'On water' synthesis of 2,4-diaryl-2,3-dihydro-1,5-benzothiazepines catalysed by sodium dodecyl sulfate (SDS)

Article abstract of DOI:10.1016/j.tetlet.2008.04.146

An efficient synthesis of 1,3-diaryl-2,3-dihydro-1,5-benzothiazepines has been developed by the reaction of various 1,3-diaryl-2-propenones with 2-aminothiophenol in water under neutral conditions catalysed by SDS. Excellent chemoselectivity was observed for substrates possessing halogen atoms or nitro/alkoxy/thioalkyl groups which did not undergo competitive aromatic nucleophilic substitution of the halogen atoms or the nitro group, reduction of the nitro or the α,β-unsaturated carbonyl group, or dealkylation of the alkoxy/thioalkoxy groups.

Full text of DOI:10.1016/j.tetlet.2008.04.146

Tetrahedron Letters 49 (2008) 4269–4271
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Tetrahedron Letters
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‘On water’ synthesis of 2,4-diaryl-2,3-dihydro-1,5-benzothiazepines
catalysed by sodium dodecyl sulfate (SDS)
*
Gaurav Sharma, Raj Kumar, Asit K. Chakraborti
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar 160 062, Punjab, India
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient synthesis of 1,3-diaryl-2,3-dihydro-1,5-benzothiazepines has been developed by the reaction
of various 1,3-diaryl-2-propenones with 2-aminothiophenol in water under neutral conditions catalysed
by SDS. Excellent chemoselectivity was observed for substrates possessing halogen atoms or nitro/
alkoxy/thioalkyl groups which did not undergo competitive aromatic nucleophilic substitution of the
halogen atoms or the nitro group, reduction of the nitro or the a,b-unsaturated carbonyl group, or
dealkylation of the alkoxy/thioalkoxy groups.
Received 3 February 2008
Revised 15 April 2008
Accepted 26 April 2008
Available online 1 May 2008
Keywords:
Ó 2008 Elsevier Ltd. All rights reserved.
1,3-Diarylpropenones
2-Aminothiophenol
1,3-Diaryl-2,3-dihydro-1,5-
benzothiazepines
SDS
Water
Catalysis
The broad spectrum of biological activity1 of compounds bear-
ing the 1,5-benzothiazepine moiety has stimulated interest in
developing new synthetic protocols for their synthesis (Scheme
1).2,3 There remains the necessity to develop a more effective and
convenient synthetic procedure as the reported methods have
one or more disadvantages such as the use of a high boiling solvent
(e.g., DMF) that is difficult to recover, excess amounts of acid or
base, special apparatus, corrosive (e.g., HCl gas, TFA) and hazardous
(e.g., pyridine, piperidine, halogenated hydrocarbon) reagents/sol-
vents and special efforts to prepare the catalysts and adsorb the
reactants onto a solid support.
be used in catalytic amounts and water as solvent as an alternative
to volatile organic solvents. Water as a reaction medium has
gained importance in the development of sustainable chemistry.5
In continuation of our efforts in developing ‘On Water’ synthetic
methodologies6, we report a convenient synthesis of 1,5-benzo-
thiazepines in water.
The commonly adopted strategy for the synthesis of benzo-
thiazepines involves cyclocondensation of 1,3-diarylpropenones
with 2-aminothiophenol (Scheme 1). Our initial efforts on the reac-
tion of 1,3-diphenylpropenone (1) with 2-aminothiophenol (2)
under neat conditions at 110 °C (oil-bath) for 12 h did not produce
any significant amount of 1,3-diphenyl-2,3-dihydro-1,5-benzo-
thiazepine (3). When the reaction was carried out in water under
reflux (oil-bath temperature 110 °C) for 12 h, 3 was formed in
15% yield. Recently, it has been demonstrated that the yields in
carrying out the reaction in aqueous medium were superior in
brine than those in water.7 When we used brine, benzothiazepine
3 was obtained in 18% yield. We realised that the presence of the
aryl rings attribute hydrophobic character to 1 and in a biphasic
system the interactions required for the reaction to occur are not
attained. Hence, we thought that the use of a surface-active agent
as a catalyst/additive may be beneficial as it would assemble with
the reactants through hydrophobic interactions excluding the
water molecules from the organic phase forming micelles.8 We
The increasing concern about the tight legislation on the main-
tenance of greenness in synthetic pathways/processes4 led us to
develop a method using a reagent that is less hazardous and can
H N
2
O
SH
+
N
S
1
2
1
2
R
R
R
R
Scheme 1. Synthesis of 2,3-dihydro-1,5-benzothiazepines.
were happy to note that treatment of 1 (1 mmol) with 2
(1.1 mmol) in water (5 mL) at 110 °C (oil-bath) for 12 h in the
presence of SDS (1 mmol) afforded 3 in 65% yield. The use of 50,
10 and 5 mol % of SDS resulted in the formation of 3 in 65%, 65%
* Corresponding author. Tel.: +91 172 2214683; fax: +91 172 2214692.
E-mail address: akchakraborti@niper.ac.in (A. K. Chakraborti).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.04.146

4270
G. Sharma et al. / Tetrahedron Letters 49 (2008) 4269–4271
and 40% yields, respectively, under similar conditions indicating
that a 10 mol % amount of SDS is the critical amount required for
the cyclocondensation. The use of brine as the reaction medium
instead of water afforded comparable yields in the presence of
SDS (10 mol %). The use of water as the reaction medium was
found to be necessary as the treatment of 1 with 2 in the presence
of SDS (10 mol %) at 110 °C (oil-bath) for 12 h under neat
conditions afforded 3 in only 20% yield.
2-Aminothiophenol 2 was added followed by SDS (10 mol %), and
the mixture was heated under reflux (oil-bath temp 110 °C). When
the reactants and SDS were added together, a solid formed which
settled at the bottom of the flask resulting in lower yields due to
incomplete consumption of the starting materials.
In conclusion, we have described a convenient synthesis of 1,3-
diaryl-2,3-dihydro-1,5-benzothiazepines by the reaction of 1,3-
diaryl-2-propenones with 2-aminothiophenol in water catalysed
by SDS.17 The substantial rate acceleration in carrying out the reac-
tion of insoluble substrates in aqueous medium makes this proto-
col an ‘on water’18 synthesis. The advantages are the use of a cheap,
easy to handle and commercially available catalyst and water as
the reaction medium in place of harmful volatile organic solvents.
To establish the generality of this method, we investigated the
cyclocondensation of various substituted 1,3-diarylpropenones
with 2. The starting 1,3-diarylpropenones were prepared by the
Claisen–Schmidt condensation between various substituted aryl
methyl ketones with aryl aldehydes following the LiOHÁH2O
catalysed dual activation procedure.9 The reaction of various 1,3-
diarylpropenones with 2 afforded the corresponding 1,3-diaryl-
2,3-dihydro-1,5-benzothiazepines in 61–79% yields (Table 1). The
reaction was compatible with various electron-donating (Me,
OMe and SMe) and electron-withdrawing (Br, Cl, F, NO2 and
SO2Me) substituents as well as heteroaryl rings. Substrates with
halogen atoms10 (Table 1, entries 2–6, 10, 12 and 18–20) and
NO2groups11 (Table 1, entries 7–9 and 14) did not undergo aro-
matic nucleophilic substitution. The NO212 and the a,b-unsaturated
carbonyl13 groups were not reduced although thiols possess single
electron transfer properties.14 For substrates with aryl alkyl ether/
thioether (Table 1, entries 11–20) groups, no O/S-dealkylation took
place.15,16 The best results were obtained when the reactions were
carried out as follows: the 1,3-diarylpropenone in water was
heated under reflux (oil-bath temp 110 °C) under magnetic stirring
until it formed a melt and mixed with water as tiny droplets.
Acknowledgement
The authors thank OPCW, Hague, The Netherlands for financial
support.
References and notes
1. Anticonvulsant: (a) Sarro, G. D.; Chimirri, A.; Sarro, A. D.; Gitto, R.; Grasso, S.;
Zappalá, M. Eur. J. Med. Chem. 1995, 30, 925–929; Ca+2 channel antagonist: (b)
Kurokawa, J.; Adachi-Akahane, S.; Nagao, T. Eur. J. Pharmacol. 1997, 325, 229–
232; Anti-HIV: (c) Grandolini, G.; Perioli, L.; Ambrogi, V. Eur. J. Med. Chem.
1999, 34, 701–709; Squalene synthetase inhibitor: (d) Yang, X.; Buzon, L.;
Hamanaka, E.; Liu, K. K.-C. Tetrahedron: Asymmetry 2000, 11, 4447–4451 and
the references cited therein; V2 Arginine vasopressin receptor antagonist: (e)
Urbanski, M. J.; Chen, R. H.; Demarest, K. T.; Gunnet, J.; Look, R.; Ericson, E.;
Murray, W. V.; Rybczynski, P. J.; Zhang, X. Bioorg. Med. Chem. Lett. 2003, 13,
4031–4034; HIV-1 reverse transcriptase inhibitor: (f) Santo, R. D.; Costi, R. IL
Farmaco 2005, 60, 385–392.
Table 1
2. Piperidine (1 mL/mmol) in PhMe or pyridine (15 mL/mmol) under reflux: (a)
Pant, S.; Sharma, A.; Sharma, S. K.; Pant, U. C.; Goel, A. K. Indian J. Chem. 1996,
35B, 794–796; (b) Upreti, M.; Pant, S.; Dandia, A.; Pant, U. C. Indian J. Chem.
1997, 36B, 1181–1184; EtOH–HCl under reflux: (c) Pant, S.; Singhal, B.; Upreti,
M.; Pant, U. Molecules 1998, 3, 159–163; HOAc in DMF or EtOH at 60 °C for
17 h: (d) Micheli, F.; Degiorgis, F.; Feriani, A.; Paio, A.; Pozzan, A.; Zarantonello,
P.; Seneci, P. J. Comb. Chem. 2001, 3, 224–228; HOAc or TFA (1 mL/mmol) in
EtOH or PhMe under reflux: (e) Lévai, A. Heterocycl. Commun. 2002, 8, 375–
380; (f) Lévai, A. Heterocycl. Commun. 2002, 8, 227–232; (g) Lévai, A. J.
Heterocycl. Chem. 2004, 41, 399–403; HOAc (3 mL/mmol) in DMF under
microwave irradiation: (h) Patel, V. M.; Desai, K. R. Indian J. Chem. 2004, B,
199–201; Inorganic supports (2 g/mmol) at 80 °C: (i) Kodomari, M.; Noguchi,
T.; Aoyama, T. Synth. Commun. 2004, 34, 1783–1790; Mg(ClO4)2 in DCE under
reflux: (j) Khatik, G. L.; Kumar, R.; Chakraborti, A. K. Synthesis 2007, 541–546;
HClO4-SiO2 in MeOH under reflux: (k) Khatik, G. L.; Sharma, G.; Kumar, R.;
Chakraborti, A. K. Tetrahedron 2007, 63, 1200–1210.
Synthesis of 2,3-dihydro-1,5-benzothiazepinesa
Entry
Substrate
Time (h)
Yieldb,c (%)
O
R1
R2
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
R1 = R2 = H
12
10
12
12
12
12
10
16
16
8
12
12
12
10
10
8
65
72
76
79
75
76
71
72
72
64
65
74
61
66
65
71
73
68
64
68
62
R1 = H; R2 = 4-Cl
R1 = 4-Cl; R2 = H
R1 = H; R2 = 4-F
R1 = 4-F; R2 = H
R1 = 4-Br; R2 = H
R1 = 4-NO2; R2 = H
R1 = H; R2 = 4-NO2
R1 = H; R2 = 2-NO2
R1 = 4-Cl; R2 = 2-F
R1 = H; R2 = 4-OMe
R1 = 4-Cl; R2 = 4-OMe
R1 = 4-Me; R2 = 4-OMe
R1 = 4-NO2; R2 = 4-OMe
R1 = H; R2 = 4-SMe
R1 = 4-SMe; R2 = 4-Me
R1 = 4-CF3; R2 = 4-SMe
R1 = 4-Cl; R2 = 4-SMe
R1 = 4-SMe; R2 = 4-Cl
R1 = 4-SMe; R2 = 4-F
R1 = 4-CF3; R2 = 4-SO2Me
O
3. For a review see: Lévai, A. J. Heterocycl. Chem. 2000, 37, 199–214 and the
references cited therein.
4. Tundo, P.; Anastas, P.; Black, D. S.; Breen, J.; Collins, T.; Memoli, S.; Miyamoto, J.;
Polyakoff, M.; Tumas, W. Pure Appl. Chem. 2000, 72, 1207–1228.
5. (a) Otto, S.; Engberts, J. B. F. N. Pure Appl. Chem. 2000, 72, 1365–1372; (b) Ribe,
S.; Wipf, P. Chem. Commun. 2001, 299–307; (c) Engberts, J. B. F. N.; Blandamer,
M. J. Chem. Commun. 2001, 1701–1708; (d) Otto, S.; Engberts, J. B. F. N. Org.
Biomol. Chem. 2003, 1, 2809–2820; (e) Li, C.-J. Chem. Rev. 2005, 105, 3095–
3165; (f) Narayan, S.; Muldoon, J.; Finn, M. G.; Fokin, V. V.; Kolb, H. C.;
Sharpless, K. B. Angew. Chem., Int. Ed 2005, 44, 3275–3279; (g) Li, C.-J.; Chen, L.
Chem. Soc. Rev. 2006, 35, 68–82; (h) Lindström, U. M.; Andersson, F. Angew.
Chem., Int. Ed 2006, 45, 548–551; (i) Hailes, H. C. Org. Proc. Res. Dev. 2007, 11,
114–120.
6
12
10
6
6. (a) Khatik, G. L.; Kumar, R.; Chakraborti, A. K. Org. Lett. 2006, 8, 2433–2436; (b)
Chankeshwara, S. V.; Chakraborti, A. K. Org. Lett. 2006, 8, 3259–3262; (c)
Chakraborti, A. K.; Rudrawar, S.; Jadhav, K. B.; Kaur, G.; Chankeshwara, S. V.
Green Chem. 2007, 9, 1335–1340.
12
7. Mase, N.; Watanabe, K.; Yoda, H.; Takabe, K.; Tanaka, F.; Barbas, C. F., III. J. Am.
Chem. Soc. 2006, 128, 4966–4967.
8. (a) Breslow, R. Acc. Chem. Res. 1991, 24, 159–164; (b) Manabe, K.; Sun, X. M.;
Kobayashi, S. J. Am. Chem. Soc. 2001, 123, 10101–10102.
9. (a) Bhagat, S.; Sharma, R.; Sawant, D. M.; Sharma, L.; Chakraborti, A. K. J. Mol.
Catal. A: Chem. 2006, 244, 20–24; (b) Bhagat, S.; Sharma, R.; Chakraborti, A. K. J.
Mol. Catal. A: Chem. 2006, 260, 235–240.
22
10
12
66
65
S
O
23
10. Cogolli, P.; Maiolo, F.; Testaferri, L.; Tingoli, M.; Tiecco, M. J. Org. Chem. 1979,
44, 2642–2646.
11. Cogolli, P.; Maiolo, F.; Testaferri, L.; Tingoli, M.; Tiecco, M. J. Org. Chem. 1979,
44, 2636–2642.
12. (a) Hwu, J. R.; Wong, F. F.; Shiao, M.-J. J. Org. Chem. 1992, 57, 5254–5255; (b)
Shiao, M.-J.; Lai, L.-L.; Ku, W.-S.; Lin, P.-Y.; Hwu, J. R. J. Org. Chem. 1993, 58,
4742–4744.
a
The substrate (1 mmol) was treated with 2 (1.1 mmol) in the presence of SDS
(10 mol %) at 110 °C (oil-bath) in water (5 mL).
b
The yield of 1,3-diaryl-2,3-dihydro-1,5-benzothiazepine after chromatographic
purification.
c
The products were characterized by IR, NMR and MS.

G. Sharma et al. / Tetrahedron Letters 49 (2008) 4269–4271
4271
13. Hilhorst, E.; Chen, T. B. R. A.; Iskander, A. S.; Pandit, U. K. Tetrahedron 1994, 50,
7837–7848.
14. (a) Surdhar, P. S.; Armstrong, D. A. J. Phys. Chem. 1986, 90, 5915–5917; (b)
Ashby, E. C.; Park, W.-S.; Goel, A. B.; Su, W. Y. J. Org. Chem. 1985, 50, 5184–
5193.
15. (a) Gavande, N. S.; Kundu, S.; Badgujar, N. S.; Kaur, G.; Chakraborti, A. K.
Tetrahedron 2006, 62, 4201–4204; (b) Chakraborti, A. K.; Sharma, L.; Nayak, M.
K. J. Org. Chem. 2002, 67, 6406–6414; (c) Chakraborti, A. K.; Sharma, L.; Nayak,
M. K. J. Org. Chem. 2002, 67, 2541–2547; (d) Chakraborti, A. K.; Nayak, M. K.;
Sharma, L. J. Org. Chem. 2002, 67, 1776–1780; (e) Nayak, M. K.; Chakraborti, A.
K. Tetrahedron Lett. 1997, 38, 8749–8752.
J = 15.7 Hz, 1H), 7.78–7.87 (m, 5H), 8.02 (d, J = 8.3 Hz, 2H), 8.12 (d, J = 8.1 Hz,
2H). MS (EI) m/z: 354 (M+). Anal. Calcd for C17H13F3O3S: C, 57.62; H, 3.70; S,
9.05%. Found: C, 57.66; H, 3.71; S, 9.03%. Procedure for benzothiazepine
synthesis. 2,3-Dihydro-2,4-diphenyl-1,5-benzothiazepine (3) (Table 1, entry 1): A
mixture of 1 (0.21 g, 1 mmol) in water (5 mL) was heated under reflux (oil-bath
temp 110 °C) under magnetic stirring until it formed a melt admixed with
water as tiny liquid droplets after which 2 (0.13 g, 1.1 mmol, 1.1 equiv) was
added followed by SDS (29 mg, 10 mol %) and the mixture was stirred at 110 °C
for 12 h. The cooled (rt) reaction mixture was extracted with EtOAc (3 Â 5 mL),
the combined EtOAc extracts were washed with brine, dried (Na2SO4) and
concentrated under rotary vacuum evaporation. The crude product was
subjected to column chromatography (silica gel 60-120) using EtOAc/hexane
16. Pinchart, A.; Dallaire, C.; Bierbeek, A. V.; Gingras, M. Tetrahedron Lett. 1999, 40,
5479–5482.
(2:98) as eluent to afford 2,3-dihydro-2,4-diphenyl-1,5-benzothiazepine
3
17. Typical experimental procedure. Representative procedure for the synthesis of the
starting 1,3-diarylpropenones. 1-(4-methylsulfanylphenyl)-3-(4-methylphenyl)-
prop-2-enone (Table 1, entry 16): The starting 1,3-diarylpropenones were
prepared following the literature procedure.9 In a typical experiment 1-(4-
methylsulfanylphenyl)-ethanone (0.16 g, 1 mmol, 1 equiv) in EtOH (0.5 mL)
was treated with LiOHÁH2O (4 mg, 0.1 mmol, 10 mol %) under magnetic stirring
for 35 min at rt (ꢀ25–30 °C) followed by addition of 4-methylbenzaldehyde
(0.12 g, 1 mmol, 1 equiv). The mixture was stirred magnetically until complete
consumption of the starting materials (35 min, GCMS). After completion of the
reaction, a yellow precipitate was formed and this served as an indicator for
monitoring the reaction visually. EtOH was removed under reduced pressure.
The residue was diluted with water (5 mL), neutralized with 2% aqueous HCl
and extracted with EtOAc (3 Â 5 mL). The combined EtOAc extracts were
washed with brine solution (5 mL), dried (Na2SO4) and concentrated under
reduced pressure to afford 1-(4-methylsulfanylphenyl)-3-(4-methylphenyl)-
prop-2-enone (0.23 g, 87%). Yellow solid; mp 125–127 °C; IR (KBr): 1652, 1595,
(0.20 g, 65%) as a yellow solid, identical (spectral data and mp) with an
authentic compound.2j The remaining reactions were carried out following this
general procedure. All the product structures were in full agreement with the
spectral data (IR, NMR and MS) and gave satisfactory elemental analyses
(where applicable). The physical data (mp, IR, NMR, MS) of
a few
representative new compounds are provided. 2,3-Dihydro-2-(2-fluorophenyl)-
4-(4-chlorophenyl)-1,5-benzothiazepine (Table 1, entry 10): Yellow solid; mp
;
150–152 °C; IR (KBr) m: 1453, 1481, 1610, 1655 cmÀ1 1H NMR (CDCl3,
300 MHz) d: 2.93 (t, J = 12.8 Hz, 1H), 3.28 (dd, J = 4.6, 12.9 Hz, 1H), 5.37 (dd,
J = 4.6, 12.6 Hz, 1H), 7.02–7.25 (m, 3H), 7.27–7.30 (m, 2H), 7.45–7.56 (m, 4H),
7.66–7.69 (m, 1H), 8.04 (d, J = 8.6 Hz, 2H); 13C NMR (CDCl3, 75 MHz) d: 36.2,
52.6, 115.2, 115.5, 122.5, 124.5, 125.4, 125.7, 127.8, 128.3, 128.7, 129.2, 130.4,
135.1, 135.9, 137.3, 152.3, 156.9, 160.2, 167.5; MS (MALDI-TOF) m/z 368(MH+).
Anal. Calcd for C21H15ClFNS: C, 68.56; H, 4.11; N, 3.81; S, 8.72%. Found: C,
68.58; H, 4.13; N, 3.80; S, 8.71%. 2,3-Dihydro-2-(4-methylsulfonylphenyl)-4-(4-
trifluoromethylphenyl)-1,5- benzothiazepine (Table 1), entry 21: Yellow solid; mp
1338, 1224, 1093 cmÀ1
.
1H NMR (300 MHz, CDCl3): d 2.28 (s, 3H), 2.56 (s, 3H),
198–200 °C; IR (KBr) m: 1318, 1617, 1658 cmÀ1 1H NMR (CDCl3, 300 MHz) d:
;
7.22 (d, J = 7.8 Hz, 2H), 7.30 (d, J = 8.3 Hz, 2H), 7.45–7.55 (m, 3H), 7.79 (d,
3.05–3.13 (m, 4H), 3.31 (dd, J = 4.9, 13.0 Hz, 1H), 5.01 (dd, J = 4.7, 12.5 Hz, 1H),
7.18–7.35 (m, 2H), 7.49–7.52 (m, 3H), 7.60–7.62 (m, 1H), 7.76 (d, J = 8.2 Hz,
2H), 7.90 (d, J = 8.2 Hz, 2H), 8.16 (d, J = 8.1 Hz, 2H); 13C NMR (DMSO-d6,
75 MHz) d: 36.1, 43.3, 58.3, 121.4, 122.1, 123.9, 125.1, 125.8, 126.9, 127.2,
128.2, 129.3, 130.6, 131.0, 134.8, 139.8, 140.5, 146.3, 149.1, 151.6, 167.8; MS
(MALDI-TOF) m/z 462.7 (MH+). Anal. Calcd for C23H18F3NO2S2: C, 59.86; H,
3.93; N, 3.03; S, 13.90%. Found: C, 59.88; H, 3.96; N, 3.00; S, 13.92%. 7-Phenyl-
5,6,6a,7-tetrahydro-8-thia-13-aza-benzo[5,6]cyclohepta[1,2-a]naphthalene (Table
1, entry 23): Yellow solid; mp 165–167 °C; IR (KBr) m: 1449, 1484, 1589,
J = 15.6 Hz, 1H), 7.95 (d, J = 8.3 Hz, 2H). MS (EI) m/z: 268 (M+). Anal. Calcd for
C
17H16OS: C, 76.08; H, 6.01; S, 11.95%. Found: C, 76.10; H, 6.05; S, 11.93%. The
remaining diarylpropenones were prepared following this general procedure.
The physical data (IR, NMR, MS) of all known compounds were identical with
those in the literature.9a The physical data (IR, NMR, MS) of
a few
representative new compounds are provided below. 1-(4-Trifluoro-
methylphenyl)3-(4-methylsulfanylphenyl)prop-2-enone (Table 1, entry 17):
Yellow solid; mp 133–135 °C IR (KBr): 1653, 1596, 1333, 1125, 810 cmÀ1 1H
.
NMR (300 MHz, CDCl3): d 2.53 (s, 3H), 7.25-7.28 (m, 2H), 7.44 (d, J = 15.6 Hz,
1H), 7.56 (d, J = 8.3 Hz, 2H), 7.75-7.81 (m, 3H), 8.09 (d, J = 8.0 Hz, 2H). MS (EI)
m/z: 322 (M+). Anal. Calcd for C17H13F3OS: C, 63.34; H, 4.06; S, 9.95%. Found: C,
63.38; H, 4.10; S, 9.96%. 3-(4-Methanesulfonylphenyl)-1-(4-trifluoromethyl-
phenyl)prop-2-enone (Table 1, entry 21): An aqueous solution of OxoneÒ (50%
w/v, 3 mmol, 3 equiv) was added dropwise to a stirred solution of 1-(4-
2920 cmÀ1 1H NMR (CDCl3, 300 MHz) d: 1.42–1.47 (m, 1H), 1.85–1.94 (m, 1H),
;
2.68–2.74 (m, 1H), 3.01–3.12 (m, 1H), 3.35–3.39 (m, 1H), 4.78 (d, J = 12.3 Hz,
1H), 7.13–7.58 (m, 12H), 8.51 (d, J = 7.7 Hz, 1H); 13C NMR (CDCl3, 75 MHz) d:
24.8, 25.4, 43.3, 61.0, 123.7, 125.5, 125.9, 126.8, 127.4, 127.7, 128.4, 129.4,
130.4, 131.8, 132.5, 135.5, 140.4, 144.0, 152.9, 168.6. MS (EI) m/z 341 (M+).
Anal. Calcd for C23H19NS: C, 80.90; H, 5.61; N, 4.10; S, 9.39%. Found: C, 80.92; H,
5.63; N, 4.12; S, 9.38%.
trifluoromethylphenyl)-3-(4-methylsulfanylphenyl)prop-2-enone
(0.32 g,
1 mmol) in 1,4-dioxane (10 mL) at 0 °C. The reaction was allowed to proceed
with stirring at rt (ꢀ25–30 °C) for 4 h (TLC). The usual purification afforded a
white solid product (0.30 g, 85%); mp. 137-139 °C; IR (KBr): 1668, 1615, 1324,
18. (a) Narayan, S.; Muldoon, J.; Finn, M. G.; Fokin, V. V.; Kolb, H. C.; Sharpless, K. B.
Angew. Chem., Int. Ed 2005, 44, 3275–3279; (b) Klijn, J. E.; Engberts, J. B. F. N.
Nature 2005, 435, 746–747.
1146, 971, 826 cmÀ1 1H NMR (300 MHz, CDCl3):
. d 3.09 (s, 3H), 7.59 (d,