Regioselective addition of thiophenol to α,β-unsaturated N-acylbenzotriazoles

Article abstract of DOI:10.1016/j.tetlet.2011.07.057

Regioselective addition of thiophenol to α,β-unsaturated N-acylbenzotriazoles has been achieved by controlling the conditions. Thus, three types of products, namely α,β-unsaturated thioesters, β-thiophenoxy substituted N-acylbenzotriazoles, and β-thiophenoxy substituted thioesters were selectively obtained in good to excellent yields.

Full text of DOI:10.1016/j.tetlet.2011.07.057

Tetrahedron Letters 52 (2011) 4906–4910
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Regioselective addition of thiophenol to a,b-unsaturated N-acylbenzotriazoles
⇑
⇑
Ziming Xia, Xin Lv , Wencun Wang, Xiaoxia Wang
Zhejiang Key Laboratory for Reactive Chemistry on Solid Surfaces, College of Chemistry and Life Sciences, Zhejiang Normal University, Jinhua 321004, People’s Republic of China
a r t i c l e i n f o
a b s t r a c t
Article history:
Regioselective addition of thiophenol to
controlling the conditions. Thus, three types of products, namely
oxy substituted N-acylbenzotriazoles, and b-thiophenoxy substituted thioesters were selectively
obtained in good to excellent yields.
a
,b-unsaturated N-acylbenzotriazoles has been achieved by
,b-unsaturated thioesters, b-thiophen-
Received 26 May 2011
Revised 2 July 2011
Accepted 12 July 2011
Available online 21 July 2011
a
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Regioselective
a,b-Unsaturated N-acylbenzotriazole
Thiophenol
Michael addition
Acylation
Introduction
aryl-substituted NH being acylated (1,2-addition) while the unsub-
stituted NH attacked in a 1,4-mode at the same time.15 In most
Sulfur-containing compounds are important in bioorganic
chemistry and in medicinal areas for their antibiotic, antimicrobial,
anti-inflammatory, antitumor, and anti-HIV activities.1 Among
cases, the 1,2-and 1,4-selectivity was substrate-dependent. Tuning
the regioselectivity for the addition reaction of
a challenge.
a,b-acylBt remains
them,
a
,b-unsaturated thioesters show their attractive pharmaco-
Herein, we wish to report that thiophenol could undergo regio-
selective 1,2-addition (acylation), 1,4-addition (Michael addition)
logical properties such as antiatherogenic,2 antitubercular,3 and
antitumor4 activities; they are also employed for the assembly of
bioactive complex molecules.5 b-Thiophenoxy substituted amides
are medicinally useful.6 As a class of b-thiophenoxy substituted
amides, b-thiophenoxy substituted N-acylbenzotriazoles may pos-
sess potent biological activities. b-Thiophenoxy substituted thioes-
ters were reported as key intermediates for the synthesis of
valuable thioesters,7 and b-thiophenoxy substituted acids.8
and bis-addition (both the 1,2- and 1,4-addition) to
der controlled conditions (Scheme 1).
a,b-acylBt un-
In light of the fact that thiophenol could be acylated smoothly
by N-acylbenzotrizoles in the presence of triethylamine (TEA),16
the acylation of thiophenol with N-cinnamoyl benzotriazole was
carried out under the same conditions. In this case, a mixture of
a,b-unsaturated thioester 1a and b-thiophenoxy substituted thio-
a
,b-Unsaturated N-acylbenzotriazole (
a
,b-acylBt) is a class of
ester 1c was obtained (they were inseparable by column chroma-
tography) with a molar ratio of 2:3 (based on 1H NMR, see
Supplementary data) (Scheme 2).
Nevertheless, we fortunately found that ZnCl2/TEA could effi-
ciently promote the acylation with complete selectivity and 1a
could be obtained as the sole product.17 It was reasonable to pro-
pose that ZnCl2 chelated with the N-acylbenzotriazole moiety,
and meanwhile TEA deprotonated the thiophenol to form the more
nucleophilic thiolate (Scheme 3). The combination of these factors
possibly favored the 1,2-addition and led to the selective formation
useful unsaturated amides which contain both electron-withdraw-
ing carbon–carbon double bond moiety (for Michael addition) and
active amide moiety (for acylation).9 Therefore, it may act as a
Michael addition acceptor and/or an acylating reagent.10 The acyl-
ation of various N-,11 S-,12 and C-nucleophiles13 with
a
,b-acylBt has
,b-acylBt successfully
reacted with indoles,14a amines,14b and azlactones14c to afford the
corresponding 1,4-adducts. Bis-addition of binucleophile to ,b-
acylBt was also known. Although ,b-acylBt could smoothly acyl-
been realized with high efficiency. Besides,
a
a
a
ate hydrazine to form the corresponding
a
,b-unsaturated hydra-
of a,b-unsaturated thioesters. The presence of TEA is necessary for
zides,11a the reaction with arylhydrazines afforded unexpectedly
the 2-aryl-substituted pyrazolidin-3-ones in good yields with the
the good yields of 1a since a controlled experiment without TEA re-
sulted in poor conversion of the two substrates in 20 h regardless
of the presence of ZnCl2.
The generality of the reaction was subsequently investigated. As
⇑
Corresponding authors. Tel.: +86 0579 82283702 (X.L.); tel.: +86 0579
82282640; fax: +86 0579 82282269 (X.W.).
summarized in Table 1, the
a,b-acylBt with an electron-donating or
weak electron-withdrawing group on the aromatic ring afforded
E-mail addresses: lvxin@zjnu.cn (X. Lv), wangxiaoxia@zjnu.cn (X. Wang).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.07.057

Z. Xia et al. / Tetrahedron Letters 52 (2011) 4906–4910
4907
O
Conditions (A)
R1
SAr
(α,β-Unsaturated thioester)
Conjugate addition
R2
a
O
O
SAr
O
Conditions (B)
Conditions (C)
(
β
-Thiophenoxy substituted
R1
R1
Bt
ArSH
R1
Bt
+
N-acylbenzotriazole)
R2
SAr
b
R2
Acylation
(
β
-Thiophenoxy substituted
(α,β-Unsaturated acylBt)
SAr
thioester)
R2
c
Scheme 1. Regioselective addition of thiophenol to
a,b-unsaturated N-acylbenzotriazoles under controlled conditions.
O
O
SPh O
Table 1
TEA
ZnCl2/Et3N catalyzed acylation of thiophenol with
a
,b-unsaturated N-acylbenzotria-
SPh
+
Bt
PhSH
SPh
zolesa
THF Reflux
+
1a
1c
O
O
ZnCl2/Et3N
THF Reflux
Scheme 2. The addition of thiophenol to N-cinnamoyl benzotriazole in the
presence of TEA.
R
Bt
PhSH
R
SPh
+
a
Entry
1
R
Time (h)
12
Product
Yieldb (%)
ZnCl2
O
O
1a
72
N
R1
ZnCl2
N
N
R1
N
O
N
N
R2
R2
R1
SPh
2
7
2a
89
R2
N
CH3
N
SH
S
Et3N
3
4
5
12
8
3a
4a
5a
80
79
80
HN
MeO
Cl
Et3NH
Et3N ZnCl2
Scheme 3. Proposed mechanism for the selective formation of
a,b-unsaturated
thioesters.
7
Cl
good to excellent yields of the
a,b-unsaturated thioesters (entries
2–5 and 7), while the substrate with a strong electron-withdraw-
ing group (p-NO2) only gave moderate yield (entry 6). It was worth
mentioning that the acylation proceeded with high 1,2-addition
6
7
11
9
6a
7a
66
95
O2N
O
selectivity for all the aromatic
crotonoyl benzotriazole under the same conditions afforded the
bis-addition product in 48 h (Scheme 4). The expected ,b-unsatu-
a,b-acylBts examined. Interestingly,
a
a
Reaction conditions (A):
1.1 equiv), in dry THF (10 mL) with ZnCl2 (0.14 mmol, 20 mol %) and Et3N (1 mL) as
promoters, under reflux.
a,b-acylBt (0.7 mmol) and PhSH (0.77 mmol,
rated thioester was neither isolated nor detected. In contrast, the
1,4-adduct and bis-addition product were detected in the process.
In addition, the 1,4-adduct finally disappeared and transformed
into the bis-addition product completely. We postulated that
crotonoyl benzotriazole, with less hindrance at the b-position
(R1: methyl vs aryl in Scheme 3), preferably underwent the 1,4-
addition and subsequent acylation of thiolate occurred resulting
in the bis-addition product.
b
Isolated yield.
SPh
O
ZnCl2/Et3N
O
2 PhSH
1.2 eq
+
SPh
95% yield based on thiophenol
THF Reflux
48 h
Bt
We next turned our attention to achieving the selective 1,4-
addition between thiophenol and a,b-acylBt. Screening of the cat-
alysts found that a number of Lewis acids18 such as AlCl3, FeCl3,
Zn(OTf)2, and I2 were unsuitable for this selective thia-Michael
addition (a mixture of products a, b, and c with different ratios
was always obtained). When we employed silica gel,19 although
the desired reaction in anhydrous THF almost failed to occur (Table
2, entries 1 and 2), it did proceed selectively in wet THF. The cata-
lytic efficiency of silica gel was found to be highly dependent on
the water content. And further studies revealed the yield increased
remarkably when a suitable ratio of water was introduced as the
co-solvent (entry 3). It was established that the optimal volume ra-
tio of THF and H2O was 9:1 (entries 1–5). The presence of higher
Scheme 4. ZnCl2/Et3N promoted bis-addition of thiophenol to crotonoyl
benzotriazole.
content of water suppressed the yield (entries 4 and 5). The molar
ratio of the substrates was also optimized, and good yield was ob-
tained by employing 1.4 equiv of thiophenol (entries 3 and 6–8).
The selectivity and yield for 1b could be further improved by low-
ering the temperature (although longer reaction time was re-
quired) (entries 7, 9, and 10), and À20 °C was chosen as the most
suitable temperature (entry 10).

4908
Z. Xia et al. / Tetrahedron Letters 52 (2011) 4906–4910
Table 2
Table 3
Silica gel promoted conjugate addition of thiophenol to N-cinnamoyl benzotriazole
Silica gel/H2O promoted conjugate addition between thiophenol and
a
,b-acylBta
under different conditionsa
O
SPh
O
SPh
O
O
Silica gel
R1
Bt
PhSH
R1
Bt
+
Silica gel
Bt
Bt
PhSH
+
R2
R1
R2
b
THF/H2O -20
C
THF/H2O Temp
1b
Entry
1
R2
H
Time (h)
12
Product
Yieldb (%)
80
The effect of water content
80
1b
60
40
20
0
2
H
24
2b
62
CH3
3
4
5
H
H
H
1.0
0.5
0.2
3b
4b
5b
91
86
90
0
trace 10
20
50
Cl
Cl
Water content (%)
Entry
a
,b-acylBt/PhSHb
THF: H2Oc
T (°C)
Time (h)
Yieldd (%)
1
2
3
4
5
6
7
8
9
1:1.2
1:1.2
1:1.2
1:1.2
1:1.2
1:1.3
1:1.4
1:1.5
1:1.4
1:1.4
THFe
THFf
9:1
8:2
5:5
9:1
9:1
9:1
9:1
9:1
0
0
0
0
0
0
0
0
10
10
1.5
1.5
3
1
1
1
1
Trace
n.d.g
77
73
49
77
78
71
53
Cl
6
7
H
H
0.2
0.5
6b
7b
86
81
O2N
rt
À20
10
12
84
a
Reaction conditions:
a,b-acylBt (1 mmol), PhSH (1.2–1.6 mmol), and silica
Br
Me
H
(GF254, 200–300 mesh, 0.4 g, dried), in THF or THF/H2O (10 mL), at T °C for the
8
9
H
Me
0.2
0.1
8b
9b
89
84
indicated time.
b
Molar ratio.
Volume ratio.
c
d
Yield based on HPLC (for details, see Supplementary data).
Commercial THF without any treatment.
10
11
H
H
0.3
2.5
10b
11b
90
86
e
CF3
F
f
Dry THF.
Not detected.
g
With the optimized conditions, we then explored the 1,4-addi-
c
12
13
H
H
72
72
—
—
—
tion reactions of various
tion was applicable to a variety of substrates and provided the
desired Michael adducts in good to excellent yields. The ,b-acylBt
a,b-acylBt. As shown in Table 3, the reac-
MeO
O
d
a
—
with electron-withdrawing groups on the aromatic ring performed
better than those with electron-donating groups (entries 3–7 and
a
Reaction conditions (B):
a,b-acylBt (1.0 mmol), PhSH (1.4 mmol), and silica
10–11). The
provided excellent yield (entry 5). Aliphatic
ble to the addition reaction as well (entries 8 and 9). The
4-methoxyphenyl- and 2-furyl- substituted ,b-acylBt reacted
a
,b-acylBt with an ortho-substituted aryl group also
(G254, 200–300 mesh, 0.4 g), in THF/H2O (9:1, v:v, 10 mL), at À20 °C.
b
Isolated yield.
a
,b-acylBt was amena-
c
1H NMR spectrum showed that the product was a mixture of the starting
a,b-
acylBt, the b-thiophenoxy substituted N-acylbenzotriazole b, and the b-thiophen-
a
oxy substituted thioester c with the ratio 4:1.2:1 (see Supplementary data).
d
1H NMR spectrum showed that the product was a mixture of the starting
a,b-
much less efficiently and may even afford a mixture of several
products (entries 12 and 13). The reason may be that the two elec-
tron-rich aryls weakened the electrophilicity of the b-position and
make the 1,4-addition difficult.
acylBt and the b-thiophenoxy substituted N-acylbenzotriazole b with the ratio 3:1
(inseparable by column chromatography).
Although the detailed mechanism of the reaction remains to be
explored, water should play an important role in the regioselective
1,4-addition. Recently, water was found to be a good solvent for
the thia-Michael addition of thiols to enones.20 Taking account of
the action of silica gel21 and water, a plausible mechanism was
proposed (Fig. 1). The water absorbed on the surface of the silica
gel forms hydrogen bonds with the hydroxyls of the silica gel. Thus
the hydroxyls could readily form a hydrogen bond between the
SiO2
O
H
H
H
O
H
O
O
H
H
H
carbonyl of a,b-acylBt and the –SH of the thiophenol. Two suitably
O
Ph
S
located hydroxyls of the silica gel could activate the two substrates
concurrently and make the 1,4-addition electronically and region-
ally favorable.
Bt
R
Finally, we attempted to extend this method to the one-pot syn-
thesis of b-thiophenoxy substituted thioesters. Considering that N-
Figure 1. Proposed mechanism for the selective 1,4-addition catalyzed by SiO2/
H2O.

Z. Xia et al. / Tetrahedron Letters 52 (2011) 4906–4910
4909
O
acylbenzotriazoles are an efficient S-acylating reagent, we postu-
lated that product b could further acylate thiophenol to achieve
the bis-addition.
R1
SPh
a
Path A
Path B
R2
SPh
O
SPh O
R2
The reaction of 2.5 equiv of thiophenol with N-cinnamoyl ben-
zotriazole showed that under the same conditions, the desired
product 1c could be obtained in 63% yield accompanied with the
side reaction of hydrolysis of the N-acylbenzotriazole moiety.
Therefore, to minimize the hydrolysis, anhydrous conditions were
applied in this case. To our delight, good to excellent yields of b-
thiophenoxy substituted thioesters were obtained with silica gel
as the catalyst in refluxing anhydrous THF (using 2.5 equiv of thio-
phenol), and the results are summarized in Table 4. Both electron-
donating and electron-withdrawing groups on the aryl could be
PhSH
PhSH
R1
Bt
O
Silica gel R1
Reflux
SPh
R2
R1
Bt
b
c
R2
Scheme 5. Probable routes for the formation of b-thiophenoxy substituted
thioesters catalyzed by SiO2.
conversion of 2a was much lower (about 68% of 2a was recovered
after 30 h) while 2b could be consumed completely in 1.5 h to af-
ford 2c in 89% yield. Based on the above experiments, we propose
that the formation of c should proceed mainly via Path B (Scheme
5).
tolerated (entries 1–7). Aliphatic
a,b-acylBt gave relatively lower
yields (entries 8 and 9). 2-Furanyl substituted
a,b-acylBt afforded
an inseparable mixture (entry 10).
Although b-thiophenoxy substituted thioesters
c
could be
formed via b by further acylation (Scheme 5, Path B). The possibil-
ity for the formation of c by an alternative way was also investi-
gated (Scheme 5, Path A). Thus b-thiophenoxy substituted
In summary, we have developed a facile and efficient protocol
for the regioselective addition of thiophenol to
a,b-unsaturated
N-acylbenzotriazoles. Thus a variety of ,b-unsaturated thioesters,
a
N-acylbenzotriazle 2b and
a,b-unsaturated thioester 2a were
b-thiophenoxy substituted N-acylbenzotriazoles and b-thiophen-
oxy substituted thioesters could be prepared, respectively, in good
to excellent yields under controlled conditions.22 The readily avail-
able catalysts, facile procedures, and potentially valuable products
would make the methods practical and useful to synthetic chem-
ists. Besides, the mechanism for the regioselectivity was discussed
and it may provide an additional hint for the regioselective control
of 1,2-, 1,4-, and bis-addition between other nucleophiles and elec-
tron-deficient alkenes. The application of the 1,4-adducts b-thio-
phenoxy substituted N-acylbenzotriazoles in the synthesis of
structurally more versatile compounds is currently undergoing in
our lab.
mixed, respectively, with 1.2 equiv of thiophenol using silica gel
as the promoter in refluxing THF. Interestingly, both of the
reactions afforded product 2c successfully. Nevertheless, the
Table 4
Silica gel catalyzed reaction of thiophenol with a,b-unsaturated N-acylbenzotriazoles
to afford b-thiophenoxy substituted thioestera
O
SPh
O
Silica gel
R1
Bt
2PhSH
R1
SPh
+
THF Reflux
R2
R1
R2
c
Acknowledgment
Entry
1
R2
H
Time (h)
10
Product
Yieldb (%)
81
This work was financially supported by the National Natural
Science Foundation of China (No. 20802070).
1c
Supplementary data
2
3
4
5
H
H
H
H
11
11
8
2c
3c
4c
5c
82
77
87
85
CH3
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2011.07.057.
MeO
Cl
References and notes
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6
7
H
6
6c
7c
88
83
O2N
H
H
9
2
Br
Me
H
8
9
8c
9c
79
66
Me
1.5
c
10
H
7
—
—
O
a
Reaction conditions (C):
and silica (G254, 200–300 mesh, 0.4 g), in THF (10 mL), under reflux.
a,b-acylBt (0.7 mmol), PhSH (1.75 mmol, 2.5 equiv),
b
Isolated yield.
1H NMR spectrum showed that the product was a mixture of b-thiophenoxy
c
substituted thioester c and
rable by column chromatography).
a,b-unsaturated thioester a with the ratio 3:4 (insepa-

4910
Z. Xia et al. / Tetrahedron Letters 52 (2011) 4906–4910
9. Katritzky, A. R.; Suzuki, K.; Wang, Z. Synlett 2005, 1656.
dry THF (10 mL) was added PhSH (0.77 mmol) and Et3N (1 mL). The mixture
was stirred under reflux until completion of the reaction (detected by TLC).
Then aq HCl (0.1 N, 5 mL) and EtOAc (50 mL) was added. The combined organic
phase was washed with satd Na2CO3, then with brine, dried over anhydrous
Na2SO4, and concentrated under vacuum. The residue was purified by flash
chromatography on silica gel to give the pure product.
10. It is noteworthy that N-acylbenzotriazoles are relatively stable, and show their
superiority when the corresponding acid chlorides are difficult or unstable to
synthesize. For examples, see: (a) Katritzky, A. R.; Avan, I.; Tala, S. R. J. Org.
Chem. 2009, 74, 8690; (b) Katritzky, A. R.; Sakhuja, R.; Khelashvili, L.; Shanab, K.
J. Org. Chem. 2009, 74, 3062; (c) Katritzky, A. R.; Tala, S. R.; Abo-Dya, N. E.;
Gyanda, K.; El-Gendy, B. E. M. J. Org. Chem. 2009, 74, 7165; (d) Katritzky, A. R.;
Huang, L.; Sakhuja, R. Synthesis 2010, 2011.
General procedure for the synthesis of b-thiophenoxy N-acylbenzotriazoles (b).To a
solution of
a,b-unsaturated N-acylbenzotriazole (1.0 mmol) and silica gel
11. For example, see (a) Katritzky, A. R.; Wang, M.; Zhang, S. Arkivoc 2001, 19; (b)
Katritzky, A. R.; Cai, C.; Singh, S. K. J. Org. Chem. 2006, 71, 3375; (c) Katritzky, A.
R.; Widyan, K.; Kirichenko, K. J. Org. Chem. 2007, 72, 5802; (d) Katritzky, A. R.;
Hanci, S.; Meher, N. K. Arkivoc 2009, 115; (e) Katritzky, A. R.; Gyanda, R.;
Meher, N. K.; Song, Y. Heterocycl. 2009, 77, 1249; (f) Wang, X. X.; He, L.; Li, Z. F.;
Wang, W. C.; Liu, J. H. Synth. Commun. 2009, 39, 819.
(0.4 g) in THF (9 mL), was added PhSH (1.4 mmol) and H2O (1 mL). The mixture
was stirred at À20 °C until completion of the reaction (detected by TLC). The
silica gel was removed by filtration, and the filtrate was washed with EtOAc
(three times). The combined organic phase was washed with satd Na2CO3, then
with brine, dried over anhydrous Na2SO4 and concentrated under vacuum. The
residue was purified by flash chromatography on silica gel to give the pure
product.
12. Wang, X. X.; Zou, X. F.; Du, J. X. J. Chem. Res. 2006, 64.
13. For examples, see: (a) Katritzky, A. R.; Meher, N. K.; Singh, S. K. J. Org. Chem.
2005, 70, 7792; (b) Katritzky, A. R.; Le, K. N. B.; Khelashvili, L.; Mohapatra, P. P.
J. Org. Chem. 2006, 71, 9861.
14. (a) Zou, X. F.; Wang, X. X.; Cheng, C. G.; Kong, L. C.; Mao, H. Tetrahedron Lett.
2006, 47, 3767; (b) Wang, X. X.; Li, Z. F.; Zhu, X. M.; Mao, H.; Zou, X. F.; Kong, L.
C.; Li, X. S. Tetrahedron 2008, 64, 6510; (c) Uraguchi, D.; Ueki, Y.; Ooi, T. Science
2009, 326, 120.
15. Wang, X. X.; Wang, W. C.; Wen, Y. H.; He, L.; Zhu, X. M. Synthesis 2008, 3223.
16. Katritzky, A. R.; Shestopalov, A. A.; Suzuki, K. Synthesis 2004, 1806.
17. Preliminary screening experiments also employed other promoters such as
TEA, SmI3 and TiCl4. However, in each above case, a mixture of 1a and 1c was
obtained with low regioselectivity.
18. Several recent representative examples for Lewis acid catalyzed thia-Michael
additions: (a) Garg, S. K.; Kumar, R.; Chakraborti, A. K. Synlett 2005, 1370; (b)
Garg, S. K.; Kumar, R.; Chakraborti, A. K. Tetrahedron Lett. 2005, 46, 1721; (c)
Chu, C.-M.; Huang, W.-J.; Lu, C. W.; Wu, P.; Liu, J.-T.; Yao, C.-F. Tetrahedron Lett.
2006, 47, 7375; (d) Gao, S. J.; Tzeng, T. K.; Sastry, M. N. V.; Chu, C.-M.; Liu, J.-T.;
Lin, C. C.; Yao, C.-F. Tetrahedron Lett. 2006, 47, 1889; (e) Chu, C.-M.; Gao, S. J.;
Sastry, M. N. V.; Kuo, C.-W.; Lu, C. W.; Liu, J.-T.; Yao, C.-F. Tetrahedron Lett. 2007,
63, 1863; (f) Khatik, G. L.; Kumar, R.; Chakraborti, A. K. Synthesis 2007, 541; (g)
Sharma, G.; Kumar, R.; Chakraborti, A. K. J. Mol. Catal. A: Chem. 2007, 263, 143;
(h) Sreedhar, B.; Reddy, M. A.; Reddy, P. S. Synlett 2008, 1949.
General procedure for the synthesis of b-thiophenoxy thioesters (c). To a solution
of a,b-unsaturated N-acylbenzotriazole (0.7 mmol) and silica gel (0.4 g) in dry
THF (10 mL) was added PhSH (1.75 mmol). The mixture was stirred under
reflux until completion of the reaction (detected by TLC). The silica gel was
removed by filtration, and the filtrate was washed with EtOAc (three times).
The combined organic phase was washed with satd Na2CO3, then with brine,
dried over anhydrous Na2SO4 and concentrated under vacuum. The residue
was purified by flash chromatography on silica gel to give the pure product.
Selected spectral data of the products: (E)-S-Phenyl 3-phenylprop-2-enethioate
(1a). White solid; mp 93–94 °C; IR (KBr) v 3060, 3024, 1677, 1613, 1574, 1477,
1437, 1328, 1305, 1019, 766, 687, 572 cmÀ1 1H NMR (400 MHz, CDCl3) d 7.69
;
(d, J = 15.8 Hz, 1H), 7.57–7.58 (m, 2H), 7.41–7.51 (m, 8H), 6.80 (d, J = 15.8 Hz,
1H); 13C NMR (100 MHz, CDCl3) d 188.1, 141.6, 134.7, 134.0, 130.8, 129.5,
129.3, 129.1, 129.0, 128.5, 124.1.
1-(1H-1,2,3-Benzotriazol-1-yl)-3-phenyl-3-(phenylthio)-propan-1-one
White solid; mp 106–108 °C; IR (KBr) v 3063, 3026, 2976, 2910, 2891, 1738,
1618, 1597, 1487, 1451, 1390, 1355 cmÀ1 1H NMR (400 MHz, CDCl3) d 8.20 (d,
(1b).
;
J = 8.0 Hz, 1H), 8.11 (d, J = 8.0 Hz, 1H), 7.60–7.64 (m, 1H), 7.47–7.51 (m, 1H),
7.35–7.39 (m, 4H), 7.21–7.30 (m, 6H), 5.03 (t, J = 7.4 Hz, 1H), 4.03–4.16 (m,
2H); 13C NMR (100 MHz, CDCl3) d 169.5, 146.2, 140.1, 133.5, 133.4, 131.0,
130.4, 129.0, 128.9, 128.6, 128.0, 127.8, 126.3, 120.2, 114.5, 48.7, 41.9; MS (EI)
m/z 359 (M+); HRMS (EI) m/z calcd for C21H17N3OS: 359.1092 (M+); found:
359.1089 (M+).
19. Silica gel promoted thia-Michael addition: (a) Firouzabadi, H.; Iranpoor, N.;
Jafarpour, M.; Ghaderi, A. J. Mol. Catal. A: Chem. 2006, 249, 98; (b) Khatik, G. L.;
Sharma, G.; Kumar, R.; Chakraborti, A. K. Tetrahedron 2007, 63, 1200; (c)
Sharma, G.; Kumar, R.; Chakraborti, A. K. Tetrahedron Lett. 2008, 49, 4272.
20. Khatik, G. L.; Kumar, R.; Chakraborti, A. K. Org. Lett. 2006, 8, 2433.
21. (a) Minakata, S.; Komatsu, M. Chem. Rev. 2009, 109, 711; (b) Bianchini, C.;
Burnaby, D. G.; Evans, J.; Frediani, P.; Meli, A.; Oberhauser, W.; Psaro, R.;
Sordelli, L.; Vizza, F. J. Am. Chem. Soc. 1999, 121, 5961.
S-Phenyl-3-phenyl-3-(phenylthio)propanethioate (1c). White solid; mp 84–
86 °C; IR (KBr) v 3056, 2923, 1703, 1612, 1582, 1513, 1476 cmÀ1 1H NMR
;
(400 MHz, CDCl3) d 7.35–7.39 (m, 5H), 7.26–7.31 (m, 10H), 4.75–4.80 (m, 1H),
3.28–3.31 (m, 2H); 13C NMR (100 MHz, CDCl3) d 194.7, 140.0, 134.4, 133.7,
133.2, 129.5, 129.2, 129.0, 128.6, 127.88, 127.86, 127.8, 127.3, 49.4, 49.3; MS
(EI) m/z 350 (M+); HRMS (EI) calcd for C21H18OS2: 350.0799 (M+); found:
350.0800 (M+).
22. General procedure for the synthesis of
a,b-unsaturated thioesters (a). To a solution
of a,b-unsaturated N-acylbenzotriazole (0.7 mmol) and ZnCl2 (0.14 mmol) in