TBAI-Catalyzed Reaction between N-Tosylhydrazones and Sulfur: A Procedure toward 1,2,3-Thiadiazole

Article abstract of DOI:10.1021/acs.joc.5b02280

A TBAI-catalyzed reaction between N-tosyl hydrazone and sulfur was developed, leading to 1,2,3-thiadiazoles in moderate to good yields. It represents a facile and practical procedure to access thiadiazole under metal-free conditions. This procedure serves

Full text of DOI:10.1021/acs.joc.5b02280

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Note
TBAI-Catalyzed Reaction between N-Tosylhydrazones
and Sulfur: a Procedure toward 1,2,3-Thiadiazole
Yan Jiang, Jin-Tao Yu, Jiang Cheng, and Jiangfei Chen
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.5b02280 • Publication Date (Web): 16 Dec 2015
Downloaded from http://pubs.acs.org on December 17, 2015
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TBAIꢀCatalyzed Reaction between N-Tosylhydrazones and Sulfur: a
Procedure toward 1,2,3ꢀThiadiazole
Jiangfei Chen, Yan Jiang, JinꢀTao Yu, and Jiang Cheng*
School of Petrochemical Engineering, Jiangsu Key Laboratory of Advanced Catalytic Materials & Technology, Jiangꢀ
su Province Key Laboratory of Fine Petrochemical Engineering, Changzhou University, Changzhou 213164, P. R.
China.
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Email: jiangcheng@cczu.edu.cn
RECEIVED DATE (to be automatically inserted after your manuscript is accepted if required according to the
journal that you are submitting your paper to)
ABSTRACT
A TBAIꢀcatalyzed reaction between Nꢀtosyl hydrazone and sulfur was developed, leading to 1,2,3ꢀthiadiazole in
moderate to good yields. It represents a facile and practical procedure to access thiadiazole under metalꢀfree condition.
This procedure serves as an improvement for HurdꢀMori reaction.
1
1
,2,3ꢀThiadiazoles show broad pharmacological properties, such as platelet aggregation inhibitor, neuroprotective
2
3
4ꢀ5
6ꢀ7
regents, antitumor activities, antiviral activities, and inhibitors of Hsp90 chaperone. Moreover, they serve as inꢀ
8ꢀ12
termediates in organic synthesis.
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Scheme 1 Reactions toward 1,2,3ꢀthiadiazole.
The diazotization of αꢀamino ketones followed by the reaction with Lawesson's reagent delivered 1,2,3ꢀthiadiazoles
14
(Scheme 1, eq 1). Meanwhile, the HurdꢀMori reaction was a powerful procedure to access such a structure (Scheme 1,
15ꢀ17
eq 2).
thiadiazoles (Scheme 1, eq 3).
access 1,2,3ꢀthiadiazoles (Scheme 1, eq 3).
with tosyl azide leading to 4,5ꢀdisubstituted 1,2,3ꢀthiadiazoles. The reaction of lithium (trimethylsilyl)diazomethane
Pechmann and Nold described the reaction of diazomethane with phenyl isothiocyanate leading to 1,2,3ꢀ
1
8ꢀ19
1,3ꢀDipolar cycloaddition of diazoalkanes to thiocarbonyl compounds allowed to
2
0,21
Recently, Singh reported [3+2] cycloaddition of αꢀenolicdithioesters
2
2
[
TMSC(Li)=N ] with thiocarbonyl compounds has proved to be a convenient method for the preparation of 5ꢀ
2
23
substituted 1,2,3ꢀthiadiazoles (Scheme 1, eq 4). However, the diazo compounds and azide are explosive, while SOCl ,
2
SCl and S Cl react violently with water. Thus, the development of a safe methodology would be beneficial to organic
2
2
2
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chemistry. Herein, we wish to report a TBAIꢀcatalyzed reaction between Nꢀtosylhydrazones and element sulfur leadꢀ
13
ing to 4ꢀaryl 1,2,3ꢀthiadiazoles. Sulfur powder is cheap, safe and abundant in nature. Moreover, the rigorous extruꢀ
sion of moisture is not required in this procedure.
a
Table 1. Screening the Optimized Reaction Conditions.
b
entry
1
catalyst
I2
oxidant
K S O
solvent
DMAC
yield (%)
61
2
2
8
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KI
K S O
DMAC
DMAC
DMAC
DMAC
DMAC
57
78
69
<5
41
2
2
8
8
8
8
8
8
1
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NH4I
K S O
2 2
NIS
K S O
2 2
PIDA
CuI
K S O
2 2
K S O
2
2
c
d
e
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
ꢀꢀ
K S O
DMAC 84(62) (60) (82)
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NH S O
8
DMAC
DMAC
DMAC
DMAC
PhCH3
63
4
2
f
9
K S O
49
2
2
8
10
DDQ
H O
NR
NR
NR
NR
NR
NR
NR
NR
1
1
1
1
1
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4
2
2
K S O
2
2
8
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K S O
CH CN
2
2
3
K S O
dioxane
DMAC
DMAC
DMAC
2
2
g
1
5
6
K S O
2 2
h
i
1
ꢀꢀ
K S O
17
2
2
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a
o
Reaction conditions: 1a (0.1 mmol), catalyst (20 mol%), oxidant (0.2 mmol), 2a (0.5 mmol) and solvent (1.5 mL) at 100 C under air for
2 h, sealed tube. Isolated yield. DMF. 2a (0.3 mmol). 2a (0.4 mmol). 2a (Na S, 0.5mmol) Without 2a. Without K S O .
Without TBAI. TBAI = tetraꢀbutylammonium iodide; PIDA = iodobenzene diacetate; DMAC = dimethylacetamide.
b
c
d
e
f
g
h
i
2
2
2
8
o
Initially, we tested the combination of acetophenone tosylhydrazone, sulfur, I and K S O in DMAC under 100 C
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2
2
8
for 12 h. To our delight, the annulation product was isolated in 61% yield (Table 1, entry 1). KI, NH I, and CuI all
4
worked to some extent with the yields ranging from 41ꢀ78% (Table 1, entries 2ꢀ4, and 6). However, PIDA failed to
work (Table 1, entry 5). The yield further increased to 84% by employing TBAI (Table 1, entry 7). Replacing DMAC
with DMF decreased the reaction efficiency (62%, Table 1, entry 7). Increasing the loading of sulfur had no positive
effect on the reaction efficiency (Table 1, entry 7). Other oxidants, such as DDQ and H O , resulted in no reaction
2
2
(
Table 1, entries 10 and 11). The reaction did not work under toluene, acetonitrile and dioxane (Table 1, entries 12ꢀ14).
Sulfur took part in the reaction as confirmed by the blank experiment (Table 1, entry 15). No reaction took place in the
absence of TBAI or K S O (Table 1, entries 16 and 17). Notably, the procedure was applicable to 10 mmol scale, and
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the product 3a was isolated in 77% yield (Scheme 2).
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Scheme 2
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After the establishment of the optimal reaction condition, the scope of Nꢀtosylhyrazone was studied, as shown in
Figure 1. As expected, the procedure was applicable for substrates with both electron donating and withdrawing groups
in the phenyl ring, providing 4ꢀaryl 1,2,3ꢀthiadiazoles in moderate to good yields. The procedure tolerated the funcꢀ
tional groups, such as bromo, trifluoromethyl, cyano, methoxy carbonyl, chloro and acetamino well. Notably, this proꢀ
cedure provided a rapid access to 4ꢀheteroaryl analogues, such as 3h, 3k, 3l and 3r. Particularly, 4ꢀalkenyl 1,2,3ꢀ
thiadiazole 3q was isolated in 44% yield. However, the aliphatic analogues of NꢀTs hydrazone did not take placeunder
the procedure. The application of selenium and tellurium powder in the procedure could not provide the target product
(Figure 1).
a
Figure 1. Scope of NꢀTs Hydrazone.
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N
N
NNHTs
TBAI (20 mol %)
K S O (2 equiv)
+
S
S
1
2
3
4
5
6
7
8
9
Ar
2
2
8
Ar
1
2
3
N
N
N
N
N
N
S
S
S
MeO
3
3
a, 84%
3b, 94%
3c, 98%
N N
N
S
N
N
N
S
S
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F
Br
F3C
d, 73%
3e, 66%
3f, 76%
N
N
N
N
N
N
S
S
S
MeO
NC
O
3
g, 97%
3h, 51%
3i, 90%
N
N
N
N
N
N
S
S
S
N
S
3j, 81%
3k, 60%
3l, 52%
N S
N
N
N
S
N
OMeN
S
O
OMe
3o, 77%
3m, 71%
3n, 84%
N
N
N
N
N
N
S
S
S
O
O
N
3
p, 81%
3q, 44%
3r, 58%
N
N
N
S
N
N
N
S
S
O
N
Cl
MeO
H
3s, 86%
3t, 76%
3u, 89%
a
o
Reaction conditions: 1 (0.1 mmol), 2 (sublimed sulfur, 0.5 mmol), TBAI (20 mol%), K S O (0.2 mmol) and DMAC (1.5 mL) at 100 C
2
2
8
under air for 2 h, sealed tube.
To further get some insights into the mechanism, more experiments were conducted. Firstly, 2,2,4,4ꢀtetramethylꢀ1ꢀ
piperidinyloxy (TEMPO, 1 equiv), galvinoxyl free radical and 2,6ꢀdiꢀtertꢀbutylꢀpꢀcresol (BHT, 1 equiv) were added to
25
the standard procedure and none of them was inhibited (Scheme 3, eq 1). The potential intermediates, such as 4, 5, 6
and 7 all ran smoothly under the standard procedure with comparable yields (Scheme 3, eqs 2ꢀ4). Moreover, the reacꢀ
tion efficiency of 4ꢀ7 was hardly affected by radical inhibitor, which was consistent with the result in eq 1. However,
disulfide was not formed by the reaction of αꢀiodo acetophenone and sulfur under the standard procedure (Scheme 3,
eq 5). These results ruled out the possibility of 7 as the intermediate.
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Scheme 3 Preliminary Mechanism Study
Based on these experimental results, a proposed mechanism was outlined in Scheme 4. Firstly, in the presence of
ꢀ
+
K S O , I was oxidized to I . Then, the αꢀiodation of acetophenone tosylhydrazone took place to form intermediate 4.
2
2
8
ꢀ
Subsequently, the elimination of HI in 4 provided intermediate 5, along with the releasing of I , which was oxidized to
I to fulfill the catalytic cycle. Secondly, the addition of S to 5 produces intermediate 6, which transforms to intermeꢀ
2
8
diate 7. After that, the intraꢀmolecular nucleophilic attack took place to form intermediate 8. Finally, the elimination of
ꢀ
Ts and S delivered 1,2,3ꢀthiadiazoles.
7
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Scheme 4 A Tentative Mechanism
In conclusion, we have developed a TBAIꢀcatalyzed direct annulation of acetophenone tosylhydrazone and sufur
powder, leading to 1,2,3ꢀthiadiazoles in moderate to excellent yields. This procedure avoids the employment of hazard
starting materials. Furthermore, the rigorous extrusion of moisture is not required in this procedure. Thus, it represents
a practical pathway to access such a structure as a key progress in HurdꢀMori reaction.
EXPERIMENTAL SECTION
1. General Considerations
1
13
Chemicals were used as received without special purification unless stated otherwise. H and C NMR spectra were
1
3
recorded at ambient temperature on a 300 or 400 MHz NMR spectrometer (75 or 100 MHz for C NMR). NMR reꢀ
sults were reported in δ units, parts per million (ppm), and were referenced to CDCl3 ( 7.26 or 77.0 ppm) as the interꢀ
δ
nal standard. The coupling constants J are given in Hz. Melting points were taken on an electrothermal melting point
apparatus and without correction. IR spectra were recorded on a spectrometer using KBr discs.
Experimental Procedure: A sealed tube was charged with N‑ tosylhydrazone (0.1 mmol), sulfur (0.5 mmol),
o
TBAI (0.02 mmol), K S O (0.2 mmol), DMAC (1.5 mL). The mixture was stirring under air at 100 C for 2 h. The
2
2
8
mixture was washed by water and extracted by ethyl acetate then concentrated in vacuum and the residue was purified
by preparative TLC on GF254 (petroleum/ethyl acetate) to afford the desired product.
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-phenyl-1,2,3-thiadiazole (3a) : TLC on GF254 (ethyl acetate: petroleum, 1:20) give the product (13.6 mg, 84%
o
1
yield) as a white solid. mp 75ꢀ77 C. H NMR (CDCl , 400 MHz): δ 8.65 (s, 1H), 8.05 (d, J = 7.2 Hz, 2H), 7.53ꢀ7.43
3
13
(
m, 3H); C NMR (CDCl , 100 MHz): δ 162.9, 130.8, 130.0, 129.4, 129.2, 127.4.
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-(p-tolyl)-1,2,3-thiadiazole (3b) : TLC on GF254 (ethyl acetate: petroleum, 1:20) give the product (16.0 mg,
o
1
9
4% yield) as a white solid. mp 73ꢀ75 C. H NMR (CDCl , 400 MHz): δ 8.59 (s, 1H), 7.94 (d, J = 8.0 Hz, 2H), 7.31
3
13
(
d, J = 8.0 Hz, 2H), 2.42 (s, 3H); C NMR (CDCl , 100 MHz): δ 163.0, 139.5, 129.9, 129.3, 128.1, 127.3, 21.4.
3
1
7
4
-(4-methoxyphenyl)-1,2,3-thiadiazole (3c) : TLC on GF254 (ethyl acetate: petroleum, 1:20) give the product
o
1
(
17.6 mg, 98% yield) as a white solid. mp 89ꢀ93 C. H NMR (CDCl , 400 MHz): δ 8.52 (s, 1H), 7.98 (d, J = 8.8 Hz,
3
13
2
H), 7.03 (d, 8.8Hz, 2H), 3.87 (s, 1H); C NMR (CDCl , 100 MHz): δ 162.7, 160.5, 128.7, 128.4, 123.5, 114.5, 55.4.
3
17
4
-(4-fluorophenyl)-1,2,3-thiadiazole (3d) : TLC on GF254 (ethyl acetate: petroleum, 1:20) give the product (12.5
o
1
mg, 73% yield) as a white solid. mp 185ꢀ188 C. H NMR (CDCl , 400 MHz): δ 8.61 (s, 1H), 8.05ꢀ8.01 (m, 2H), 7.22ꢀ
3
13
7
.18 (m, 2H); C NMR (CDCl , 100 MHz): δ 163.4 (d, J = 248.0 Hz), 161.8, 129.7, 129.2 (d, JCꢀF = 8.3 Hz), 127.0,
3
CꢀF
1
16.2 (d, JCꢀF = 21.8 Hz).
17
4
-(4-bromophenyl)-1,2,3-thiadiazole (3e) : TLC on GF254 (ethyl acetate: petroleum, 1:20) give the product (13.7
o
1
mg, 66% yield) as a white solid. mp 150ꢀ152 C. H NMR (CDCl , 400 MHz): δ 8.65 (s, 1H), 7.92 (d, J = 8.8 Hz, 2H),
3
13
7
.63 (d, J = 8.4 Hz, 2H); C NMR (CDCl , 100 MHz): δ 161.7，132.3, 130.3, 129.7, 128.8, 123.6.
3
4
-(4-(trifluoromethyl)phenyl)-1,2,3-thiadiazole (3f): TLC on GF254 (ethyl acetate: petroleum, 1:20) give the
o
1
product (15.2 mg, 76% yield) as a white solid. mp 70ꢀ72 C. H NMR (CDCl , 400 MHz): δ 8.77 (s, 1H), 8.18 (d, J =
3
13
8
1
.0 Hz, 2H), 7.78 (d, J = 8.4 Hz 2H); C NMR (CDCl , 100 MHz): δ 161.3, 134.0, 131.4 (q, J = 32.6 Hz), 131.4,
3 CꢀF
+
26.2 (q, JCꢀF = 3.8 Hz), 125.2 (q, JCꢀF = 270.4 Hz). MS (EI): 230 (M ); HRMS (ESIꢀTOF) m/z calcd for C H F N S
9
5
3
2
ꢀ
ꢀ1
(M+COOH) 275.0103, found 275.0108 IR (KBr) ν 3090, 2923, 2852, 1637, 1592, 1542, 1465, 1327, 1121 cm .
2
6
4-(1,2,3-thiadiazol-4-yl)benzonitrile (3g)
: TLC on GF254 (ethyl acetate: petroleum, 1:20) give the product (17.1
1
mg, 97% yield) as a white solid. H NMR (CDCl , 400 MHz): δ 8.82 (s, 1H), 8.18 (d, J = 8.4 Hz, 2H), 7.80 (d, J = 8.4
3
13
Hz, 2H); C NMR (CDCl , 100 MHz): δ 160.8, 134.8, 133.0, 132.1, 127.8, 118.3, 112.9.
3
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-(furan-2-yl)-1,2,3-thiadiazole (3h) : TLC on GF254 (ethyl acetate: petroleum, 1:20) give the product (7.8 mg,
1
2
3
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8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
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4
4
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5
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5
1% yield) as a yellow solid. H NMR (CDCl , 400 MHz): δ 8.59 (s, 1H), 7.56 (s, 1H), 7.15 (d, J = 7.2 Hz, 1H), 6.59ꢀ
3
13
6
.57 (m, 1H); C NMR (CDCl , 100 MHz): δ 154.7, 146.6, 143.4, 128.4, 111.9, 109.5.
3
4
-(3-methoxyphenyl)-1,2,3-thiadiazole (3i): TLC on GF254 (ethyl acetate: petroleum, 1:30) give the product (34.8
1
mg, 90% yield) as a pale yellow liquid. H NMR (CDCl , 400 MHz): δ 8.64 (s, 1H), 7.65ꢀ7.64 (m, 1H), 7.56 (d, 7.6 Hz,
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
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2
3
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5
6
7
8
9
0
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2
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4
5
6
7
8
9
0
13
1
H ), 7.40 (t, J = 8.0 Hz, 1H), 6.98 (m, 1H), 3.88 (s, 3H); C NMR (CDCl , 100 MHz): δ 162.7, 160.2, 132.0, 130.2,
3
+
+
1
30.2, 119.7, 115.3, 112.7, 55.4. MS (EI): 192 (M ); HRMS (ESIꢀTOF) m/z calcd for C H N OS (M+H) 193.0432,
9
8
2
ꢀ1
found 193.0430. IR (KBr) ν 3110, 3003, 2933, 1603, 1589, 1514, 1464, 1437, 1245, 1158, 1035 cm .
17
4
-(naphthalen-2-yl)-1,2,3-thiadiazole (3j) : TLC on GF254 (ethyl acetate: petroleum, 1:20) give the product (15.4
o
1
mg, 81% yield) as a white solid. mp 202ꢀ206 C. H NMR (CDCl , 400 MHz): δ 8.76 (s, 1H), 8.60 (s, 1H), 8.10 (d, J =
3
1
3
1
0.0 Hz, 1H), 7.99ꢀ7.97 (m, 2H), 7.89ꢀ7.88 (m, 1H), 7.56ꢀ7.54 (m, 2H); C NMR (CDCl , 100 MHz): δ 162.9, 145.6,
3
1
33.7, 133.5, 130.1, 129.0, 128.5, 128.1, 127.8, 126.9, 126.8, 124.7.
17
4
-(thiophen-2-yl)-1,2,3-thiadiazole (3k) : TLC on GF254 (ethyl acetate: petroleum, 1:30) give the product (10.1
o
1
mg, 60% yield) as a white solid. mp 70ꢀ73 C. H NMR (CDCl , 400 MHz): δ 8.51 (s, 1H), 7.65ꢀ7.64 (m, 1H), 7.43ꢀ
3
13
7
.42 (m, 1H), 7.16ꢀ7.14 (m, 1H); C NMR (CDCl , 100 MHz): δ 157.3, 133.1, 128.4, 127.9, 127.0, 126.4.
3
17
4
-(pyridin-2-yl)-1,2,3-thiadiazole (3l) : TLC on GF254 (ethyl acetate: petroleum, 1:10) give the product (8.5 mg,
o
1
5
2% yield) as a white solid. mp 158ꢀ160 C. H NMR (CDCl , 400 MHz): δ 9.23 (s, 1H), 8.68 (d, 4.8Hz 1H), 8.46 (d,
3
1
3
J = 8.0 Hz, 1H), 7.89ꢀ7.85 (m, 1H), 7.36ꢀ7.33 (m, 1H); C NMR (CDCl , 100 MHz): δ 163.3, 149.9, 149.8, 137.4,
3
1
33.9, 123.9, 122.5.
2
8
4
-(2-methoxyphenyl)-1,2,3-thiadiazole (3m) : TLC on GF254 (ethyl acetate: petroleum, 1:20) give the product
o
1
(
12.7 mg, 71% yield) as a yellow solid. mp 94ꢀ97 C. H NMR (CDCl , 400 MHz): δ 9.06 (s, 1H), 8.52ꢀ8.49 (m, 1H),
3
1
3
7
.44ꢀ7.40 (m, 1H), 7.16ꢀ7.12 (m, 1H), 7.06 (d, J = 8.0 Hz, 1H), 3.97 (s, 3H); C NMR (CDCl , 100 MHz): δ 158.5,
3
1
56.3, 133.3, 130.4, 130.3, 121.2, 111.2, 55.5.
1
7
4
-(naphthalen-1-yl)-1,2,3-thiadiazole (3n) : TLC on GF254 (ethyl acetate: petroleum, 1:20) give the product
o
1
(
16.0 mg, 84% yield) as a white solid. mp 198ꢀ200 C. H NMR (CDCl , 400 MHz): δ 8.67 (s, 1H), 8.10ꢀ8.08 (m, 1H),
3
1
3
7.94ꢀ7.80 (m, 2H), 7.77ꢀ7.75 (m, 1H), 7.60ꢀ7.52 (m, 1H); C NMR (CDCl , 75 MHz): δ 161.9, 134.2, 133.8, 131.4,
3
129.9, 128.5, 128.4, 127.1, 126.3, 125.2, 125.1.
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methyl 4-(1,2,3-thiadiazol-4-yl)benzoate (3o): TLC on GF254 (ethyl acetate: petroleum, 1:20) give the product
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
o
1
(
15.1 mg, 77% yield) as a yellow solid. mp 144ꢀ146 C. H NMR (CDCl , 400 MHz): δ 8.77 (s, 1H), 8.18ꢀ8.11 (m,
3
13
4
H), 3.95 (s, 3H); C NMR (CDCl , 100 MHz): δ 166.5, 161.7, 134.8, 131.4, 130.8, 130.4, 127.2, 52.3. MS (EI): 220
3
+
+
(
M ); HRMS (ESIꢀTOF) m/z calcd for C H N O S (M+H) 221.0380, found 221.0379. IR (KBr) ν 3093, 2963, 1729,
10 8 2 2
ꢀ1
1
611, 1455, 1439, 1414 cm .
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
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2
3
4
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6
7
8
9
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2
3
4
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7
8
9
0
4
-(benzo[d][1,3]dioxol-5-yl)-1,2,3-thiadiazole (3p): TLC on GF254 (ethyl acetate: petroleum, 1:20) give the prodꢀ
o
1
uct (15.0 mg, 81% yield) as a yellow solid. mp 124ꢀ126 C. H NMR (CDCl , 400 MHz): δ 8.50 (s, 1H), 7.55ꢀ7.52 (m,
3
13
2
H), 6.92 (d, J = 8.0 Hz 1H), 6.03 (s, 2H); C NMR (CDCl , 100 MHz): δ 162.6, 148.6, 148.3, 128.8, 124.9, 121.5,
3
+
+
108.9, 107.8, 101.5. MS (EI): 206 (M ); HRMS (ESIꢀTOF) m/z calcd for C H N O S (M+H) 207.0222, found
9
6
2
2
ꢀ1
2
07.0223. IR (KBr) ν 3091, 2922, 2360, 1629, 1608, 1522, 1464, 1445, 1244, 1039 cm .
29
(E)-4-styryl-1,2,3-thiadiazole (3q) : TLC on GF254 (ethyl acetate: petroleum, 1:20) give the product (7.7 mg,
o
1
4
4% yield) as a yellow solid. mp 81ꢀ83 C. H NMR (CDCl , 400 MHz): δ 8.38 (s, 1H), 7.71 (d, J = 16.4 Hz, 1H),
3
1
3
7.57 (d, J = 7.6 Hz, 2H), 7.43 (d, J = 8.4 Hz, 1H), 7.39 (d, J = 7.2 Hz, 2H), 7.33 (t, J = 7.4 Hz, 1H); C NMR (CDCl ,
3
1
00 MHz): δ 161.2, 136.1, 134.7, 130.2, 128.8, 128.7, 126.9, 117.1.
30
4-(pyridin-4-yl)-1,2,3-thiadiazole (3r) : TLC on GF254 (ethyl acetate: petroleum, 1:10) give the product (9.0 mg,
o
1
5
8% yield) as a white solid. mp 162ꢀ164 C. H NMR (CDCl , 400 MHz): δ 9.23 (s, 1H), 8.79 (s, 1H), 8.68ꢀ8.67 (m,
3
1
3
1H), 8.40 (d, J = 8.0 Hz, 1H), 7.47ꢀ7.44 (m, 1H); C NMR (CDCl , 100 MHz): δ 159.7, 150.5, 148.3, 134.7, 131.0,
3
1
26.9, 124.0.
17
4-(4-chlorophenyl)-1,2,3-thiadiazole (3s) : TLC on GF254 (ethyl acetate: petroleum, 1:20) give the product (15.6
o
1
mg, 86% yield) as a white solid. mp 136ꢀ138 C. H NMR (CDCl , 400 MHz): δ 8.64 (s, 1H), 7.80ꢀ7.79 (m, 2H), 7.49ꢀ
3
13
7
.46 (m, 2H); C NMR (CDCl , 100 MHz): δ 161.7, 135.4, 130.2, 129.4, 129.2, 128.6.
3
N-(4-(1,2,3-thiadiazol-4-yl)phenyl)acetamide (3t): Flash column chromatography on a silica gel (ethyl acetate:
o
1
petroleum, 1:2) give the product (14.8 mg, 76% yield) as a yellow solid. mp 216ꢀ218 C. H NMR (CDCl , 400 MHz):
3
1
3
δ 10.14 (s, 1H), 9.48 (s, 1H), 8.07 (d, J = 8.4 Hz, 2H), 7.76 (d, J = 8.4 Hz, 2H), 2.09 (s, 3H); C NMR (CDCl , 100
3
+
MHz): δ 168.7, 161. 8, 140.3, 132.0, 127.7, 125.4, 119.4, 24.2. MS (EI): 219 (M ); HRMS (ESIꢀTOF) m/z calcd for
+
C H N OS (M+H) 220.0540, found 220.0539. IR (KBr) ν 3315, 3107, 2961, 1728, 1671, 1604, 1545, 1464, 1411,
1
0
10
3
ꢀ1
1
260 cm
4
-(6-methoxynaphthalen-2-yl)-1,2,3-thiadiazole (3u): TLC on GF254 (ethyl acetate: petroleum, 1:20) give the
o
1
product (18.4 mg, 89% yield) as a yellow solid. mp 150ꢀ151 C. H NMR (CDCl , 400 MHz): δ 8.68 (s, 1H), 8.50 (s,
3
1
3
1
1
H), 8.07ꢀ8.05 (m, 1H), 7.86ꢀ7.82 (m, 2H), 7.22ꢀ7.17 (m, 2H), 3.95 (s, 3H); C NMR (CDCl , 100 MHz): δ 169.1,
3
+
58. 5, 135.0, 130.0, 129.4, 128.9, 127.7, 126.7, 126.0, 125.3, 119.7, 105.8, 55.4. MS (EI): 242 (M ); HRMS (ESIꢀ
+
TOF) m/z calcd for C H N OS (M+H) 243.0588, found 243.0587. IR (KBr) ν 3083, 2922, 1630, 1606, 1503, 1461,
13 11
2
ꢀ1
1
393, 1263, 1212, 1029 cm .
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ACKNOWLEDGMENT
The Journal of Organic Chemistry
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We thank the National Natural Science Foundation of China (nos. 21272028, 21572025 and 21202013), “Innovation &
Entrepreneurship Talents” Introduction Plan of Jiangsu Province, the Key University Science Research Project of
Jiangsu Province (15KJA150001), Qing Lan Project of Jiangsu Province, and Jiangsu Key Laboratory of Advanced
Catalytic Materials &Technology (BM2012110) for financial support.
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Supporting Information:
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Research of mechanism, H and C NMR spectra of compounds 3a-3u. This material is available free of charge via
the Internet at http://pubs.acs.org.
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13) Liu, H.; Jiang, X.ꢀF. Chem.–Asian J. 2013, 8, 2546.
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,2,3ꢀtriazoles, where 4 and 6 were believed to be intermediates. See: Cai, Z.ꢀJ.; Lu, X.ꢀM.; Zi, Y.; Yang, C.;
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