Addition of Diazo Compounds ipso -C-H Bond to Carbon Disulfide: Synthesis of 1,2,3-Thiadiazoles under Mild Conditions

Article abstract of DOI:10.1021/acs.joc.8b00383

We describe here an operationally simple and straightforward synthesis method for a series of diverse 4,5-disubstituted 1,2,3-thiadiazoles via the nucleophilic addition of α-diazo carbonyl compounds to carbon disulfide. This method features using abundant and inexpensive carbon disulfide under mild reaction conditions.

Full text of DOI:10.1021/acs.joc.8b00383

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Addition of Diazo Compounds ipso-C#H bond to Carbon
Disulfide: Synthesis of 1,2,3-Thiadiazoles Under Mild Conditions
Lei Zhang, Beiqi Sun, Qianyi Liu, and Fanyang Mo
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b00383 • Publication Date (Web): 19 Mar 2018
Downloaded from http://pubs.acs.org on March 19, 2018
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The Journal of Organic Chemistry
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Addition of Diazo Compounds ipso-C‒H bond to Carbon Disulfide:
Synthesis of 1,2,3-Thiadiazoles Under Mild Conditions
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Lei Zhang, Beiqi Sun, Qianyi Liu and Fanyang Mo*
†Department of Energy and Resources Engineering, College of Engineering, Peking University, Beijing 100871, China.
Supporting Information Placeholder
ABSTRACT: We describe here an operationally simple and straightforward synthesis method for a series of diverse 4,5ꢀ
disubstituted 1,2,3ꢀthiadiazoles via the nucleophilic addition of αꢀdiazo carbonyl compounds to carbon disulfide. This method feaꢀ
tures
using
abundant
and
inexpensive
carbon
disulfide
with
mild
reaction
conditions.
1,2,3ꢀthiadiazoles1 are versatile heterocycles present in various
pharmaceutical molecules.2 Due to their biological activities,
many derivatives of 1,2,3ꢀthiadiazole are important in indusꢀ
try, medicine and agriculture (Scheme 1A).3 To date, the
known methods for synthesizing 1,2,3ꢀthiadiazoles can be
summarized as shown in Scheme 1B: a) cyclization of hydraꢀ
zones with thionyl chloride (HurdꢀMori synthesis);4 b) treatꢀ
ment of αꢀdiazo carbonyl compounds with Lawesson’s reaꢀ
gent (Wolff synthesis);5 c) addition of diazomethane (Pechꢀ
mann synthesis)6 or lithium (trimethylsilyl)diazomethane7 to
Recently, we have reported transitionꢀmetalꢀfree diazo comꢀ
pounds ipsoꢀC‒H bond addition to carbon dioxide (CO2) under
very mild reaction conditions with the diazo group retained.10
The resulting αꢀdiazo carboxylate intermediate is readily conꢀ
verted to esters and amides in a oneꢀpot manner (Scheme 2A).
CO2 is a greenhouse gas that has been attracting much attenꢀ
tion as an inexpensive, nontoxic, nonflammable, renewable
and abundant C1 building block for organic synthesis.11
Meanwhile, carbon disulfide (CS2), an analogue of CO2, has
long been used as a sulfur source for a variety of useful chemꢀ
icals for agricultural, medicinal, and pharmaceutical applicaꢀ
tions.12 As an extension of our previous work, here we report
on diazo compound ipsoꢀC‒H bond addition to CS2 for the
synthesis of 1,2,3ꢀthiadiazoles under mild conditions (Scheme
2B).
thiocarbonyl
compounds; d)
diazotization
of
αꢀ
enolicdithioesters;8 and e) oxidative cyclization of Nꢀ
tosylhydrazones and sulfur.9 Although these techniques are
frequently used, the synthesis of 1,2,3ꢀthiadiazoles remains an
active research area.
Scheme 2. Diazo Compound ipsoꢀC‒H Bond Addition to
CO2 and CS2
Scheme 1. Introduction of 1,2,3ꢀThiadiazoles
To probe the feasibility of the nucleophilic addition of the
diazo group to CS2, we initiated our studies with ethyl diazoꢀ
acetate (EDA) 1a and benzyl bromide (BnBr) 2a as the standꢀ
ard substrates. Various organic and inorganic bases were exꢀ
amined in the initial studies. As shown in Table 1, with
Cs2CO3 as the base, the desired product ethyl 5ꢀ(benzylthio)ꢀ
1,2,3ꢀthiadiazoleꢀ4ꢀcarboxylate 3a was obtained with 38%
NMR yield (entry 1). CsF and KOtBu turned out to be less
effective in this transformation (entries 2 and 3) and organic
bases, such as DBU and Et3N, were inactive (entries 4 and 5).
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This suggested that bases with proper basicity might be a key
Page 2 of 5
product. Meanwhile, as a good electrophile, carbon disulfide
has ready reactivity with a variety of nucleophiles, ranging
from carbonꢀcentered nucleophiles (e. g. Grignard reagents) to
oxygenꢀcentered nucleophiles (e. g. alkoxy) and amines.12c
Based on the above, we proposed that our reaction mechanism
1
2
3
4
5
6
7
8
issue for the desired transformation. Indeed, the yield was
slightly improved with the use of KOH as the base (entry 6).
3a was then obtained with 73% yield by switching the solvent
from MeCN to DMF (entry 7). Other solvents, such as DMSO,
THF and 1,4ꢀdioxane, were less efficient (entries 8ꢀ10). Finalꢀ
ly, an improved yield (81%) was obtained by using 2.0 equivaꢀ
lent of CS2 (entry 11). The yield was not further improved by
increasing the equivalency of CS2 to 5.0 (entry 12). However,
the product 3a was not very stable during handling and the
isolated yield diminished to about 10% compared with the
NMR yield.
is also
tion/cyclization process (Scheme 3).
a
normal deprotonationꢀnucleophilic addiꢀ
Table 2. Substrates Scopea
SR
9
EWG
H
KOH, DMF
50 oC, 12 h
EWG
+
CS2
+
RBr
S
N
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
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31
32
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60
N2
N
3
2
1
Table 1. Selected Optimization of Reaction Conditionsa
O
S
O
S
O
S
EtO
EtO
EtO
EtO
S
N
S
S
N
N
N
N
N
3a, 69%
3b, 68%
3c, 59%
entry
1
base
Cs2CO3
CsF
KOtBu
DBU
Et3N
solvent
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
DMF
equivalency of CS2
yield (%)b
O
S
S
O
S
O
S
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
2.0
5.0
38
17
Br EtO
F EtO
S
S
2
N
N
N
N
N
N
3d, 64%
3e, 56%
3f, 50%
3
20
4
trace
n. d.
41
O
O
S
5
S
6
KOH
KOH
KOH
KOH
KOH
KOH
KOH
N
N
XRD of 3g
7
73
3g, 70%
8
DMSO
THF
36
O
S
S
O
S
S
9
12
10
11
12
1,4ꢀDioxane
DMF
8
N
N
N
N
81 (69c )
3h, 64%
3i, 62%
DMF
78
O
S
O
S
S
a
Reaction conditions: EDA (0.5 mmol), BnBr (1.5 equiv), base (1.2
o
N
N
equiv), solvent (2 mL), reaction time 12 h, temperature 50 C, sealed. n.
S
d., not detected. Yields were determined by 1H NMR spectroscopy with
b
N
N
O
N
N
1,1,2,2ꢀtetrachloroethane used as internal standard. c Isolated yield.
3j, 47%
3k, 39%
a Reaction conditions: diazo compound (0.5 mmol), RBr (1.5 equiv), KOH
(1.2 equiv), solvent (2 mL), reaction time 12 h, temperature 50 oC, sealed.
After obtaining the optimal yield for 3a, we next conducted
substrate scope studies with the results shown in Table 2. Varꢀ
ious benzyl bromides were evaluated with various substituent
groups for this reaction. Both paraꢀ and orthoꢀ substituents
(3bꢀ3e) on benzyl bromides were tolerated, giving good
yields. Additionally, allyl bromide (3f) was also a good reaꢀ
gent to facilitate the construction of 1,2,3ꢀthiadiazoles. To
further demonstrate the expansibility of this methodology,
various αꢀdiazo carbonyl compounds were synthesized and
tested using this transformation. In general, all these types of
diazo substrates were suitable for the reaction with the prodꢀ
ucts obtained with moderate to good yields. Menthyl diazoaceꢀ
tate was converted to 1,2,3ꢀthiadiazole (3g) with 70% yield.
XRD data was obtained for 3g. Furthermore, αꢀdiazo alkyl
ketones (3h and 3i) also worked well, while αꢀdiazo amides
(3j and 3k) gave relatively low yields.
Scheme 3. Proposed Reaction Pathway
In summary, we have developed an operationally simple
method for the synthesis of 4,5ꢀdisubstituted 1,2,3ꢀthiadiazoles
via the nucleophilic addition of αꢀdiazo carbonyl compounds
to carbon disulfide. This method can be applied as an alternaꢀ
tive to traditional synthesis methods of 1,2,3ꢀthiadiazoles with
carbon disulfide as the C1 building block with mild reaction
conditions.
Compared with the known methods shown in Scheme 1B,
our synthetic strategy is more close to the catalog c: addition
of diazo compounds to C=S double bond. In reference 7, Aoꢀ
yama suggested a nucleophilic addition/cyclization mechaꢀ
nism for the conversion of lithium (trimethylsiꢀ
lyl)diazomethane and carbon disulfide to the 1,2,3ꢀthiadiazole
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The Journal of Organic Chemistry
1
ether: EtOAc = 100:1 ~ 50:1 as eluent; H NMR (400 MHz,
CDCl3) δ 7.55 – 7.48 (m, 2H), 7.32 (d, J = 8.5 Hz, 2H), 4.51
(q, J = 7.1 Hz, 2H), 4.21 (s, 2H), 1.46 (t, J = 7.1 Hz, 3H). 13C
NMR (100 MHz, CDCl3) δ 163.8, 160.7, 146.5, 132.7, 132.3,
130.7, 122.8, 62.2, 41.6, 14.3. IR (film) 2984, 1730, 1700,
1487, 1440, 1310, 1271, 1210, 1066, 1012, 842, 780. HRMS
EXPERIMENTAL SECTION
1
2
3
4
5
6
7
8
General Information. All the solvents were purchased
from ENERGY CHEMICAL and kept dry by molecular sieves.
The products were purified by column chromatography on
silica gel (300ꢀ400 mesh, from Qingdao, China). NMR spectra
were measured on a Bruker ARX400 (1H at 400 MHz, 13C at
100 MHz, 19F at 377 MHz) magnetic resonance spectrometer.
The chemical shifts (δ) are reported as ppm using tetrameꢀ
thylsilane as the internal standard (s = singlet, d = doublet, t =
triplet, q = quartet, dd = doublet of doublets, dt = doublet of
triplets, m = multiplet) while the coupling constants (J) were
reported in Hertz (Hz). Infrared spectra were recorded on a
Thermal Fisher Nicolet iS50 Fourier transform spectrometer
(FTꢀIR) and were reported as wave numbers (cmꢀ1). The
HRMS data was obtained on a VG ZABꢀHS mass spectromeꢀ
ter and a Brucker Apex IV FTMS spectrometer. The diazo
starting materials were synthesized in the lab. For details, see
Supporting Information.
(ESI): calcd for C12H12BrN2O2S2 [M+H]+: 358.9518; found:
+
358.9512.
Ethyl
5-((4-fluorobenzyl)thio)-1,2,3-thiadiazole-4-
carboxylate (3e). White solid, yield 56% (84 mg); mp = 63ꢀ
9
64 °C; Rf = 0.20 (petroleum ether: EtOAc = 10:1); petroleum
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60
1
ether: EtOAc = 100:1 ~ 50:1 as eluent; H NMR (400 MHz,
CDCl3) δ 7.42 (dd, J = 8.5, 5.2 Hz, 2H), 7.06 (t, J = 8.5 Hz,
2H), 4.51 (q, J = 7.1 Hz, 2H), 4.24 (s, 2H), 1.46 (t, J = 7.1 Hz,
3H). 13C NMR (100 MHz, CDCl3) δ 164.0 (d, J = 2.1 Hz),
161.5, 160.8, 146.4, 130.9 (d, J = 8.4 Hz), 129.4 (d, J = 3.3
Hz), 116.2, 116.0, 62.2, 41.6, 14.3. 19F NMR (377 MHz,
CDCl3) δ ꢀ112.5 – ꢀ112.6 (m). IR (film) 2984, 1730, 1700,
1508, 1439, 1310, 1271, 1210, 1159, 1064, 1017, 842, 780.
General procedure for the synthesis of 1,2,3ꢀthiadiazoles.
In a glove box, charge a 4 mL vial equipped with a stir bar
with potassium hydroxide (0.6 mmol, 1.2 equiv), dimethyl
formamide (2 mL), the diazo compound (0.5 mmol), carbon
disulfide (1.0 mmol, 2.0 equiv), bromide (0.75 mmol, 1.5
equiv) in succession. Then, seal the vial and stir the mixture at
50 °C for 12 h. Then, wash the reaction mixture with 20 mL
ethyl acetate and water (3×20 mL). Separate the organic layer
and dry over Na2SO4. After removal of the solvent, purify the
residue by column chromatography (silica gel) to afford the
desired product.
+
HRMS (ESI): calcd for C12H12FN2O2S2 [M+H]+: 299.0319;
found: 299.0311.
Ethyl 5-(allylthio)-1,2,3-thiadiazole-4-carboxylate (3f). Yelꢀ
low oil, yield 50% (58 mg); Rf = 0.25 (petroleum ether:
EtOAc = 10:1); petroleum ether: EtOAc = 100:1 ~ 50:1 as
1
eluent; H NMR (400 MHz, CDCl3) δ 5.90 (m, 1H), 5.50 (dd,
J = 17.0, 0.7 Hz, 1H), 5.38 (d, J = 10.1 Hz, 1H), 4.52 (q, J =
7.1 Hz, 2H), 3.71 (d, J = 6.7 H z, 2H), 1.47 (t, J = 7.1 Hz, 3H).
13C NMR (100 MHz, CDCl3) δ 164.3, 160.8, 146.7, 129.9,
121.7, 62.1, 40.6, 14.4. IR (film) 2984, 1730, 1701, 1438,
1307, 1271, 1207, 1063, 1020, 930, 842. HRMS (ESI): calcd
for C8H11N2O2S2+ [M+H]+: 231.0256; found: 231.0254.
(1S,2R,5S)-2-Isopropyl-5-methylcyclohexyl 5-(benzylthio)-
1,2,3-thiadiazole-4-carboxylate (3g). White solid, yield 70%
(136 mg); mp = 102ꢀ103 °C; Rf = 0.30 (petroleum ether:
EtOAc = 20:1); petroleum ether: EtOAc = 100:1 ~ 50:1 as
Ethyl 5-(benzylthio)-1,2,3-thiadiazole-4-carboxylate(3a).13
Yellowishꢀgreen solid, yield 78% (110 mg); mp = 83ꢀ84 °C;
Rf = 0.25 (petroleum ether: EtOAc = 10:1); petroleum ether:
1
EtOAc = 100:1 ~ 50:1 as eluent; H NMR (400 MHz, CDCl3)
δ 7.47 – 7.30 (m, 5H), 4.51 (q, J = 7.1 Hz, 2H), 4.26 (s, 2H),
1.46 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 164.4,
160.8, 146.4, 133.6, 129.14, 129.08, 128.6, 62.1, 42.3, 14.4.
1
eluent; H NMR (400 MHz, CDCl3) δ 7.50 – 7.29 (m, 5H),
5.08 – 5.01 (m, 1H), 4.25 (s, 2H), 2.23 – 2.11 (m, 1H), 2.07ꢀ
2.00 (m, 1H), 1.80 – 1.48 (m, 4H), 1.23 (dd, J = 23.2, 12.0 Hz,
1H), 1.18ꢀ1.07 (m, 1H), 0.92 (dd, J = 10.8, 6.8 Hz, 6H), 0.80
(d, J = 7.0 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 164.2,
160.4, 146.7, 133.7, 129.1, 129.1, 128.6, 76.5, 46.8, 42.4, 40.8,
34.1, 31.6, 26.2, 23.4, 22.0, 20.8, 16.3. IR (film) 2954, 2926,
2869, 1729, 1698, 1436, 1311, 1272, 1214, 1064, 980, 837,
704. HRMS (ESI): calcd for C20H27N2O2S2+ [M+H]+: 391.1508;
found: 391.1502.
Ethyl
5-((4-methylbenzyl)thio)-1,2,3-thiadiazole-4-
carboxylate (3b). White solid, yield 68% (100 mg); mp = 93ꢀ
94 °C; Rf = 0.25 (petroleum ether: EtOAc = 10:1); petroleum
ether: EtOAc = 100:1 ~ 50:1 as eluent; H NMR (400 MHz,
1
CDCl3) δ 7.32 (d, J = 8.0 Hz, 2H), 7.17 (d, J = 7.9 Hz, 2H),
4.51 (q, J = 7.1 Hz, 2H), 4.23 (s, 2H), 2.35 (s, 3H), 1.46 (t, J =
7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 164.5, 160.8,
146.4, 138.6, 130.5, 129.8, 129.0, 62.1, 42.1, 21.2, 14.4. IR
(film) 2984, 2921, 1732, 1701, 1439, 1309, 1271, 1209, 1065,
+
1-(5-(Benzylthio)-1,2,3-thiadiazol-4-yl)ethan-1-one
(3h).
1021, 842. HRMS (ESI): calcd for C13H15N2O2S2 [M+H]+:
Yellow solid, yield 64% (80 mg); mp = 100ꢀ101 °C; Rf = 0.20
(petroleum ether: EtOAc = 20:1); petroleum ether: EtOAc =
295.0569; found: 295.0563.
Ethyl
carboxylate (3c). White solid, yield 59% (87 mg); mp = 90ꢀ
91 °C; Rf = 0.25 (petroleum ether: EtOAc = 10:1); petroleum
5-((2-methylbenzyl)thio)-1,2,3-thiadiazole-4-
1
100:1 as eluent; H NMR (400 MHz, CDCl3) δ 7.39 m, 5H),
4.23 (s, 2H), 2.85 (s, 3H). 13C NMR (100 MHz, CDCl3) δ
192.4, 164.1, 154.0, 133.6, 129.2, 129.1, 128.6, 42.8, 28.8. IR
(film) 3063, 3032, 2915, 1672, 1413, 1273, 1175, 1066, 910,
790, 705, 604. HRMS (ESI): calcd for C11H11N2OS2+ [M+H]+:
251.0307; found: 251.0308.
1
ether: EtOAc = 100:1 ~ 50:1 as eluent; H NMR (400 MHz,
CDCl3) δ 7.41 – 7.15 (m, 4H), 4.50 (q, J = 7.1 Hz, 2H), 4.25 (s,
2H), 2.43 (s, 3H), 1.45 (t, J = 7.1 Hz, 3H). 13C NMR (100
MHz, CDCl3) δ 164.8, 160.8, 146.2, 137.2, 131.6, 131.0,
130.0, 129.0, 126.6, 62.1, 41.0, 19.3, 14.4. IR (film) 2980,
2932, 1730, 1701, 1439, 1310, 1272, 1209, 1065, 1020, 842,
780. HRMS (ESI): calcd for C13H15N2O2S2+ [M+H]+: 295.0569;
found: 295.0562.
1-(5-(Benzylthio)-1,2,3-thiadiazol-4-yl)-4-methylpentan-1-
one (3i). Yellow oil, yield 62% (95 mg); Rf = 0.20 (petroleum
ether: EtOAc = 40:1); petroleum ether: EtOAc = 100:1 as eluꢀ
1
ent; H NMR (400 MHz, CDCl3) δ 7.48 – 7.28 (m, 5H), 4.23
(s, 2H), 3.28 (t, J = 7.2 Hz 2H), 1.68 (m, 3H), 0.95 (d, J = 6.4
Hz, 6H). 13C NMR (100 MHz, CDCl3) δ 195.4, 164.0, 153.7,
133.7, 129.2, 129.0, 128.6, 42.7, 39.3, 32.9, 27.8, 22.4. IR
Ethyl
5-((4-bromobenzyl)thio)-1,2,3-thiadiazole-4-
carboxylate (3d). White solid, yield 64% (115 mg); mp = 93ꢀ
94 °C; Rf = 0.20 (petroleum ether: EtOAc = 10:1); petroleum
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Synthesized Via Ugi Reaction and Their Fungicidal and Antiviral
(film) 2954, 2927, 2867, 1669, 1495, 1414, 1271, 1139, 1112,
+
Activities. J. Agric. Food Chem. 2010, 58, 7846ꢀ7855; (e) Fan, R.
Z.; Wang, D.; Fan, Z. J.; Wang, S. X.; Hua, X. W.; Ji, X. T.;
Huang, Y.; Song, H. B. Synthesis, Crystal Structure, and
Biological Activity of Nꢀ((1ꢀCyclohexylꢀ1hꢀTetrazolꢀ5ꢀYl)(5ꢀ
1
2
3
4
1044, 1026, 908, 703. HRMS (ESI): calcd. C15H18N2NaOS2
[M+Na]+: 329.0753. Found: 329.0753.
(5-(Benzylthio)-1,2,3-thiadiazol-4-
yl)(morpholino)methanone (3j). White solid, yield 47% (75
Methylꢀ1,2,3ꢀThiadiazolꢀ4ꢀYl)Methyl)
ꢀ4ꢀNitrobenzenamine.
mg); mp = 96ꢀ97 °C; Rf = 0.50 (petroleum ether: EtOAc = 1:1);
5
Jiegou Huaxue 2012, 31, 803ꢀ808.
1
petroleum ether: EtOAc = 10:1 ~ 5:1 as eluent; H NMR (400
6
7
8
9
(3) (a) Yasuda, M.; Nakashita, H.; Yoshida, S. Tiadinil, a Novel
Class of Activator of Systemic Acquired Resistance, Induces
Defense Gene Expression and Disease Resistance in Tobacco. J.
Pestic. Sci. 2004, 29, 46ꢀ49; (b) Fan, Z.; Shi, Z.; Zhang, H.; Liu,
X.; Bao, L.; Ma, L.; Zuo, X.; Zheng, Q.; Mi, N. Synthesis and
Biological Activity Evaluation of 1,2,3ꢀThiadiazole Derivatives as
Potential Elicitors with Highly Systemic Acquired Resistance. J.
Agric. Food Chem. 2009, 57, 4279ꢀ4286; (c) Morzherin, Y.;
Prokhorova, P. E.; Musikhin, D. A.; Glukhareva, T. V.; Fan, Z. 2ꢀ
Hydroxypropyl Derivatives of 1,2,3ꢀThiadiazole and 1,2,3ꢀ
Triazole: Synthesis and Antifungal Activity. Pure Appl. Chem.
2011, 83, 715ꢀ722; (d) Du, Q.; Zhu, W.; Zhao, Z.; Qian, X.; Xu,
Y. Novel Benzoꢀ1,2,3ꢀThiadiazoleꢀ7ꢀCarboxylate Derivatives as
Plant Activators and the Development of Their Agricultural
Applications. J. Agric. Food Chem. 2012, 60, 346ꢀ353; (e)
Flygare, J. A.; Beresini, M.; Budha, N.; Chan, H.; Chan, I. T.;
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L.; Halladay, J.; Hymowitz, S. G.; La, H.; LoRusso, P.; Maurer,
B.; Murray, L.; Plise, E.; Quan, C.; Stephan, J.ꢀP.; Young, S. G.;
Tom, J.; Tsui, V.; Um, J.; Varfolomeev, E.; Vucic, D.; Wagner,
A. J.; Wallweber, H. J. A.; Wang, L.; Ware, J.; Wen, Z.; Wong,
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Liu, T.; Liu, M.; Qiu, W.ꢀW.; Tang, J. Synthesis and Biological
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Derivatives as Novel Inhibitors of Osteoclast Differentiation and
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Krishnaraj, T.; Muthusubramanian, S. Synthesis of Biologically
MHz, CDCl3) δ 7.45 – 7.29 (m, 5H), 4.23 (s, 2H), 4.08 (s, 2H),
3.79 (m, J = 25.0 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ
162.6, 160.2, 150.1, 134.2, 129.2, 129.0, 128.5, 67.2, 66.9,
48.0, 43.3, 42.2. IR (film) 2964, 2913, 2859, 1616, 1472,
1443, 1302, 1269, 1218, 1114, 1076, 1030, 968, 705. HRMS
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+
(ESI): calcd for C14H16N3O2S2 [M+H]+: 322.0678; found:
322.0671.
(5-(Benzylthio)-1,2,3-thiadiazol-4-yl)(pyrrolidin-1-
yl)methanone (3k). White solid, yield 39% (60 mg); mp = 124ꢀ
125 °C; Rf = 0.60 (petroleum ether: EtOAc = 1:1); petroleum
1
ether: EtOAc = 10:1 ~ 5:1 as eluent; H NMR (400 MHz,
CDCl3) δ 7.43 (m, 2H), 7.38 – 7.28 (m, 3H), 4.21 (s, 2H), 4.02
(t, J = 6.6 Hz, 2H), 3.72 (t, J = 6.7 Hz, 2H), 2.08 – 1.85 (m,
4H). 13C NMR (100 MHz, CDCl3) δ 163.0, 159.8, 150.6, 134.3,
129.2, 128.9, 128.3, 49.4, 47.2, 42.3, 26.6, 23.9. IR (film)
2970, 2875, 1610, 1468, 1454, 1374, 1256, 1079, 843, 710.
HRMS (ESI): calcd for C14H16N3OS2 [M+H]+: 306.0729;
+
found: 306.0729.
ASSOCIATED CONTENT
Supporting Information
Preparation of substrates, NMR spectra, and Xꢀray single crystal
structure of compound 3g.
AUTHOR INFORMATION
Corresponding Author
*Email: fmo@pku.edu.cn
Important
NꢀHeteroarylꢀ2ꢀ(Heteroarylthio)Acetamides.
J.
Notes
Heterocycl. Chem. 2014, 51, 1012ꢀ1019.
The authors declare no competing financial interest.
(4) Hurd, C. D.; Mori, R. I. On Acylhydrazones and 1,2,3ꢀ
Thiadiazoles. J. Am. Chem. Soc. 1955, 77, 5359ꢀ5364.
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Chem. 1904, 333, 1ꢀ21; (b) Caron, M. Convenient Preparation of
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(6) v. Pechmann, H.; Nold, A. Ueber Die Einwirkung Von
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2588ꢀ2593.
ACKNOWLEDGMENT
The project was supported by the Natural Science Foundation of
China (Grants 21502003 and 21772003). We also thank the
“1000ꢀYouth Talents Plan”, Peking University for startꢀup funds.
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