A novel synthesis of 2-alkylthiobenzothiazoles and 2-alkylthiobenzoxazoles

Article abstract of DOI:10.1080/10426507.2011.636229

3H-Benzothiazole-2-thione and 3H-benzoxazole-2-thione were selectively S-alkylated by use of O-alkylisoureas as the alkylating reagents. The reactions could be performed under mild reaction conditions in short reaction times, and high yields were obtained using O-primary-alkylisoureas, whereas low yields were obtained with sec-and tert-alkylisoureas.

Full text of DOI:10.1080/10426507.2011.636229

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A Novel Synthesis of 2-
Alkylthiobenzothiazoles and 2-
Alkylthiobenzoxazoles
Yanfei Yu a , Zhengning Li a b & Lan Jiang a
a College of Environmental and Chemical Engineering, Dalian
University, Dalian, China
b Liaoning Key Laboratory of Bioorganic Chemistry, Dalian University,
Dalian, China
Version of record first published: 27 Mar 2012.
To cite this article: Yanfei Yu , Zhengning Li & Lan Jiang (2012): A Novel Synthesis of 2-
Alkylthiobenzothiazoles and 2-Alkylthiobenzoxazoles, Phosphorus, Sulfur, and Silicon and the Related
Elements, 187:5, 632-640
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Phosphorus, Sulfur, and Silicon, 187:632–640, 2012
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2011.636229
A NOVEL SYNTHESIS OF
2-ALKYLTHIOBENZOTHIAZOLES
AND 2-ALKYLTHIOBENZOXAZOLES
Yanfei Yu,1 Zhengning Li,1,2 and Lan Jiang1
1College of Environmental and Chemical Engineering, Dalian University,
Dalian, China
2Liaoning Key Laboratory of Bioorganic Chemistry, Dalian University,
Dalian, China
GRAPHICAL ABSTRACT
H
N
O
N
R
N
X
i
R
Pr
Dioxane
r.t.
10--30 min
+
S
S
HN
i
Pr
X
(X = S, O)
30%--99%
Abstract 3H-Benzothiazole-2-thione and 3H-benzoxazole-2-thione were selectively S-
alkylated by use of O-alkylisoureas as the alkylating reagents. The reactions could be
performed under mild reaction conditions in short reaction times, and high yields were
obtained using O-primary-alkylisoureas, whereas low yields were obtained with sec- and
tert-alkylisoureas.
Keywords Synthesis; 2-alkylthiobenzothiazole; 2-alkylthiobenzoxazole; O-alkylisourea;
alkylation
INTRODUCTION
2-Alkylthiobenzothiazoles and 2-alkylthiobenzoxazoles are of synthetic, biological,
and pharmaceutical importance.1 They are used as intermediates in the formation of C C
double bonds via S-oxidation, condensation, and Julia olefination that has been applied to
the synthesis of substituted exoglycals2 and amphidinolide.3 They have also been exten-
sively utilized in medicinal chemistry4 due to their diverse biological activities.5 Synthetic
methods toward them are mainly based upon the Williamson reaction of 3H-benzothiazole-
2-thione and 3H-benzoxazole-2-thione, with alkyl halides or their analogues in alkaline
media.2,6,7 Palladium(0)-catalyzed8 and copper-catalyzed9 regioselective allylation (N-
versus S-allylation) of the azole-2-thiones provide another method for this kind of thioethers.
Nevertheless, these methods suffered from using toxic organic halides, long reaction times,
Received 4 September 2011; accepted 24 October 2011.
This work was supported by the National Natural Science Foundation of China (No. 20972020).
Address correspondence to Zhengning Li, College of Environmental and Chemical Engineering, Dalian
University, Dalian 116622, China. E-mail: znli@dl.cn
632

SYNTHESIS OF 2-ALKYLTHIOBENZOTHIAZOLES AND 2-ALKYLTHIOBENZOXAZOLES 633
or expensive reagents, which limited their large-scale application. Therefore, the explo-
ration of efficient, low-cost methods is still a subject of research. In recent years, alcohols
were used as alkylating reagent in the presence of Mitsunobu reagents (PPh3/DEAD or
DIAD)3,10 or PPh3-I2 for the S-alkylation. The utilization of imino ether as the alky-
11
lating reagent to 3H-benzothiazole-2-thione has also been reported, yielding S-alkylation
products in 63%–85% yields.4
Partly due to the easy approach of O-alkylisoureas,12 they have been extensively used
as alkylating reagents in esterification of carboxylic acids13 in high yields and used, even
less commonly, in O-alkylation of phenol12b and S-alkylation of benzenethiol or alkanethi-
ols.14,15 Very recently, O-benzylisourea was used in Lewis-acid-promoted benzylation of
alcohols.16
We are interested in the novel reactions of carbodiimide (CDI) and O-alkyl
isourea.17,18 Herein, we wish to report that O-alkylisoureas can act as alkylating reagents
in the selective S-alkylation of 3H-benzothiazole-2-thione and 3H-benzoxazole-2-thione.
This provides an efficient method for the synthesis of 2-alkylthiobenzothiazoles and
2-alkylthiobenzoxazoles under mild conditions.
RESULTS AND DISCUSSION
The fact that thioethers are produced by the reaction between O-alkylisoureas
and alkanethiols15 indicates that alkanethiols exhibit enough acidity to activate O-
alkylisoureas. Therefore, we supposed that the thiol form of 3H-benzothiazole-2-thione
and 3H-benzoxazole-2-thione (Scheme 1) might also have the ability to react with
O-alkylisoureas. Even though that 2 kinds of alkylated products, the S- and N-alkylation
products, could be formed theoretically because there are two potential nucleophilic sites,
the stronger nucleophilic sulfur atom and the relatively weaker nitrogen atom, in the
deprotonated oxazole-2-thione, it was expected that the S-alkylation product would be the
predominant one in the product mixture.
H
H
N
X
N
S
S
X
(X = S, O)
Thione form
Thiol form
Scheme 1
With this in mind, we started our experiments on the reaction between O-alkylisourea
and 3H-benzothiazole-2-thione. Initially, dichloromethane was used as the solvent, and
O-alkyl-, O-allyl-, and O-benzylisoureas were selected as the alkylating reagents. 3H-
Benzothiazole-2-thione could be converted completely in short reaction time at room
temperature, yielding S-alkyl products as the predominant ones besides N-alkyl derivatives
as minor byproducts. The phenomenon is similar to those reported in the literature where
both S- and N-alkylation products are formed in favor of the S-alkylation.19 The structure
of the S-alkyl derivatives could be easily deduced from the characteristic 13C NMR signal
around δ = 167 ppm and were confirmed by comparison the NMR data with those reported
in the literature. In TLC, the S-alkylation product has a larger Rf value than its N-alkylation

634
Y. YU ET AL.
Table 1 The reaction of 3H-benzothiazole-2-thione with O-ethylisourea in different solvents
Entry
Solvent
Time (min)
Ratio of S-/N-alkylation
Yield of 4b (%)
1
2
3
4
5
6
7
DCM
5
5
90:10
90:10
96:4
88:12
94:6
60
46
87
74
75
86
90
DCM (0 ◦C)
THF
10
10
30
30
5
DMF
Acetonitrile
Toluene
96:4
96:4
1,4-dioxane
Reaction conditions: 3H-benzothiazole-2-thione 0.35 mmol, O-ethylisourea 1.02 eq., solvent 0.3 mL, room
temperature except noted.
counterpart. Therefore, separation of the S-alkyl from the N-alkyl products was easily
achieved. Then, the solvents were optimized using the reaction of O-ethylisourea with
3H-benzothiazole-2-thione as the model reaction. The results are listed in Table 1. High
yields of S-alkyl products with small amounts of N-alkyl product were obtained in 1,4-
dioxane (entry 7). Accordingly, the S-alkylation reactions of 3H-benzothiazole-2-thione
with different O-alkylisoureas were performed in 1,4-dioxane. The results are summarized
in Table 2. High selectivity and good yields were obtained for S-alkylation with primary-
alkyl- and allylisoureas (entries 1–8). The fast completion of the reaction is comparable to
that under microwave irradiation, and the yields for primary alkylation are comparable to
those using alkyl halides.7 Whereas the use of secondary and tertiary alkylisoureas gave ca.
90% and 60% selectivity to the S-alkylation products and medium to low S-alkylation yields,
even though excess of isoureas were used in some cases. The low yield for tert-butylisourea
is associated with the competitive elimination of tertiary alkyl isourea.20
H
N
O
N
R
N
X
Pri
R
+
S
S
HN
Pri
X
_
1, 2
3a 3k
4, 5
1: X = S;
2: X = O
3g: R = CH3(CH2)3CH(CH2CH3)CH2
4: X = S;
5: X = O
3a: R = CH3
3b: R= CH3CH2
3c: R = CH3CH2CH2
3d: R = PhCH2
3h: R = CH2=CHCH2
3i: R = CH3(CH2)5(CH3)CH
3j: R = (CH3)2CH
3k: R = (CH3)3C
3e: R = Ph(CH2)2CH2
3f: R = CH3(CH2)6CH2
Scheme 2
The S-alkylation reaction was extended to 3H-benzoxazole-2-thione, and similar
results, as shown in Table 3, were obtained.
The successful S-alkylation with of O-primary-alkylisoureas prompted us to carry out
the reaction by use of unpurified O-alkyliosureas. When equal molar amounts of alcohol,
N,Nꢁ-diisopropylcarbodiimide (DIC) and the 2-thione were stirred together, incomplete
transformation of substrate was observed, and both S-alkylation and N-alkylation products

SYNTHESIS OF 2-ALKYLTHIOBENZOTHIAZOLES AND 2-ALKYLTHIOBENZOXAZOLES 635
Table 2 The reaction of O-alkylisoureas with 3H-benzothiazole-2-thione (Scheme 2, X = S)
Entry
isourea
Time (min)
Ratio of S-/N-alkylationa
Yield of 4 (%)b
1
2
3
4
5
6
7
8
9
3a
3b
3c
3d
3e
5
5
10
5
20
30
30
5
30
30
20
99:1
96:4
95:5
96:4
95:5
97:3
92:8
98:2
90:10
88:12
60:40
94 (4a)
90 (4b)
92 (4c)
94 (4d)
94 (4e)
72 (4f)
65 (4g)
98 (4h)
35 (4i)
30 (4j)
56 (4k)
3f
3g
3h
3ic
3jc
3kc
10
11
Reaction conditions: 3H-benzothiazole-2-thione 0.35 mmol, O-alkylisourea 1.02–1.10 eq., 1,4-dioxane 0.3 mL,
room temperature. aBy GC analysis; bisolated yield; c2 eq. isourea.
were generated. Pleasantly, the reaction of preformed, unpurified O-alkylisourea generated
from alcohol and equivalent amounts of DIC in the presence of copper(I) chloride gave
reasonable selectivity and yield of S-alkylation products. Thus, a mixture of alcohol and
DIC and copper(I) chloride was stirred for 2–10 h until the disappearance of DIC or
alcohol, and then 3H-benzoxazole-2-thione or 3H-benzothiazole-2-thione and 1,4-dioxane
were added to carry out the reactions at room temperature for 10–40 min with TLC
tracing. Generally, good to excellent yields were achieved for the primary alkylation, and
low yields for the secondary and tertiary ones. The results are given in Table 4. In one
experiment using 30 mmol of 3H-Benzothiazole-2-thione, 4d could be produced in 90%
yield.
Table 3 The reaction of O-alkylisoureas with 3H-benzoxazole-2-thione (Scheme 2, X = O)
Entry
isourea
Time (min)
Ratio of S-/N-alkylationa
Yield of 5 (%)b
1
2
3
4
5
6
7
8
9
3a
3b
3c
3d
3e
5
5
10
5
10
30
30
5
30
30
20
98:2
97:3
95:5
97:3
91:9
96 (5a)
87 (5b)
85 (5c)
95 (5d)
92 (5e)
68 (5f)
62 (5g)
98 (5h)
36 (5i)
40 (5j)
55 (5k)
3f
95:5
3g
3h
3ic
3jc
3kc
89:11
98: 2
87:13
90:10
72:28
10
11
Reaction conditions are the same as those in Table 2 expect that 3H-benzoxazole-2-thione was used. aBy GC
analysis; bisolated yield; c2 eq. isourea.

636
Y. YU ET AL.
Table 4 One-pot synthesis of 2-alkylthiobenzothia(oxa)zole from CDI, alcohol, and 3H-benzothia(oxa)zole-2-
thione
Entry
Alcohol
Timea (min)
Yield of 4b (%)
Yield of 5b(%)
1
2
3
4
5
6
7
8
9
CH3OH
CH3CH2OH
n-C3H7OH
PhCH2OH
PhCH2OH
Ph(CH2)3OH
CH3(CH2)7OH
CH3(CH2)3CH(Et)CH2OH
CH2=CHCH2OH
CH3(CH2)5CH(CH3)OH
(CH3)2CHOH
(CH3)3COH
10
10
10
10
10
20
40
40
10
40
30
30
91 (4a)
70 (4b)
55 (4c)
86 (4d)
88c (4d)
75 (4e)
65 (4f)
71 (4g)
91 (4h)
33 (4i)
38 (4j)
23 (4k)
86 (5a)
72 (5b)
48 (5c)
98 (5d)
91c (5d)
70 (5e)
55 (5f)
70 (5g)
93 (5h)
30 (5i)
34 (5j)
28 (5k)
10
11
12
aThe reaction time for in situ formed isoureas with 3H-benzothia(oxa)zole-2-thione; bisolated yield for S-
alkylation; cDCC instead of DIC was used.
CONCLUSION
A convenient method for the S-alkylation of 3H-benzothiazole-2-thione and 3H-
benzoxazole-2-thione can be achieved by use of O-primary-alkylisoureas as the alkylating
reagents. The low toxicity, readily availability of O-alkylisoureas, the mild reaction con-
ditions and the fastness (5–30 min at room temperature) make this method synthetically
attractive.
EXPERIMENTAL
Solvents were dried with molecular sieves prior to use. O-Alkylisoureas were pre-
pared according to literature methods.12b,12c 1H NMR and 13C NMR spectra were recorded
on a Varian Mercury Plus-400 NMR Spectrometer in CDCl3 at 400 and 100 MHz, respec-
tively, unless otherwise noted. The NMR data were calibrated with TMS as the reference
for 1H NMR and CDCl3 for 13C NMR. MS spectra were recorded on an HP 6890/5973 GC-
MS spectrometer; S-/N-alkylation ratios were determined by GC analyses on a Shimadzu
GC-2010 gas chromatograph (SE-54 capillary column, 30 m × 0.32 mm × 4 µm).
Typical Procedure for the S-Alkylation of
3H-Benzothia(oxa)zole-2-thione with O-Alkylisoureas
3H-Benzothia(oxa)zole-2-thione (58 mg, 0.347 mmol) was added to the solution of
O-3-phenylpropylisourea (100 mg, 0.371 mmol) in 1,4-dioxane (0.3 mL), and the mixture
was stirred at room temperature. The progress of the reaction was monitored by TLC,
which indicated that 3H-benzothia(oxa)zole-2-thione disappeared in 5–10 min. Column
chromatographic separation (silica gel) gave the S-alkylating product 4e (93 mg, yield
94%).

SYNTHESIS OF 2-ALKYLTHIOBENZOTHIAZOLES AND 2-ALKYLTHIOBENZOXAZOLES 637
General Procedure for the Synthesis of 2-(Alkylthio)benzothia(oxa)
zoles 4 and 5 from CDI, Alcohol, and 3H-Benzothia(oxa)zole-2-thione
CuCl (5 mg, 0.05 mmol) was added to a mixture of benzyl alcohol (0.200 g, 1.85
mmol) and DIC (0.250 g, 1.82 mmol), and the mixture was stirred overnight at room
temperature until nearly complete conversion of the DIC. Then, anhydrous 1,4-dioxane
(1.0 mL) and 3H-benzothiazole-2-thione (0.240 g, 1.44 mmol) were added, and the mixture
was continually stirred until the disappearance of 3H-benzothiazole-2-thione (20 min) as
monitored by TLC. The reaction mixture was analyzed by GC to determine the ratio of
S-/N-alkylation products and then column chromatographed by EA/PE, giving the pure
2-(benzylthio)benzothiazole (4d) 0.318 g (86%).
4a: colorless solid, mp 41 ◦C–43 ◦C (Ref. 6a 45 ◦C–46◦C). 1H NMR δ: 7.86 (d, J =
8.1 Hz, 1H), 7.72 (d, J = 8.0 Hz, 1H), 7.39 (td, J = 7.7, 1.1 Hz, 1H), 7.26 (td, J = 7.7,
0.5 Hz, 1H), 2.76 (s, 3H); 13C NMR δ: 168.10, 153.39, 135.17, 126.09, 124.12, 121.40,
120.99, 15.98 ppm. The NMR data are in agreement with the literature.21 MS (EI, 70 eV),
m/z (%) 181 (100), 166 (25), 136 (40), 122 (30), 108 (80), 102 (15).
4b: colorless liquid. 1H NMR δ: 7.87 (d, J = 8.1 Hz, 1H), 7.74 (d, J = 7.9 Hz, 1H),
7.40 (td, J = 7.7, 0.5 Hz, 1H), 7.28 (td, J = 7.7, 0.4 Hz, 1H), 3.35 (q, J = 7.4 Hz, 2H), 1.48
(t, J = 7.4 Hz, 3H); 13C NMR δ: 167.15, 153.50, 135.30, 126.10, 124.23, 121.59, 121.03,
28.06, 14.71 ppm. The NMR data are in agreement with the literature.21 MS (EI, 70 eV),
m/z (%) 195 (100), 180 (30), 166 (80), 136 (16), 108 (36), 63 (15).
4c: colorless liquid. 1H NMR δ: 7.86 (d, J = 8.1 Hz, 1H), 7.74 (d, J = 7.9 Hz, 1H),
7.40 (td, J = 7.7, 1.0 Hz, 1H), 7.27 (td, J = 7.8, 0.8 Hz, 1H), 3.32 (t, J = 7.2 Hz, 2H),
1.94–1.78 (m, 2H), 1.08 (t, J = 7.4 Hz, 3H); 13C NMR δ: 167.45, 153.47, 135.27, 126.08,
124.20, 121.55, 121.00, 35.64, 22.81, 13.49 ppm. The 1H NMR data are in agreement with
the literature.1 MS (EI, 70 eV), m/z (%) 209 (60), 194 (35), 181(30), 167(100), 136 (12),
108(26), 91(8).
◦
◦
◦
◦
1
4d: colorless solid, mp 38 C–39 C (Ref. 6a 45 C–46 C). H NMR δ: 7.89 (d,
J = 8.1 Hz, 1H), 7.72 (d, J = 8.0 Hz, 1H), 7.48–7.36 (m, 3H), 7.36–7.13 (m, 4H), 4.59 (s,
2H); 13C NMR δ: 166.52, 153.26, 136.29, 135.44, 129.24, 128.81, 127.86, 126.17, 124.40,
121.67, 121.11, 37.84 ppm. The NMR data are in agreement with the literature.22 MS (EI,
70 eV), m/z (%) 257 (98), 224 (95), 166 (10), 108 (12), 91 (100), 65 (15).
4e: colorless liquid. 1H NMR δ: 7.85 (d, J = 8.1 Hz, 1H), 7.71 (d, J = 8.0 Hz, 1H),
7.43–7.33 (m, 1H), 7.33–7.13 (m, 6H), 3.32 (t, J = 7.2 Hz, 2H), 2.78 (t, J = 7.5 Hz,
2H), 2.21–2.07 (m, 2H) ppm. 13C NMR δ: 166.80, 153.24, 140.75, 135.11, 128.40, 128.37,
126.01, 125.91, 124.04, 121.38, 120.84, 34.56, 32.74, 30.67 ppm. MS (EI, 70 eV), m/z (%)
285 (25), 238 (100), 167 (60), 148 (8), 117 (11), 91 (48), 65 (11).
1
4f: colorless liquid. H NMR δ: 7.85 (d, J = 8.1 Hz, 1H), 7.69 (dd, J = 8.0, 0.5
Hz, 1H), 7.40–7.33 (m, 1H), 7.26–7.20 (m, 1H), 3.30 (t, J = 7.4 Hz, 2H), 1.83–1.73 (m,
2H), 1.48–1.39 (m, 2H), 1.36–1.19 (m, 8H), 0.87 (t, J = 6.8 Hz, 3H); 13C NMR δ: 167.59,
153.62, 135.40, 126.19, 124.29, 121.67, 121.12, 33.84, 32.07, 29.46, 29.42, 29.34, 29.07,
22.94, 14.41 ppm. MS (EI, 70 eV), m/z (%) 279 (55), 264 (1), 246 (12), 234 (17), 220 (15),
167 (100), 164 (26), 134 (17), 91 (5).
1
4g: colorless liquid. H NMR δ: 7.57 (dd, J = 7.7, 0.7 Hz, 1H), 7.42–7.37 (m,
1H), 7.24 (td, J = 7.6, 1.3 Hz, 1H), 7.19 (td, J = 7.7, 1.4 Hz, 1H), 3.42–3.20 (m, 2H),
1.76–1.73 (pent, J = 6.2 Hz, 1H), 1.51–1.44 (m, 2H), 1.42–1.38 (m, 2H), 1.35–1.23 (m,
4H), 0.99–0.83 (m, 6H); 13C NMR δ: 168.05, 153.56, 135.36, 126.19, 124.27, 121.60,
121.11, 39.37, 37.99, 32.70, 29.02, 25.98, 23.17, 14.35, 11.12 ppm. MS (EI, 70 eV),

638
Y. YU ET AL.
m/z (%) 279 (25), 264 (1), 250 (8), 222 (7), 180 (13), 167 (100), 136 (8), 122 (6),
91 (2).
4h: colorless liquid. 1H NMR δ: 7.86 (d, J = 8.1 Hz, 1H), 7.73 (d, J = 7.9 Hz, 1H),
7.39 (td, J = 7.8, 1.1 Hz, 1H), 7.27 (td, J = 7.6, 1.0 Hz, 1H), 6.00 (ddt, J = 16.9, 10.0,
6.9 Hz, 1H), 5.36 (dd, J = 16.9, 1.2 Hz, 1H), 5.18 (dd, J = 10.0, 0.7 Hz, 1H), 3.97 (d, J =
6.9 Hz, 2H); 13C NMR δ: 166.27, 153.28, 135.40, 132.39, 126.14, 124.36, 121.67, 121.06,
119.27, 36.34 ppm. MS (EI, 70 eV), m/z (%) 207 (70), 192 (100), 162 (30), 149 (25), 122
(45).
1
4i: colorless liquid. H NMR δ: 7.87 (d, J = 8.2 Hz, 1H), 7.73 (dd, J = 8.0, 0.5
Hz, 1H), 7.45–7.35 (m, 1H), 7.32–7.23 (m, 1H), 3.97 (h, J = 6.8 Hz, 1H), 1.84–1.75 (m,
1H), 1.74–1.64 (m, 1H), 1.51–1.39 (m, 4H), 1.35–1.25 (m, 7H), 0.88 (t, J = 6.8 Hz, 3H);
13C NMR δ: 166.82, 153.52, 135.39, 126.02, 124.24, 121.65, 120.97, 44.57, 36.80, 31.79,
29.16, 27.03, 22.70, 21.61, 14.20 ppm. MS (EI, 70 eV), m/z (%) 279 (38), 264 (1), 250 (5),
236 (3), 208 (4), 195 (23), 167 (100), 134 (2), 108 (22), 91 (5).
4j: colorless liquid. 1H NMR δ: 7.88 (d, J = 8.1 Hz, 1H), 7.75 (d, J = 7.9 Hz, 1H),
7.44–7.37 (m, 1H), 7.32–7.24 (m, 1H), 4.08 (sept, J = 6.8 Hz, 1H), 1.50 (d, J = 6.8 Hz,
6H). The NMR data are in agreement with the literature.1 13C NMR δ: 166.58, 153.54,
135.41, 126.09, 124.34, 121.73, 121.04, 39.59, 23.43 ppm. MS (EI, 70 eV), m/z (%) 209
(32), 167 (100), 152 (2), 122 (5), 108 (12), 43 (6).
4k: colorless liquid. 1H NMR δ: 7.98 (d, J = 8.1 Hz, 1H), 7.78 (d, J = 8.0 Hz, 1H),
1
7.44 (t, J = 7.7 Hz, 1H), 7.34 (t, J = 7.6 Hz, 1H), 1.60 (s, 9H). The H NMR data are
in agreement with the literature.1,23 13C NMR δ: 163.79, 153.83, 136.50, 126.11, 124.96,
122.69, 120.98, 50.79, 31.15 ppm. MS (EI, 70 eV), m/z (%) 223 (25), 167 (100), 122 (15),
108 (30), 57 (48), 41 (25).
5a: colorless liquid. 1H NMR δ: 7.59 (dd, J = 7.7, 0.8 Hz, 1H), 7.43–7.39 (m, 1H),
7.26 (td, J = 7.6, 1.3 Hz, 1H), 7.21 (td, J = 7.7, 1.4 Hz, 1H), 2.74 (s, 3H); 13C NMR δ:
165.79, 152.04, 142.01, 124.33, 123.86, 118.37, 109.91, 14.60 ppm. The NMR data are in
agreement with the literature.6h MS (EI, 70 eV), m/z (%) 165 (100), 150 (60), 132 (99), 122
(98), 104 (10).
5b: colorless liquid. 1H NMR (500 MHz, CDCl3) δ: 7.60 (dd, J = 7.6, 1.4 Hz, 1H),
7.43 (dd, J = 7.5, 1.0 Hz, 1H), 7.28 (td, J = 7.7, 1.3 Hz, 1H), 7.25–7.21 (m, 1H), 3.32 (t,
J = 7.4 Hz, 2H), 1.51 (t, J = 7.4 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ: 165.17, 151.97,
142.20, 124.38, 123.92, 118.52, 109.97, 26.79, 14.93 ppm. MS (EI, 70 eV), m/z (%) 179
(96), 164 (20), 151 (100), 122 (60), 91 (45), 63 (30).
1
5c: colorless liquid. H NMR δ: 7.64–7.56 (m, 1H), 7.47–7.39 (m, 1H), 7.33–7.16
(m, 2H), 3.29 (t, J = 7.2 Hz, 2H), 1.96–1.79 (m, 2H), 1.09 (t, J = 7.4 Hz, 3H); 13C NMR
δ: 165.35, 151.90, 142.11, 124.33, 123.87, 118.44, 109.93, 34.29, 22.86, 13.40 ppm. The
data are in agreement with the literature.24 MS (EI, 70 eV), m/z (%) 193 (55), 178 (10), 165
(12), 151 (100), 122 (34), 91 (37), 63 (20).
5d: colorless solid, mp 48 ◦C–49 ◦C (Ref. 6a 45 ◦C–46◦C). 1H NMR δ: 7.62 (dd, J =
8.4, 1.3 Hz 1H), 7.45 (td, J = 7.0, 1.0 Hz, 3H), 7.33 (t, J = 7.2 Hz, 2H), 7.30 (dd, J =
6.3, 1.4 Hz, 1H), 7.27–7.21 (m, 2H), 4.57 (s, 2H); 13C NMR δ: 164.67, 152.03, 142.07,
135.99, 129.22, 128.91, 128.06, 124.45, 124.09, 118.63, 110.05, 36.73 ppm. The data are
in agreement with those reported in the literature.25 MS (EI, 70 eV), m/z (%) 241 (98), 208
(40), 150 (5), 122 (10), 91(100), 65 (11).
1
5e: colorless liquid. H NMR δ: 7.63–7.56 (m, 1H), 7.46–7.38 (m, 1H), 7.34–7.26
(m, 3H), 7.28–7.20 (m, 4H), 3.31 (t, J = 7.2 Hz, 2H), 2.81 (t, J = 7.3 Hz, 2H), 2.21–2.14
(m, 2H); 13C NMR δ: 165.03, 151.95, 142.11, 140.90, 128.62, 126.27, 124.38, 123.93,

SYNTHESIS OF 2-ALKYLTHIOBENZOTHIAZOLES AND 2-ALKYLTHIOBENZOXAZOLES 639
118.51, 109.96, 34.66, 31.68, 30.92 ppm. MS (EI, 70 eV), m/z (%) 269 (25), 222 (100),
209 (5), 151 (50), 117 (45), 91 (75), 65 (13).
1
5f: colorless liquid. H NMR δ: 7.62–7.54 (m, 1H), 7.44–7.38 (m, 1H), 7.26 (td,
J = 7.6, 1.3 Hz, 1H), 7.23–7.18 (m, 1H), 3.30 (t, J = 7.4 Hz, 2H), 1.90–1.73 (m, 2H),
1.48–1.43 (m, 2H), 1.37–1.18 (m, 8H), 0.88 (t, J = 6.8 Hz, 3H); 13C NMR δ: 165.32,
151.84, 142.08, 124.23, 123.75, 118.37, 109.82, 32.34, 31.85, 29.29, 29.21, 29.11, 28.75,
22.72, 14.18 ppm. MS (EI, 70 eV), m/z (%) 263 (35), 248 (1), 234 (2), 220(15), 193 (30),
151 (100), 134 (9), 106 (2), 91 (14).
5g: colorless liquid. 1H NMR δ: 7.59 (dd, J = 7.7, 0.7 Hz, 1H), 7.44–7.40 (m, 1H),
7.26 (td, J = 7.6, 1.3 Hz, 1H), 7.22 (td, J = 7.7, 1.4 Hz, 1H), 3.50–3.26 (m, 2H), 1.75 (sept,
J = 6.2 Hz, 1H), 1.55–1.46 (m, 2H), 1.45–1.40 (m, 2H), 1.37–1.25 (m, 4H), 1.01–0.71 (m,
6H); 13C NMR δ: 165.71, 151.87, 142.10, 124.27, 123.78, 118.39, 109.85, 39.04, 36.58,
32.40, 28.80, 25.69, 23.01, 14.19, 10.91 ppm. MS (EI, 70 eV), m/z (%) 263 (10), 248 (1),
234 (3), 207 (5), 192 (12), 151 (100), 122 (8), 106 (1), 91 (3).
5h: colorless liquid. 1H NMR δ: 7.60 (dd, J = 8.3, 0.5 Hz, 1H), 7.42 (dd, J = 7.8,
0.8 Hz, 1H), 7.27 (td, J = 7.6, 1.3 Hz, 1H), 7.22 (td, J = 7.7, 1.3 Hz, 1H), 6.03 (ddt, J =
16.9, 10.0, 6.9 Hz, 1H), 5.39 (dd, J = 16.9, 1.2 Hz, 1H), 5.20 (d, J = 10.0 Hz, 1H), 3.95
(d, J = 6.9 Hz, 2H); 13C NMR δ: 164.36, 151.93, 141.98, 132.19, 124.34, 123.96, 119.33,
118.53, 109.93, 34.95 ppm. The data are in agreement with those reported in the literature.5
MS (EI, 70 eV), m/z (%) 191 (79), 176 (100), 158 (58), 150 (74), 122 (85), 96 (9), 78 (11),
63 (16).
5i: colorless liquid. 1H NMR δ: 7.64–7.57 (m, 1H), 7.44 (d, J = 7.6 Hz, 1H), 7.31–7.26
(m, 1H), 7.26–7.19 (m, 1H), 3.94 (h, J = 6.8 Hz, 1H), 1.93–1.64 (m, 2H), 1.59–1.42 (m,
5H), 1.41–1.17 (m, 6H), 0.88 (t, J = 6.7 Hz, 3H); 13C NMR δ: 165.08, 151.74, 142.19,
124.30, 123.88, 118.52, 109.93, 43.57, 36.70, 31.81, 29.15, 27.01, 22.73, 21.89, 14.22 ppm.
MS (EI, 70 eV), m/z (%) 263 (34), 248 (1), 234 (2), 220 (5), 174 (4), 151 (100), 134 (2),
106 (2), 91 (15).
1
5j: colorless liquid. H NMR δ: 7.61–7.55 (m, 1H), 7.40 (d, J = 7.4 Hz, 1H),
7.28–7.22 (m, 1H), 7.22–7.17 (m, 1H), 4.22–3.91 (m, 1H), 1.50 (d, J = 6.8 Hz, 6H) ppm.
The 1H NMR data are in agreement with those reported in the literature.24 MS (EI, 70 eV),
m/z (%) 193 (25), 151 (100), 122 (10), 106 (2), 91 (10), 43 (6).
5k: colorless liquid. 1H NMR δ: 7.65 (dd, J = 6.5, 2.2 Hz, 1H), 7.46 (dd, J = 6.6,
2.3 Hz, 1H), 7.35–7.23 (m, 2H), 1.65 (s, 9H); 13C NMR δ: 163.37, 151.37, 142.07, 124.37,
124.29, 119.10, 110.02, 49.78, 31.04 ppm. MS (EI, 70 eV), m/z (%) 207 (60), 192 (100),
180(20), 165 (53), 149 (19),122 (40), 108 (67), 41 (35).
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