potassium
bastadines2 from sponges, combretastatines3 from plants,
hydroxide as a base in N,N-dimethylformamide under stir-
riccardin B4 from mosses and piperazinomycin5 from dif-
ring at room temperature for 2–3 hours. Under analogous
ferent microorganisms. In various natural products, the
conditions, aryl benzyl thioethers have also been prepared
diaryl ether basic structure is present as mono-, di- and re-
by the ring transformation of 1a by 4-arylthiobutan-2-one.
peated units within macrocyclic frame-works,6,7 and is re-
The precursors, 6-aryl-4-methylthio-2H-pyran-2-one-3-
carbonitriles/carboxylates 1 were prepared20 by the reac-
tion of aryl methyl ketone with either methyl 2-cyano-3,3-
dimethylthioacrylate or methyl 2-carbomethoxy-3,3-di-
methylthioacrylate. Amination21 of 1b with piperidine in
boiling ethanol afforded 1h in good yield. 1,3-Diphenoxy-
propan-2-one (2b), which was used to generate the carbon
nucleophile, was synthesized through a sequence of reac-
tions from glycerol as depicted in Scheme 1. Selective ha-
logenation of glycerol followed by coupling with phenol,
afforded 1,3-diphenoxypropan-2-ol.22 Oxidation of the
latter to the corresponding ketone 2b by a range of oxidiz-
ing agents failed; however, ultimately, use of Jones
sponsible for a diverse range of pharmacological
activities8 such as anticancer, anti-inflammatory, anal-
gesic, antiviral, antibacterial and antipyretic actions.9 The
multifarious pharmacological activities and lack of non-
catalytic synthetic approaches led us to develop an effi-
cient and economical route to the construction of highly
congested aryl ethers with mono- and di-ether linkages.
The synthesis of diaryl ethers commonly begins with clas-
sical Ullman ether synthesis10 from Cu(I)-mediated cou-
pling reaction of phenols with aryl halides. However, the
harsh reaction conditions are often incompatible with
many functional groups at higher temperature, thus se-
verely limiting its application in organic synthesis. There-
after, many alternative synthetic strategies have been
developed in order to improve the yields of diaryl ethers
by using either ionic liquid11 or catalysts such as copper-
phenanthroline complexes,12 1,3-diketone,13 amino ac-
ids,14 or glyoxalhydrazone.15 The palladium-catalyzed
coupling, using electron-rich phosphine ligands16 and SN
Ar-based reactions of aryl fluorides17 or metal arene com-
plexes, have also been used for the synthesis of aryl
ii
i
PhO
OPh
PhO
OPh
X
Cl
Cl
O
OH
iii
OH
2b
PhO
OPh
O
2b
SYNLETT 2009, No. 14, pp 2265–2268
Advanced online publication: 07.08.2009
DOI: 10.1055/s-0029-1217804; Art ID: G15509ST
© Georg Thieme Verlag Stuttgart · New York
x
x
.x
x
.2
0
0
9
Scheme 1 Reagents and conditions: (i) phenol, K2CO3, DMF,
135 °C, 8 h, 52%; (ii) (a) Dess–Martin periodinane; (b) Swern oxida-
tion; (c) PCC; (iii) CrO3, H2SO4, 6 h, quantitative.

2266
Farhanullah, V. j. Ram
LETTER
SMe
SH
Me
O
O
CN
Me
i
ii
Me
S
Me
+
Me
Ph
5
S
X
ii
SMe
Me
CN
6
Me
Ph
S
7
Scheme 2 Reagents and conditions: (i) Bi(NO3)3, CH2Cl2, 25 °C, 3 h, 50%; (ii) 1a, KOH, DMF, r.t., 5 h, 52%.
reagent23 gave desired product in quantitative yield. The of the pyran ring together with elimination of carbon
4-phenylthiobutan-2-one (5), used as a carbanion source dioxide and water as depicted in Scheme 3, path A. The
for the ring transformation, was prepared by Bismuth ni- possibility for the formation of 3-methylthio-5-(phen-
trate catalyzed Michael addition of thiophenols on methyl oxymethyl)biphenyl-4-carbonitrile 4 was also envisaged
vinyl ketone (Scheme 2).24
from the reaction of 1a with 2a through Path B, however,
in practice, only 3a was isolated (Scheme 3). The reason
for the exclusive formation of 3a rather than 4a is possibly
due to the combined negative inductive effects of both the
phenoxy and carbonyl groups in the former, which leads
to facile generation of a carbanion at the methylene car-
bon compared to methyl group.
Analysis of the molecular makeup of 6-aryl-4-methylthio-
2H-pyran-2-one-3-carbonitriles/carboxylates 1 revealed
the presence of three electrophilic sites at C-2, C-4, and
C-6, in which the latter was the most electron-deficient
due to both extensive conjugation and to the presence of
an electron-withdrawing CN or CO2Me substituent at the
3-position of the pyran ring. The C-6 position of the pyran Under analogous conditions, reaction of 1 with 1,3-diphen-
ring, being a harder electrophilic centre compared to C-2 oxypropan-2-one (2b) in the presence of potassium car-
and C-4, is preferentially attacked by hard carbanion nu- bonate did not take place but went smoothly when pow-
cleophiles, generated in situ either from 1-phenoxypro- dered potassium hydroxide was used as a base to give 5-
pan-2-one (2a) or 1,3-diphenoxypropan-2-one (2b) in the methylthio-2-phenoxy-3-(phenoxymethyl)biphenyl-4-
presence of powdered K2CO3/KOH. However, while at- carbonitrile/carboxymethyl compounds 3d–g and 3h in
tack at the C-4 center by a carbanion in the initial step will very good yields (Table 1).
lead to the formation of an intermediate substitution prod-
uct which may cyclize to a bicyclic product, in case of C-2
attack there is a possibility for the formation of either a
The aryl thioketone 5, used for the ring transformation of
1 was prepared through Michael addition of 4-methyl-
thiophenol on methyl vinyl ketone. Thus, stirring an
ring-opened or a cyclized product, depending upon the na-
equimolar mixture of 4-(4-methylphenyl)thiobutan-2-one
ture of nucleophile used. In practice, we neither isolated
(5) and 2-pyranone 1a in the presence of powdered potas-
nor characterized such respective products (IR, Mass and
NMR spectroscopy).
Table 1 Formation of Congested Diaryl Ethers and Aryl Benzyl
The progress of the reaction was clearly observed from
evolution of carbon dioxide bubbles. Thus, a mixture of
1a and ketone 2a was stirred with anhydrous potassium
carbonate in N,N-dimethylformamide at room tempera-
ture for 2–3 hours then poured onto crushed ice with vig-
orous stirring followed by neutralization with 10%
aqueous HCl. The resulting precipitate was filtered,
washed with water, dried and purified by silica gel column
chromatography. The isolated compound was identified
as 3-methyl-5-methylthio-2-phenoxybiphenyl-4-carbo-
nitrile (3a; Table 1).
Thioethers 3a–h
1,3 Ar
X
Y
R
Base
Yield
(%)
a
b
c
d
e
f
Ph
SMe
CN
H
H
H
K2CO3 72
K2CO3 74
K2CO3 68
4-BrC6H4 SMe
4-BrC6H4 SMe
CN
CO2Me
CN
Ph
4-BrC6H4 SMe
Ph SMe
4-BrC6H4 SMe
SMe
OPh KOH
OPh KOH
82
86
85
84
82
CN
The initial step in this reaction is possibly the formation of
a Michael adduct by attack of a carbanion generated in
situ from ketone 2 at C-6, with subsequent ring-opening
and recyclization involving the carbonyl function and C-3
CO2Me OPh KOH
CO2Me OPh KOH
g
h
4-BrC6H4 piperidin-1-yl CN
OPh KOH
Synlett 2009, No. 14, 2265–2268 © Thieme Stuttgart · New York

LETTER
Congested Diaryl Ethers and Aryl Benzyl Thioethers
2267
X
protocol provides an economical, noncatalytic approach
to the synthesis of congested unsymmetrical diaryl ethers
and aryl benzyl thioethers under very mild reaction condi-
tions.
Y
PhO
R
+
O
Ar
O
O
2
1
a) R = H
base
b) R = OPh
Acknowledgment
path A
X
2a
O
path B
The authors are thankful to AICTE, New Delhi for financial support
and to the Sophisticated Analytical Instrument Facility, CDRI,
Lucknow, for providing spectroscopic data.
O
O
O
X
X
Y
Y
O
O
OPh
R
References and Notes
Ar
Ar
OPh
(1) (a) Pittayakhajonwut, P.; Dramae, A.; Madla, S.;
Lartpornmatulee, N.; Boonyuen, N.; Tanticharoen, M.
J. Nat. Prod. 2006, 69, 1361. (b) Rukachaisirikul, V.;
Naklue, W.; Phongpaichit, S.; Towatana, N. H.; Maneenoon,
K. Tetrahedron 2006, 62, 8578.
(2) (a) Coll, J. C.; Kearns, P. S.; Rideout, J. A.; Sankar, V.
J. Nat. Prod. 2002, 65, 753. (b) Kotoku, N.; Tsujita, H.;
Hiramatsu, A.; Mori, C.; Koizumi, N.; Kobayashi, M.
Tetrahedron 2005, 61, 7211.
(3) (a) Cirla, A.; Mann, J. Nat. Prod. Rep. 2003, 20, 558.
(b) Hsieh, H. P.; Liou, J. P.; Mahindroo, N. Curr. Pharm.
Des. 2005, 11, 1655.
(4) (a) Kodama, M.; Shiobara, Y.; Sumitomo, H.; Matsumura,
K.; Tsukamoto, M.; Harada, C. J. Org. Chem. 1988, 53, 72.
(b) Nógrádi, M.; Vermes, B.; Kajtár-Peredy, M.
Tetrahedron Lett. 1987, 28, 2899.
O
O
O
O
Y
Y
X
X
OH
OH
OPh
R
R
Ar
Ar
H
H
H
OPh
– CO2
– CO2
Y
X
OH
Y
X
OH
OPh
Ar
OPh
Ar
H
– H2O
– H2O
(5) (a) Nishiyama, S.; Nakamura, K.; Suzuki, Y.; Yamamura, S.
Tetrahedron Lett. 1986, 27, 4481. (b) Beugelmans, R.;
Biogt, A.; Bois-Choussy, M.; Zhu, J. J. Org. Chem. 1996,
61, 771.
(6) (a) Wu, T.-S.; Tsai, Y.-L.; Damu, A. G.; Kuo, P.-C.; Wu,
P.-L. J. Nat. Prod. 2002, 65, 1522. (b) Gao, H.-Y.; Ha,
C.-Y. Synth. Commun. 2006, 36, 3283.
X
X
Y
Y
R
OPh
Ar
Ar
OPh
3
4
(7) Nicolaou, K. C.; Boddy, C. N. C.; Natarajan, S.; Yue, T.-Y.;
Li, H.; Bräse, S.; Ramanjulu, J. M. J. Am. Chem. Soc. 1997,
119, 3421.
Scheme 3 Reagents and conditions: K2CO3, KOH, DMF, r.t., 2–3 h,
68–82%.
(8) (a) Sawyer, J. S. Tetrahedron 2000, 56, 5045. (b) Ley, S.
V.; Thomas, A. W. Angew. Chem. Int. Ed. 2003, 42, 5400.
(c) Frlan, R.; Kikelj, D. Synthesis 2006, 2271. (d) Betson,
M. S.; Clayden, J.; Worrall, C. P.; Peace, S. Angew. Chem.
Int. Ed. 2006, 45, 5803.
sium hydroxide in N,N-dimethylformamide for five hours
provided 3-methylthio-5-methyl-6-(4-methylphenylthio-
methyl)biphenyl-4-carbonitrile (6) after usual workup and
purification by silica gel column chromatography
(Scheme 2). Theoretically, there was also a possibility for
the formation of 3-methylthio-5-[2-(4-methylphenyl-
thio)ethyl]biphenyl-4-carbonitrile (7) but, in practice,
only 6 was isolated.
(9) (a) Crowley, B. M.; Boger, D. L. J. Am. Chem. Soc. 2006,
128, 2885. (b) Reddy, V. L. N.; Ravinder, K.; Srinivasulu,
M.; Goud, T. V.; Reddy, S. M.; Srujankumar, D.; Rao, T. P.;
Murty, U. S.; Venkateswarlu, Y. Chem. Pharm. Bull. 2003,
51, 1081. (c) Quideau, S.; Feldman, K. S.; Appel, H. M.
J. Org. Chem. 1995, 60, 4982. (d) Reddy, A. V.; Ravinder,
K.; Narasimhulu, M.; Sridevi, A.; Satyanarayana, N.;
Kondapi, A. K.; Venkateswarlu, Y. Bioorg. Med. Chem.
2006, 14, 4452. (e) Hagmann, W. K.; Dorn, C. P.;
Frankshun, R. A.; O’Grady, L. A.; Bailey, P. J. J. Med.
Chem. 1986, 29, 1436. (f) In, J.-K.; Lee, M.-S.; Yang, J.-E.;
Kwak, J.-H.; Lee, H.; Boovanahalli, S. K.; Lee, K.; Kim,
S. J.; Moon, S. K.; Lee, S.; Choi, N. S.; Ahn, S. K.; Jung,
J.-K. Bioorg. Med. Chem. Lett. 2007, 17, 1799.
(10) (a) Theil, F. Angew. Chem. Int. Ed. 1999, 38, 2345.
(b) Lindley, J. Tetrahedron 1984, 40, 1433.
The obvious reason for the formation of 6 was due to the
generation of the carbanion at C-3 rather than at C-1 in 5
because of the combined negative inductive effect of both
the arylthio and acetyl groups.
All the synthesized compounds were characterized by
spectroscopic techniques and data of representative com-
pounds are presented in the reference section.25
In summary, the synthesis of aryl ethers and aryl benzyl
thioether (3 and 6) is reported for the first time. The meth-
od uses base-catalyzed ring transformation of suitably
functionalized 2-pyranones with 1-phenoxy-2-propanone,
1,3-diphenoxy-2-propanone, and 4-arylthiobutan-2-one,
through C–C insertion, and gives excellent yields. The
(11) Luo, Y.; Wu, J. X.; Ren, R. X. Synlett 2003, 1734.
(12) Gujadhur, R. K.; Bates, C. G.; Venkataraman, D. Org. Lett.
2001, 3, 4315.
(13) Buck, E.; Song, Z. J.; Tschaen, D.; Dormer, P. G.; Volante,
R. P.; Reider, P. J. Org. Lett. 2002, 4, 1623.
(14) Ma, D.; Cai, Q. Org. Lett. 2003, 5, 3799.
Synlett 2009, No. 14, 2265–2268 © Thieme Stuttgart · New York

2268
Farhanullah, V. j. Ram
LETTER
(15) Liu, Y.-H.; Li, G.; Yang, L.-M. Tetrahedron Lett. 2009, 50,
343.
76.57; H, 5.00; N, 3.31. Found: C, 76.66; H, 5.18; N, 3.42.
Compound 3e: mp 152–154 °C. IR (KBr): 2210 (CN) cm–1;
1H NMR (200 MHz, CDCl3): d = 2.61 (s, 3 H), 5.11 (s, 2 H),
6.56 (d, J = 8.70 Hz, 2 H), 6.82–6.96 (m, 3 H), 7.06–7.09
(m, 2 H), 7.19–7.28 (m, 4 H), 7.36 (d, J = 8.70 Hz, 2 H),
7.65 (d, J = 8.70 Hz, 2 H); MS (FAB): m/z = 503 [M+ + 1];
Anal. Calcd for C27H20BrNO2S: C, 64.55; H, 4.01; N, 2.79.
Found: C, 64.65; H, 4.16; N, 2.90. Compound 3f: mp 154–
156 °C. IR (KBr): 1768 (CO2Me) cm–1; 1H NMR (200 MHz,
CDCl3): d = 2.51 (s, 3 H), 3.83 (s, 3 H), 5.07 (s, 2 H), 6.62
(d, J = 8.80 Hz, 2 H), 6.82–6.96 (m, 4 H), 7.06–7.09 (m,
2 H), 7.19–7.28 (m, 6 H), 7.36–7.39 (m, 2 H); MS (FAB):
m/z = 457 [M+ + 1]; Anal. Calcd for C28H24O4S: C, 73.66; H,
5.30; Found: C, 73.77; H, 5.22. Compound 3g: mp 144–
146 °C. IR (KBr): 1764 (CO2Me) cm–1; 1H NMR (200 MHz,
CDCl3): d = 2.56 (s, 3 H), 3.80 (s, 3 H), 5.13 (s, 2 H), 6.76
(d, J = 7.60 Hz, 2 H), 6.89–6.99 (m, 3 H), 7.02–7.05 (m,
1 H), 7.11–7.16 (m, 2 H), 7.21–7.31 (m, 5 H), 7.47 (d,
J = 7.60 Hz, 2 H); MS (FAB): m/z = 536 [M+ + 1]; Anal.
Calcd for C28H23BrO4S: C, 62.81; H, 4.33. Found: C, 62.77;
H, 4.44. Compound 3h: mp 138–140 °C. IR (KBr): 2210
(CN) cm–1; 1H NMR (200 MHz, CDCl3): d = 1.62–1.64 (m,
2 H), 1.81–1.82 (m, 4 H), 3.20 (t, J = 4.8 Hz, 4 H), 5.09 (s,
2 H), 6.56 (d, J = 9.0 Hz, 2 H), 6.83–6.95 (m, 4 H), 7.01–
7.19 (m, 3 H), 7.21–7.30 (m, 4 H), 7.38–7.41 (m, 2 H); MS
(FAB): m/z = 540 [M+ + 1]; Anal. Calcd for C31H27BrN2O2:
C, 69.02; H, 5.04; N, 5.19. Found: C, 69.18; H, 5.26; N, 5.29.
Synthesis of 3-methylthio-5-methyl-6-(4-methylphenylthio-
ethyl)biphenyl-4-carbonitrile (6): A mixture of 2-pyranone 1
(1 mmol), 4-arylthiobutan-2-one 5 (1.2 mmol) and pow-
dered KOH (1.5 mmol) in anhydrous DMF (8 mL) was
stirred at r.t. for 5 h. The reaction mixture was poured onto
crushed ice with vigorous stirring and neutralized with 10%
HCl. The precipitate obtained was filtered, washed with H2O
and finally purified by silica gel column chromatography to
afford 6 in moderate yield (52%). Mp 90–92 °C. IR (KBr):
2214 (CN) cm–1; 1H NMR (200 MHz, CDCl3): d = 2.31 (s,
3 H), 2.51 (s, 3 H), 2.70 (s, 3 H), 3.94 (s, 2 H), 6.97 (s, 1 H),
7.01–7.11 (m, 4 H), 7.37–7.39 (m, 5 H); MS (FAB): m/z =
376 [M+ + 1]; Anal. Calcd for C23H21NS2: C, 73.56; H, 5.64;
N, 3.73. Found: C, 73.18; H, 5.52; N, 4.06.
(16) (a) Mann, G.; Incarvito, C.; Rheingold, A. L.; Hartwig, J. F.
J. Am. Chem. Soc. 1999, 121, 3224; and references therein.
(b) Aranyos, A.; Old, D. W.; Kiyomori, A.; Wolfe, J. P.;
Sadighi, J. P.; Buchwald, S. L. J. Am. Chem. Soc. 1999, 121,
4369.
(17) Li, F.; Wang, Q.; Ding, Z.; Tao, F. Org. Lett. 2003, 5, 2169.
(18) Saitoh, T.; Ichikawa, J. J. Am. Chem. Soc. 2005, 127, 9696.
(19) (a) Freundlich, J. S.; Yu, M.; Kuo, M.; Tsai, H.-C.;
Valderramos, J.-C.; Karagyozov, L.; Jacobs, W. R. Jr.;
Schiehser, G. A.; Fidock, D. A.; Jacobus, D. P.; Sacchettini,
J. C. Bioorg. Med. Chem. Lett. 2006, 16, 2163. (b) Ueno,
M.; Yonemoto, M.; Hashimoto, M.; Wheatley, A. E. H.;
Naka, H.; Kondo, Y. Chem. Commun. 2007, 2264. (c) Xu,
H.; Chen, Y. Synth. Commun. 2007, 37, 2411.
(20) (a) Tominaga, Y.; Ushirogochi, A.; Matsuda, Y.; Kobayashi,
G. Chem. Pharm. Bull. 1984, 32, 3384. (b) Ram, V. J.;
Verma, M. Indian J. Chem., Sect. B: Org. Chem. Incl. Med.
Chem. 1990, 29, 624.
(21) Ram, V. J.; Nath, M.; Srivastava, P.; Sarkhel, S.; Maulik,
P. R. J. Chem. Soc., Perkin Trans. 1 2000, 3719.
(22) Hori, H.; Nishida, Y.; Ohrui, H.; Meguro, H. J. Org. Chem.
1989, 54, 1356.
(23) Nambu, Y.; Endo, T. Tetrahedron Lett. 1990, 31, 1723.
(24) Srivastava, N.; Banik, B. K. J. Org. Chem. 2003, 68, 2109.
(25) General procedure for the synthesis of 5-methylthio-2-
phenoxy-3-(phenoxymethyl)biphenyl-4-carbonitriles/
carboxylates (3d–h): An equimolar mixture of 1 and 2b and
powdered KOH in DMF was stirred for 2–3 h. During this
period, evolution of carbon dioxide bubbles ceased and
starting materials were consumed completely (reaction
monitored by TLC). The reaction mixture was poured into
ice-cold H2O with vigorous stirring. The precipitate thus
obtained was filtered and purified by silica gel column
chromatography to give the product in 68–86% yield.
Compound 3d: mp 133–135 °C. IR (KBr): 2212 (CN) cm–1;
1H NMR (200 MHz, CDCl3): d = 2.60 (s, 3 H), 5.13 (s, 2 H),
6.59 (d, J = 8.70 Hz, 2 H), 6.83–6.93 (m, 4 H), 7.03–7.08
(m, 2 H), 7.19–7.28 (m, 5 H), 7.36–7.41 (m, 3 H); MS
(FAB): m/z = 424 [M+ + 1]; Anal. Calcd for C27H21NO2S: C,
Synlett 2009, No. 14, 2265–2268 © Thieme Stuttgart · New York