Isoquinoline-mediated S-vinylation and N-vinylation of benzo[d]oxazole-2- thiol and benzo[d]thiazole-2-thiol

Article abstract of DOI:10.1016/j.cclet.2011.10.001

An effective route to S-vinylated and N-vinylated benzo[d]oxazole-2(3H)- thiones and benzo[d]thiazole-2(3H)-thiones is described via reaction of acetylenic esters and benzo[d]oxazole-2-thiol and benzo[d]thiazole-2-thiol in the presence of 15 mol% of isoquinoline.

Full text of DOI:10.1016/j.cclet.2011.10.001

Available online at www.sciencedirect.com
Chinese Chemical Letters 23 (2012) 5–8
www.elsevier.com/locate/cclet
Isoquinoline-mediated S-vinylation and N-vinylation of
benzo[d]oxazole-2-thiol and benzo[d]thiazole-2-thiol
*
Issa Yavari , Samira Nasiri-Gheidari, Anvar Mirzaei
Department of Chemistry, Tarbiat Modares University, PO Box 14115-175, Tehran, Iran
Received 23 May 2011
Available online 8 November 2011
Abstract
An effective route to S-vinylated and N-vinylated benzo[d]oxazole-2(3H)-thiones and benzo[d]thiazole-2(3H)-thiones is described
via reaction of acetylenic esters and benzo[d]oxazole-2-thiol and benzo[d]thiazole-2-thiol in the presence of 15 mol% of isoquinoline.
# 2011 Issa Yavari. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: S-Vinylation; N-Vinylation; Acetylenic esters; Benzo[d]oxazole-2-thiol; Benzo[d]thiazole-2-thiol; Isoquinoline
The development of new methods for catalytic C–N bond formation is highly challenging [1]. A variety of active
metal catalyst systems have been reported for the N-arylation of amines, amides, azoles, and carbamates [2,3].
However, there exist fewer examples of C–N bond formation as a method of N-vinylation [4,5]. Reports concerning
the N-vinylation of amides and carbamates are even less common as compared to reports of N-vinylation of amines
[6,7]. However, research in the field of carbon–sulfur coupling reactions has lagged behind, largely because of sulfur’s
long-standing reputation as a catalyst poison [8,9]. Only a handful of publications describe the vinylation of thiols
[10,11]. Here we report simple one-pot method for S-vinylation and N-vinylation of benzo[d]oxazole-2(3H)-thiones
and benzo[d]thiazole-2(3H)-thiones in the presence of isoquinoline as a catalyst.
1. Experimental
Compounds 1, 2 and 9 were obtained from Merck and were used without further purification. Mp: Electrothermal-
9100 apparatus; uncorrected. IR spectra: Shimadzu IR-460 spectrometer. 1H and 13C NMR spectra: Bruker DRX-500
Avance instrument; in CDCl3 at 500 and 125 MHz, respectively; EI-MS (70 eV): Finnigan-MAT-8430 mass
spectrometer, in m/z. Elemental analyses (C, H, N) were performed with a Heraeus CHN-O-Rapid analyzer.
1.1. General procedure for the preparation of compounds 3
To a stirred solution of 1 (0.151 g, 1 mmol) and 2 (1 mmol) in CH2Cl2 (10 mL), a solution of isoquinoline
(0.25 mmol) in CH2Cl2 (2 mL) was added. The reaction mixture was stirred for 2–4 h. The solvent was removed under
* Corresponding author.
E-mail address: yavarisa@modares.ac.ir (I. Yavari).
1001-8417/$ – see front matter # 2011 Issa Yavari. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2011.10.001

6
I. Yavari et al. / Chinese Chemical Letters 23 (2012) 5–8
reduced pressure, and the residue was purified by flash column chromatography (SiO2; hexane/AcOEt 4:1) to afford
the pure title compounds. Compound 12a is known [12].
Dimethyl 2-(2-thioxobenzo[d]oxazol-3(2H)-yl) f umarate (3a): Yellow powder, yield: 0.27 g (92%), mp: 130–
132 8C. IR (KBr): 1731 (C O), 1729 (C O) cmÀ1. 1H NMR (CDCl3): d 3.64 (s, 3 H, MeO), 3.85 (s, 3 H, MeO), 6.83–
6.86(m, 1H, CH), 7.25–7.27(m, 2H, 2CH), 7.33(s,1H, CH), 7.37–7.39(m, 1H, CH). 13CNMR(CDCl3):d52.7(MeO),
53.6 (MeO), 109.8 (CH), 110.7 (CH), 124.6 (CH), 125.0(CH), 130.1(CH), 131.9 (C), 133.8(C), 147.9(C), 161.3 (C O),
162.2 (C O), 179.6 (C S). MS (EI, 70 eV): m/z (%) 293 (M+, 10), 262 (8), 235 (100), 207 (60), 163 (5), 150 (6), 76 (10).
Anal. Calcd. for C13H11NO5S (293.29): C, 53.24%; H, 3.78%; N, 4.78%. Found: C, 53.23%; H, 3.75%; N, 4.80%.
Diethyl 2-(2-thioxobenzo[d]oxazol-3(2H)-yl) f umarate (3b): Yellow powder, yield: 0.28 g (86%), mp: 110–
112 8C. IR (KBr): 1732 (C O), 1729 (C O) cmÀ1. 1H NMR (CDCl3): d 1.03 (t, 3 H, Me), 1.30 (t, 3 H, Me), 4.07 (m,
2H, OCH2), 4.30–4.37 (m, 2 H, OCH2), 6.84–6.87 (m, 1 H, CH), 7.23–7.26 (m, 2 H, 2 CH), 7.36 (s, 1 H, CH), 7.37–
7.39 (m, 1 H, CH). 13C NMR (CDCl3): d 13.6 (Me), 14.0 (Me), 61.9 (OCH2), 62.8 (OCH2), 109.8 (CH), 110.0 (CH),
124.5 (CH), 125.0 (CH), 130.6 (CH), 132.2 (C), 133.7 (C), 147.9 (C), 160.8 (C O), 161.9 (C O), 179.5 (C S). MS
(EI, 70 eV): m/z (%) 321 (M+, 11), 276 (10), 248 (100), 220 (75), 176 (13), 150 (6), 76 (7). Anal. Calcd. for
C15H15NO5S (321.34): C, 56.07%; H, 4.70%; N, 4.36%. Found: C, 56.11%; H, 4.75%; N, 4.40%.
Di-tert-butyl 2-(2-thioxobenzo[d]oxazol-3(2H)-yl) f umarate (3c): Yellow powder, yield: 0.31 g (82%), mp: 97–
99 8C. IR (KBr): 1737 (C O), 1728 (C O) cmÀ1. 1H NMR (CDCl3): d 1.08 (s, 9 H, Me3C), 1.25 (s, 9 H, Me3C), 6.84–
6.87 (m, 1 H, CH), 7.25–7.28 (m, 2 H, 2 CH), 7.37 (s, 1 H, CH), 7.38–7.40 (m, 1 H, CH). 13C NMR (CDCl3): d 27.4
(Me3C), 28.3 (Me3C), 79.7 (OCMe3), 80.1 (OCMe3), 109.4 (CH), 110.9 (CH), 124.1 (CH), 125.1 (CH), 130.4 (CH),
131.7 (C), 134.0 (C), 147.7 (C), 161.2 (C O), 162.5 (C O), 179.9 (C S). MS (EI, 70 eV): m/z (%) 377 (M+, 3), 305
(11), 277 (100), 249 (55), 205 (30), 150 (9), 76 (13). Anal. Calcd. for C19H23NO5S (377.45): C, 60.46%; H, 6.14%; N,
3.71%. Found: C, 60.40%; H, 6.20%; N, 3.74%.
Dimethyl 2-(2-thioxobenzo[d]thiazol-3(2H)-yl) f umarate (3d): Pale yellow crystals, yield: 0.27 g (87%), mp: 124–
126 8C. IR (KBr): 1731 (C O), 1727 (C O) cmÀ1. 1H NMR (CDCl3): d 3.60 (s, 3 H, MeO), 3.84 (s, 3 H, MeO), 6.95
(s, 1 H, CH), 7.37 (t, 1 H, 3J = 7.3, CH), 7.47 (t, 1 H, 3J = 7.4, CH), 7.81 (d, 1 H, 3J = 8.0, CH), 7.93 (d, 1 H, 3J = 8.1,
CH). 13C NMR (CDCl3): d 52.3 (MeO), 53.4 (MeO), 121.0 (CH), 122.4 (CH), 125.2 (CH), 127.0 (C), 130.7 (C), 136.2
(CH), 141.6 (C), 153.0 (CH), 164.2 (C O), 164.8 (C O), 179.1 (C S). MS (EI, 70 eV): m/z (%) 309 (M+, 14), 278
(10), 250 (100), 222 (75), 178 (10), 166 (6), 76 (9). Anal. Calcd. for C13H11NO4S2 (309.35): C, 50.47%; H, 3.58%; N,
4.53%. Found: C, 50.49%; H, 3.60%; N, 4.58%.
Di-tert-butyl 2-(2-thioxobenzo[d]thiazol-3(2H)-yl) f umarate (3e): Pale yellow powder, yield: 0.32 g (81%), mp:
117-119 8C. IR (KBr): 1733 (C O), 1726 (C O) cmÀ1. 1H NMR (CDCl3): d 1.1 (s, 9 H, Me3C), 1.30 (s, 9 H, Me3C),
3
3
3
7.0 (s, 1 H, CH), 7.35 (t, 1 H, J = 7.2, CH), 7.44 (t, 1 H, J = 7.4, CH), 7.84 (d, 1 H, J = 8.1, CH), 7.92 (d, 1 H,
3J = 8.3, CH), 13C NMR (CDCl3): d 27.4 (Me3C), 28.3 (Me3C), 79.7 (OCMe3), 80.1 (OCMe3), 121.2 (CH), 122.1
(CH), 125.3 (CH), 127.0 (C), 130.5 (C), 136.4 (CH), 141.3 (C), 153.2 (CH), 162.1 (C O), 164.6 (C O), 178.9 (C S).
MS (EI, 70 eV): m/z (%) 393 (M+, 6), 320 (10), 292 (100), 264 (45), 220 (10), 166 (8), 76 (10). Anal. Calcd. for
C19H23NO4S2 (393.51): C, 57.99%; H, 5.89%; N, 3.56%. Found: C, 58.22%; H, 5.95%; N, 3.64%.
Methyl (Z)-3-(benzo[d]oxazol-2-ylthio)acrylate (10a): White powder, yield: 0.10 g (44%), mp: 122–124 8C. IR
(KBr): 1738 (C O) cmÀ1. 1H NMR (CDCl3): d 3.83 (s, 3 H, Me), 6.23 (d, 1 H, 3J = 9.9, CH), 7.34–7.36 (m, 2 H, 2
CH), 7.51–7.53 (m, 1 H, CH), 7.68–7.69 (m, 1 H, CH), 8.23 (d, 1 H, 3J = 9.9, CH). 13C NMR (CDCl3): d 52.0 (Me),
110.4 (CH), 119.3 (CH), 120.9 (CH), 124.9 (CH), 125.0 (CH), 139.7 (CH), 151.9 (C), 152.0 (C), 162.7 (C N), 166.8
(C O). MS (EI, 70 eV): m/z (%) 235 (M+, 8), 204 (12), 176 (100), 150 (10), 76 (6). Anal. Calcd. for C11H9NO3S
(235.25): C, 56.16%; H, 3.86%; N, 5.95%. Found: C, 56.20%; H, 3.90%; N, 5.99%.
Methyl (E)-3-(benzo[d]oxazol-2-ylthio)acrylate (11a): White powder, yield: 0.12 g (56%), mp: 120–122 8C. IR
(KBr): 1741 (C O) cmÀ1. 1H NMR (CDCl3): d 3.81 (s, 3 H, Me), 6.32 (d, 1 H, 3J = 15.8, CH), 7.31–7.33 (m, 2 H, 2
CH), 7.50–7.51 (m, 1 H, CH), 7.65–7.67 (m, 1 H, CH), 8.30 (d, 1 H, 3J = 15.8, CH). 13C NMR (CDCl3): d 51.9 (Me),
110.3 (CH), 116.6 (CH), 119.0 (CH), 124.6 (CH), 124.7 (CH), 137.6 (CH), 141.6 (C), 151.2 (C), 159.3 (C N), 164.6
(C O). MS (EI, 70 eV): m/z (%) 235 (M+, 8), 204 (12), 176 (100), 150 (10), 76 (6). Anal. Calcd. for C11H9NO3S
(235.25): C, 56.16%; H, 3.86%; N, 5.95%. Found: C, 56.20%; H, 3.90%; N, 5.99%.
Ethyl 4-oxo-4H-[1,3]thiazino[3,2-a]benzimidazole-2-carboxylate (12b): Yellow powder, yield: 0.25 g (91%), mp:
1
3
161–163 8C. IR: 1692 (C O) cmÀ1. H NMR (500 MHz, CDCl3): d 1.38 (t, 3H, J = 6.9 Hz, Me), 4.37 (q, 2H,
3
3J = 7.1 Hz, OCH2), 7.19–7.20 (m, 1H, CH), 7.26–7.38 (m, 2H, 2 CH), 7.65 (d, 1H, J = 7.8 Hz, CH), 7.93 (d, 1H,
3J = 7.6 Hz, CH). 13C NMR (75 MHz, CDCl3): d 13.6 (Me), 61.8 (OCH2), 112.3 (CH), 119.5 (CH), 121.6 (CH), 124.3

I. Yavari et al. / Chinese Chemical Letters 23 (2012) 5–8
RO2C
7
CO2R
Isoquinoline
15 mol%
CO2R
N
X
N
X
SH
S
+
2-4 h, rt
CO2R
R
Yilde (%)
X
O
O
O
S
R
3a
3b
3c
3d
3e
X
O
S
Me
Et
92
86
82
87
81
2a
1a
1b
Me
Et
2b
2c
t-Bu
Me
t-Bu
t-Bu
S
Scheme 1.
(CH), 125.9 (CH), 129.6 (C), 144.1 (C), 148.5 (C), 154.6 (C), 157.1 (C O), 164.7 (C O). MS (EI, 70 eV): m/z (%) 274
(M+, 100), 229 (22), 201 (40), 174 (60), 129 (30). Anal. Calcd. for C13H10N2O3S (274.30): C, 56.92%; H, 3.67%; N,
10.21%. Found: C, 56.70%; H, 3.53%; N, 10.09%.
2. Results and discussion
The reaction of 2-mercaptobenzoxazol and 2-mercaptobenzothiazol with acetylenic esters 2 in the presence of
15 mol% of isoquinoline proceeded at r.t. in CH2Cl2 and was finished after 2–4 h. Any product other than 3 could not
be detected by NMR spectroscopy. The structures of compounds 3a–e were deducted from their IR, 1H NMR, and 13
C
NMR spectra. Thus, the 1H NMR spectrum of each isolated product 3a–e exhibited a vinylic proton signal at about
6.95–7.37 ppm, which is in agreement with the (Z) configuration [13] for the vinyl moiety (Scheme 1).
Presumably, the zwitterionic intermediate formed from the acetylenic ester and isoquinoline, is protonated by 1 to
furnish intermediate 4, which is attacked by the anion of the SH-acidic 1 in a Michael fashion to produce 7. This
intermediate is converted to 8 via a proton-shift reaction, and produces 3 by elimination of isoquinoline (Scheme 2).
Under similar conditions, the reaction of alkyl propiolates 9a and b with 1a led to alkyl 3-(benzo[d]oxazol-2-
ylthio)acrylates 10 and 11 (Scheme 3).
To extend our knowledge of this reaction, we performed the reaction between dialkyl acetylenedicarboxylates and
2-mercaptobenzimidazol in the presence of isoquinoline. These reactions led to alkyl 4-oxo-4H-[1,3]thiazino[3,2-
a]benzimidazole-2-carboxylates 12a and b (Fig. 1).
CO2R
1
CO2R
X
N
+
2
N
N
S
N
+
CO2R
CO2R
4
6
5
S
S
_
CO2R
CO2R
Isoquinoline
3
N
N
N
N
X
X
CO2R
CO2R
8
7
Scheme 2.

8
I. Yavari et al. / Chinese Chemical Letters 23 (2012) 5–8
CO2R
Isoquinoline
N
N
N
O
15 mol%
CO2R
S
+
S
SH
+
2-4 h, rt
O
O
10-(Z)
11-(E)
CO2R
R
Me
Et
1a
Yield (%)
50
52
9a
9b
R
Me
Et
R
Me
Et
Yield (%)
40
32
10a
10b
11a
11b
Scheme 3.
O
S
R
N
O
N
12a: R = Me
12b: R = Et
O
Fig. 1. Strctures of compounds 12.
In summary, the reaction between dialkyl acetylenedicarboxylates and 2-mercaptobenzoxazole in the presence of
isoquinoline as catalyst provides a simple one-pot synthesis of dialkyl (Z)-2-[2-thioxo-1,3-benzoxazole-3(2H)-yl]-2-
butendioates of potential synthetic and pharmaceutical interest. In the same way, alkyl propiolates and 2-
mercaptobenzoxazole led to alkyl 3-(benzo[d]oxazol-2-ylthio)acrylates.
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