Cu-catalyzed direct C-H bond functionalization: A regioselective protocol to 5-aryl thiazolo[3,2-b]-1,2,4-triazoles

Article abstract of DOI:10.1039/c2ob27326h

An efficient, regioselective C-5 arylation of thiazolo[3,2-b]-1,2,4- triazoles catalyzed by a simple copper catalyst was developed. This arylation proceeded smoothly and tolerated a variety of functional groups (44 examples). A wide range of functionalized thiazolo[3,2-b]-1,2,4-triazole derivatives were obtained in high yields (up to 99% yield). Possible catalytic cycles of the arylation were also discussed.

Full text of DOI:10.1039/c2ob27326h

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ARTICLE TYPE
Cu-Catalyzed Direct C-H Bond Functionalization: A Regioselective
Protocol to 5-Aryl Thiazolo[3,2-b]-1,2,4-triazoles
Zengyang Xie,a Xiaojun Zhu,a Yangfan Guan,a Dunru Zhu,b Hongwen Hu,a Chen Lin,a Yi Pan,a Juli
Jiang,*a and Leyong Wanga
5
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
DOI: 10.1039/b000000x
An efficient, regioselective C-5 arylation of thiazolo[3,2-b]-1,2,4-triazoles catalyzed by the simple copper
catalyst was developed. This arylation proceeded smoothly and tolerated a variety of functional groups
(44 examples). A wide range of functionalized thiazolo[3,2-b]-1,2,4-triazole derivatives were obtained in
10 high yields (up to 99% yield). Possible catalytic cycles of the arylation was also discussed.
ve copper, as the first transition metal, has been used to promote
50 C-H bond functionalization by Hofmann14 and Zechmeister15
who had made a significant breakthrough. Although there has
been remarkable progress in copper-catalyzed C-H bond
functionalization since then,16 the applicable catalysts still remain
limited. Therefore, there is still an interesting topic to develop
55 and construct new heteroaromatic compounds by copper-
catalyzed direct C-H functionalization with simpler catalytic
systems and much milder conditions.
Introduction
Heteroaromatic compounds are widespread in various natural
products1 of enormous practical importance, ranging from
pharmaceutical agents and biological probes to electroactive
15 materials.2 As a number of representatives of this class,
thiazolo[3,2-b]-1,2,4-triazole derivatives are highly attractive
heterocyclic units because of their diverse biological activity.3-10
Examples
of
well-known
thiazolo[3,2-b]-1,2,4-triazole
Inspired by the successful results in our recent research about
the arylation of imidazo[2,1-b]thiazoles,17a we attempt the direct
60 arylation of thiazolo[3,2-b]-1,2,4-triazole to develop new
derivatives. Although from the standpoint of the “scaffold”
between thiazolo[3,2-b]-1,2,4-triazoles and imidazo[2,1-
b]thiazoles, only one atom is different, they showed a big
difference in biological activity.17b Herein, we develop a novel
65 synthetic route for 5-arylated thiazolo[3,2-b]-1,2,4-triazoles
catalyzed by copper catalyst, compatible with a variety of
functional groups. It is also the first example that the direct
arylation of thiazolo[3,2-b]-1,2,4-triazoles are accomplished so
far.
derivatives include anthelmintics,3 antimicrobial,4 medicinal
20 fungicides,5 cardiotonics, bronchodilators,6 analgesic, anti-
inflammatory,7 antipyretic,7b anticancer8 and vasodilatory drugs.9
As a classical example, in 1990s, Shibahara et al10 described the
identification and characterization of several molecules bearing
thiazolo[3,2-b]-1,2,4-triazoles as an activator of cephalosporins,
25 which had a minimum inhibitory concentration of 0.39 μg/mL
against staphylococcus aureus and could be used as a therapeutic
medicine for microbisms.
In general, the thiazolo[3,2-b]-1,2,4-triazole derivatives were
usually obtained by fusion of the heteroaromatic cycles with the
30 desired substituent at oriented position.8,11 To the best of our
knowledge, example of direct and regioselective arylation of the
thiazolo[3,2-b]-1,2,4-triazole core has not been reported thus far.
In recent years, transition-metal-catalyzed direct C-H
functionalization has received a great deal of attention,12 and a
35 wide range of metal catalysts have undergone explosive growth
in the past few years.13 Compared with those catalysts, inexpensi-
70 Results and discussion
Initially, 6-phenylthiazolo[3,2-b]-1,2,4-triazole (1a), which was
synthesized according to the literature method,18 was selected to
test the arylation. The arylation reaction was performed with 1a
and iodobenzene 2a as reactants, t-BuOLi as a base, and DMF-
75 Xylene as mixture solvent. As shown in Table 1, eleven types of
simple copper salts were tested at 120 oC for 12 h (entries 1-11).
To our surprise, the results showed not only high yields, but also
only C-5 arylated products. Among those eleven copper salts,
Cu(acac)2 afforded the highest yield (entries 10), instead of CuCl,
80 which was the best copper salt we previously reported for the
arylation of imidazo[2,1-b]thiazoles.17a Subsequently, with the
catalyst Cu(acac)2, we investigated the solvent effect for this
arylation reaction. As shown in Table 1 (entry 10, 12-17), two
good results were obtained in DMF and DMF-Xylene mixtures
aKey Laboratory of Mesoscopic Chemistry of Ministry of Education,
Center for Multimolecular Chemistry, School of Chemistry and Chemical
40 Engineering, Nanjing University, Nanjing, P.R. China, 210093. Tel &
Fax: +86(25)83597090; E-mail: jjl@nju.edu.cn
bState Key Laboratory of Material-Oriented Chemical Engineering,
College of Chemistry and Chemical Engineering, Nanjing University of
Technology, Nanjing, P.R. China, 210009
45 † Electronic Supplementary Information (ESI) available: General
experimental procedures, spectral data and copies of 1H NMR and 13C
NMR spectra. For ESI and crystallographic data in CIF or other electronic
format see DOI: 10.1039/b000000x/
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(entries 10 and 12), and the latter provided higher yield. And then
vs entries 3, 4, 9, 10). Most interestingly, this arylation was not
we explored the effects of the temperature, Cu-catalyst loading 40 sensitive to the sterically hindered factors of aryl iodides and
and base, respectively, in this arylation reaction.19 The reaction
yield decreased when the reaction temperature was reduced to
gave excellent yield (entries 11, 22, 33, 44). Furthermore, other
different substituted thiazolo[3,2-b]-1,2,4-triazoles, such as 6-(4-
bromophenyl)thiazolo[3,2-b]-1,2,4-triazole, 6-p-tolylthiazolo[3,2-
b]-1,2,4-triazoe, 6-methylthiazolo[3,2-b]-1,2,4-triazole were also
o
o
5
100 C or room temperature from 120 C, and the yield did not
o
increase when the temperature was raised to 140 C. Decreasing
the amount of addtion of Cu(acac)2 negatively affects the yield of 45 tested and afforded the corresponding products in excellent yields.
the arylated product, as does lowering the reaction temperature.
Reducing the Cu(acac)2 catalyst loading from 20 to 10 and then 5
It should be noted that the substrates 1 with electron-rich
aromatic groups gave slightly better yields than the electron-
deficient aromatic groups (entries 12-22 vs 23-33). We also found
the substrates 1 with aromatic groups gave better yields than the
10 mol % lowered the yields of product from 98% to 87% and 66%,
respectively. In the absence of the Cu catalyst, no arylated
product was found, and on the other hand, the yield could not
increase when the Cu(acac)2 loading was raised to 40 mol %.
With these above optimized arylation conditions, the effects of
15 bases were investigated. It was found that a variety of weak
inorganic bases (K2CO3, Cs2CO3 and K3PO4) were unsuitable for
the arylation ascribed to the poor yields. Compared to t-BuOLi,
we also tested other alkoxide bases, t-BuOK and t-BuONa, and
lower yields of 56% and 47% were obtained. Specially noted, no
20 arylated product was found without bases. The above
experiments demonstrated that the optimized conditions for the
C-5 arylation of thiazolo[3,2-b]-1,2,4-triazoles are: Cu(acac)2 (20
mol %) and t-BuOLi (2.0 equiv) in DMF-Xylene at 120 oC.
Moreover, PhBr and PhCl, as substitutes instead of PhI also were
25 tested, and only PhBr gave traces of C-5 arylated product under
the above optimized conditions.
50 Table 2. Scope of Cu-catalyzed Arylation of Thiazolo[3,2-b]-1,2,4-
triazolesa
Entry
R
Ar
Products Yield (%)b
1
2
3
4
5
6
7
8
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
3-CH3OC6H4
4-FC6H4
4-CF3C6H4
4-CH3C6H4
4-CH3OC6H4
4-C(CH3)3C6H4
2-C2H5C6H4
2-ClC6H4
3-FC6H4
1-naphthyl
C6H5
3-CH3OC6H4
4-FC6H4
4-CF3C6H4
4-CH3C6H4
4-CH3OC6H4
4-C(CH3)3C6H4
2-C2H5C6H4
2-ClC6H4
3-FC6H4
1-naphthyl
C6H5
3-CH3OC6H4
4-FC6H4
4-CF3C6H4
4-CH3C6H4
4-CH3OC6H4
98
94
89
85
91
93
90
96
88
82
97
95
92
86
79
90
91
94
93
85
80
95
98
96
91
88
92
93
92
95
88
83
96
90
98
83
76
93
92
99
94
87
81
93
3aa
3ab
3ac
3ad
3ae
3af
3ag
3ah
3ai
9
Table 1. Cu-catalyzed Arylation of Thiazolo[3,2-b]-1,2,4-triazolea
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
C6H5
C6H5
3aj
3ak
3ba
3bb
3bc
3bd
3be
3bf
3bg
3bh
3bi
3bj
3bk
3ca
3cb
3cc
3cd
3ce
3cf
4-BrC6H4
4-BrC6H4
4-BrC6H4
4-BrC6H4
4-BrC6H4
4-BrC6H4
4-BrC6H4
4-BrC6H4
4-BrC6H4
4-BrC6H4
4-BrC6H4
4-CH3C6H4
4-CH3C6H4
4-CH3C6H4
4-CH3C6H4
4-CH3C6H4
4-CH3C6H4
Yield(%)b
Entry
Conditions
Solvent
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
CuCl
CuBr
CuI
CuCN
CuCl2
DMF/Xylene (1:1)
DMF/Xylene (1:1)
DMF/Xylene (1:1)
DMF/Xylene (1:1)
DMF/Xylene (1:1)
DMF/Xylene (1:1)
DMF/Xylene (1:1)
DMF/Xylene (1:1)
66
85
74
70
82
62
75
71
79
98
68
93
42
51
82
43
38
CuBr2
CuCl2·2H2O
CuSO4·5H2O
Cu(OAc)2·H2O DMF/Xylene (1:1)
Cu(acac)2
Cu(OTf)2
Cu(acac)2
Cu(acac)2
Cu(acac)2
Cu(acac)2
Cu(acac)2
Cu(acac)2
DMF/Xylene (1:1)
DMF/Xylene (1:1)
DMF
4-CH3C6H4 4-C(CH3)3C6H4
3cg
3ch
3ci
4-CH3C6H4
4-CH3C6H4
4-CH3C6H4
4-CH3C6H4
CH3
2-C2H5C6H4
2-ClC6H4
3-FC6H4
1-naphthyl
C6H5
3-CH3OC6H4
4-FC6H4
4-CF3C6H4
4-CH3C6H4
4-CH3OC6H4
4-C(CH3)3C6H4
2-C2H5C6H4
2-ClC6H4
Xylene
NMP
Toluene
1,4-Dioxene
DMA
3cj
3ck
3da
3db
3dc
3dd
3de
3df
3dg
3dh
3di
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
a The reaction was performed with 1a (0.5 mmol), 2a (1.0 mmol) and
30 t-BuOLi (2.0 equiv) in 1mL of solvent at 120 oC for 12 h. b Isolated yield
The scope on the copper-catalyzed C-H arylation of
thiazolo[3,2-b]-1,2,4-triazoles
1 and aryl iodides 2 was
investigated under the above optimized conditions (Table 2). As
shown in Table 2, it was found that the electron-deficient and
35 electron-rich aryl iodides were reactive and the corresponding
target products were obtained in good to excellent yields (entries
1-11). It was noteworthy that electron-rich aryl iodides gave a
little higher yield than electron-deficient ones (entries 2, 5, 6, 7, 8
CH3
CH3
3-FC6H4
1-naphthyl
3dj
3dk
aThe reaction was performed with 1 (0.5 mmol), 2 (1.0 mmol), t-BuOLi
(2.0 equiv), and Cu(acac)2 (20 mol %) in 1 mL of DMF/Xylene at 120 oC
55 for 12 h. b Isolated yield after column chromatography of the crude.
2
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aliphatic groups (entries 1 vs 34).
Single crystals of 3ba and 3db were obtained successfully, and
ring. Cu(III)-aryl specie C formed at C-5 of the π-excessive
thiazole ring was proposed to be a key intermediate of the
catalytic cycle. Moreover, Cu(III)-aryl specie C formed with
their structures were unambiguously confirmed further by X-ray
crystallography analysis (Figure 1).19 As shown clearly in Figure 45 electron-rich aryl iodides was more stable than electron-deficient
5
1, C-5 arylation rather than C-2 arylation occurred, although C-2
arylation remained dominant from the standpoint of the steric
effect.
one, which was why the former gave higher yields than the latter
one (Table 2). Futhermore, this mechanism can also explain the
aromatic substrates gave better results than the aliphatic one
(Table 2).
Figure 1. Crystal structure of product 3ba (left) and 3db (right)
10
Naturally, we attempted to understand the mechanism for this
arylation reaction. Firstly, 6- methylthiazolo[3,2-b]-1,2,4-triazole
and C6D5I were used as starting materials under the optimized
conditions for mechanistic studies (Scheme 1a). Only compound
50
Scheme 2. Possible Catalytic Cycle for Cu-catalyzed Regioselective
Arylation of Thiazolo[3,2-b]-1,2,4-triazoles
15 5 were obtained in the above reaction, and 4 was not found. It
meant no H-D exchange occurred, and this observation
eliminated the assumption that the reaction proceeded via a
copper-assisted benzyne-type mechanism.20 Secondly; the results
also could eliminate the assumption that the reaction proceeded
20 via Friedel-Crafts alkylations for the reason that no arylated
product was found without bases. Thirdly, t-BuOLi as a base was
not strong enough to remove the H-5 directively according to our
experimental result (Scheme 1b), so the deprotonation-metalation
mechanism16b could also be eliminated in this arylation reaction.
25
Conclusions
In conclusion, we have developed a new copper-catalyzed
55 methodology for the direct, efficient and regioselective C-5
arylation of thiazolo[3,2-b]-1,2,4-triazoles. variety of
substituents on both thiazolo[3,2-b]-1,2,4-triazoles and aryl
iodides were tolerated. In this arylation, the simple Cu(acac)2 was
utilized as the catalyst, and the arylated thiazolo[3,2-b]-1,2,4-
60 triazole derivitives were obtained in high to excellent yields. This
method provides not only a new and useful strategy for the
construction of biologically active heteroaromatic molecules, but
A
also
a new approach for developing Cu-catalyzed C-H
functionalization. Further research will focus on the more
65 detailed machnism, and the application of copper in the synthesis
of other biological heteroaromatic compounds.
(a): C6D5I, Cu(acac)2, t-BuOLi, DMF/xylene
Experimental
General information
1H and 13C NMR spectra were recorded on a Bruker DPX 300
70 MHz spectrometer in CDCl3 or d6-DMSO solution. ESI-MS
spectra were measured on Finnigan Mat TSQ 7000 instruments.
High-resolution electrospray ionization mass spectra (HR-ESI-
MS) were recorded on an Agilent 6540Q-TOF LCMS equipped
with an electrospray ionization (ESI) probe operating in positive-
75 ion mode with direct infusion. Melting points (mp) were
determined with a digital electrothermal apparatus without further
correction. Analytical HPLC was performed on a ShimadzuTM
LC-10A system via a VP-ODS C18 column (250 mm × 4.6 mm,
5 µm particle size) with a CH3CN-H2O mobile phase. TLC
80 analyses were performed on commercial glass plates bearing
0.25-mm layer of Merck Silica gel 60F254. Silica gel (200-300
mesh) was used for column chromatography. Unless otherwise
noted, materials obtained from commercial suppliers were used
without further purification. Solvents were freshly distilled prior
(b): (i) t-BuOLi/DMF/Xylene; (ii) D2O
30
Scheme 1. Mechanistic Studies
Consequently, the possible catalytic cycles was suggested in
Scheme 2. Initially, Cu(acac)2 would be reduced to the active
monovalent specie,21 and then the addition between Cu(I) and
35 heterocycle gave the cationic intermediates A, following the
deprotonation by the base to give the organocopper specie B,22
which possibly underwent the oxidative addition to give the
Cu(III)-aryl specie C. Finally, the desired arylation product was
obtained by a reductive elimination from C releasing the Cu(I)
40 catalyst.16f The thiazolo[3,2-b]-1,2,4-triazole substrate was
composed of π-deficient triazole ring and π-excessive thiazole
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1
to use. Chemical shifts for H NMR are expressed in parts per 55 m/z (%) 345.95 (100) [M+H]+. HRMS (ESI) calcd. for
million (ppm) relative to tetramethylsilane (δ 0.0 ppm). Chemical
shifts for 13C NMR are expressed in ppm relative to CDCl3 (δ
77.16 ppm). Data are reported as follows: chemical shift,
multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, m =
multiplet, bs = broad singlet), coupling constant (Hz), and
integration. All reactions were carried out under nitrogen
atmosphere unless noted.
C17H10F3N3S [MH+]: 346.0620; Found: 346.0624.
6-Phenyl-5-p-tolylthiazolo[3,2-b]-1,2,4-triazole (3ae)
Colorless solid. Yield: 91% (133 mg). Mp: 182-184 oC. H
NMR (300 MHz, CDCl3): δ 8.17 (s, 1H), 7.64-7.61 (m, 2H),
60 7.44-7.42 (m, 3H), 7.25 (d, J = 8.1 Hz, 2H), 7.15 (d, J = 8.1 Hz,
2H), 2.37 (s, 3H). 13C NMR (75 MHz, CDCl3): δ 155.1, 139.3,
129.8, 129.7, 129.6, 129.2, 128.8, 128.2, 127.9, 127.5, 21.3. ESI-
MS m/z (%) 291.95 (100) [M+H]+. HRMS (ESI) calcd. for
C17H13N3S [MH+]: 292.0903; Found: 292.0907.
1
5
Typical Procedure for the Cu-catalyzed Regioselective
10 Arylation of Thiazolo[3,2-b]-1,2,4-triazoles with Aryl Iodides
A suspension of thiazolo[3,2-b]-1,2,4-triazoles (0.50 mmol),
Cu(acac)2 (26.0 mg, 0.10 mmol, 20 mol %), t-BuOLi (80.0 mg,
1.00 mmol, 2.0 equiv), and aryl iodides (1.00 mmol) in
DMF/Xylene (0.5/0.5 mL) was stirred at room temperature for 5
15 min under N2 and heated in oil bath (120 oC) for 12 h. The
reaction mixture was allowed to cool to room temperature and
diluted with ethyl acetate (25 mL). The resulting solution was
washed with brine (3×10 mL), dried over anhydrous Na2SO4 and
concentrated under vacuum to a volume of about 2 mL. The
20 mixture containing the product was subjected to flash
chromatography on silica gel (ethyl acetate / petroleum ether
mixtures) to afford target arylation product.
65 5-(4-Methoxyphenyl)-6-phenylthiazolo[3,2-b]-1,2,4-triazole
(3af)
Colorless solid. Yield: 93% (143 mg). Mp: 113-115 oC. H
1
NMR (300 MHz, CDCl3): δ 8.17 (s, 1H), 7.64-7.61 (m, 2H),
7.44-7.42 (m, 3H), 7.29 (d, J = 8.8 Hz, 2H), 6.88 (d, J = 8.8 Hz,
70 2H), 3.83 (s, 3H). 13C NMR (75 MHz, CDCl3): δ 160.2, 155.0,
130.7, 129.7, 129.6, 128.8, 127.9, 127.6, 127.3, 123.3, 54.9. ESI-
MS m/z (%) 307.95 (100) [M+H]+. HRMS (ESI) calcd. for
C17H13N3OS [MH+]: 308.0852; Found: 308.0856.
5-(4-t-butylphenyl)-6-phenylthiazolo[3,2-b]-1,2,4-triazole (3ag)
1
75
Colorless solid. Yield: 90% (150 mg). Mp: 125-127 oC. H
NMR (300 MHz, CDCl3): δ 8.17 (s, 1H), 7.66-7.62 (m, 2H),
7.46-7.44 (m, 3H), 7.36 (d, J = 8.6 Hz, 2H), 7.29 (d, J = 8.6 Hz,
2H), 1.32 (s, 9H). 13C NMR (75 MHz, CDCl3): δ 155.1, 154.4,
152.4, 129.8, 129.7, 128.8, 128.2, 127.9, 127.8, 127.5, 126.0,
5,6-Diphenylthiazolo[3,2-b]-1,2,4-triazole
(3aa,
Known
Compound)
o
1
25
Colorless solid. Yield: 98% (136 mg). Mp: 191-193 C. H
NMR (300 MHz, CDCl3): δ 8.26 (s, 1H), 7.63-7.60 (m, 2H),
7.44-7.42 (m, 3H), 7.36 (s, 5H). 13C NMR (75 MHz, CDCl3): δ
155.8, 131.2, 129.8, 129.3, 129.1, 128.9, 128.6, 127.9, 127.2.
ESI-MS m/z (%) 278.09 (100) [M+H]+. HRMS (ESI) calcd. for
80 34.8, 31.2. ESI-MS m/z (%) 334.00 (100) [M+H]+. HRMS (ESI)
calcd. for C20H19N3S [MH+]: 334.1372; Found: 334.1377.
5-(2-Ethylphenyl)-6-phenylthiazolo[3,2-b]-1,2,4-triazole (3ah)
30 C16H11N3S [MH+]: 278.0746; Found: 278.0749.
Colorless solid. Yield: 96% (147 mg). Mp: 108-110 oC. H
1
5-(3-Methoxyphenyl)-6-phenylthiazolo[3,2-b]-1,2,4-triazole
(3ab)
NMR (300 MHz, CDCl3): δ 8.23 (s, 1H), 7.60-7.56 (m, 2H),
85 7.43-7.24 (m, 7H), 2.49 (q, J = 7.5 Hz, 2H), 1.01 (t, J = 7.5 Hz,
3H). 13C NMR (75 MHz, CDCl3): δ 155.1, 143.9, 139.4, 132.0,
129.4, 129.2, 128.7, 128.6, 128.4, 127.9, 127.5, 126.3, 125.9,
26.0, 14.8. ESI-MS m/z (%) 306.00 (100) [M+H]+. HRMS (ESI)
calcd. for C18H15N3S [MH+]: 306.1059; Found: 306.1062.
Colorless oil. Yield: 94% (144 mg). 1H NMR (300 MHz,
CDCl3): δ 8.17 (s, 1H), 7.65-7.62 (m, 2H), 7.45-7.43 (m, 3H),
35 7.26 (d, J = 15.8 Hz, 1H), 6.96-6.87 (m, 3H), 3.69 (s, 3H). 13
C
NMR (75 MHz, CDCl3): δ 159.8, 155.2, 132.3 130.1, 129.8,
128.8, 128.3, 127.8, 127.1, 126.6, 121.5, 114.9, 55.2. ESI-MS
m/z (%) 308.05 (100) [M+H]+. HRMS (ESI) calcd. for
C17H13N3OS [MH+]: 308.0852; Found: 308.0856.
90 5-(2-Chlorophenyl)-6-phenylthiazolo[3,2-b]-1,2,4-triazole (3ai)
Colorless solid. Yield: 88% (137 mg). Mp: 147-149 oC. H
1
NMR (300 MHz, CDCl3): δ 8.22 (s, 1H), 7.60-7.56 (m, 2H),
7.50-7.27 (m, 7H). 13C NMR (75 MHz, CDCl3): δ 155.3, 135.1,
133.3, 131.1, 130.4, 129.7, 128.8, 128.7, 127.6, 127.3, 123.4.
95 ESI-MS m/z (%) 311.95 (100) [M+H]+. HRMS (ESI) calcd. for
C16H10ClN3S [MH+]: 312.0357; Found: 312.0359.
40 5-(4-Fluorophenyl)-6-phenylthiazolo[3,2-b]-1,2,4-triazole (3ac)
1
Colorless solid. Yield: 89% (131 mg). Mp: 186-188 oC. H
NMR (300 MHz, CDCl3): δ 8.25 (s, 1H), 7.61-7.58 (m, 2H),
7.45-7.43 (m, 3H), 7.37-7.32 (m, 2H), 7.06 (t, J = 8.5 Hz, 2H).
13C NMR (75 MHz, CDCl3): δ 163.0 (JCF = 250.6 Hz), 155.9,
45 131.3 (JCF = 8.2 Hz), 129.9, 129.7, 128.9, 128.7, 127.7, 127.3,
127.2, 125.9, 116.3 (JCF = 22.0 Hz). ESI-MS m/z (%) 296.05
(100) [M+H]+. HRMS (ESI) calcd. For C16H10FN3S [MH+]:
296.0652; Found: 296.0655.
5-(3-Fluorophenyl)-6-phenylthiazolo[3,2-b]-1,2,4-triazole (3aj)
1
Colorless solid. Yield: 82% (121 mg). Mp: 151-153 oC. H
NMR (300 MHz, CDCl3): δ 8.19 (s, 1H), 7.63-7.60 (m, 2H),
100 7.47-7.45 (m, 3H), 7.34 (dd, J = 14.5, 7.1 Hz, 1H), 7.17-7.05 (m,
3H). 13C NMR (75 MHz, CDCl3): δ 162.8 (JCF = 248.2 Hz), 155.4,
154.5, 133.3, 133.2, 130.8 (JCF = 8.5 Hz), 130.1, 129.7, 129.0,
127.3, 125.6, 125.1 (JCF = 2.6 Hz), 116.2 (JCF = 22.1 Hz). ESI-
MS m/z (%) 295.95 (100) [M+H]+. HRMS (ESI) calcd. for
105 C16H10FN3S [MH+]: 296.0652; Found: 296.0658.
5-(4-(Trifluoromethyl)phenyl)-6-phenylthiazolo[3,2-b]-1,2,4-
50 triazole (3ad)
1
Colorless solid. Yield: 85% (147 mg). Mp: 141-143 oC. H
NMR (300 MHz, CDCl3): δ 8.21 (s, 1H), 7.63-7.59 (m, 4H),
7.50-7.46 (m, 5H). 13C NMR (75 MHz, CDCl3): δ 155.6, 134.9,
130.2, 129.8, 129.6, 129.1, 127.2, 126.1, 126.0, 125.4. ESI-MS
5-(Naphthalen-1-yl)-6-phenylthiazolo[3,2-b]-1,2,4-triazole
(3ak)
4
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Yellow solid. Yield: 97% (159 mg). Mp: 142-144 oC. 1H NMR
NMR (300 MHz, CDCl3): δ 8.16 (s, 1H), 7.54 (q, J = 8.6 Hz, 4H),
(300 MHz, CDCl3): δ 8.27 (s, 1H), 7.96-7.89 (m, 3H), 7.60-7.43 55 7.29 (d, J = 8.9 Hz, 2H), 6.90 (d, J = 8.9 Hz, 2H), 3.84 (s, 3H).
(m, 6H), 7.30-7.21 (m, 3H). 13C NMR (75 MHz, CDCl3): δ 155.5,
155.0, 133.7, 132.0, 130.5, 130.3, 129.4, 128.7, 128.5, 127.3,
126.6, 125.4, 125.1. ESI-MS m/z (%) 328.00 (100) [M+H]+.
HRMS (ESI) calcd. for C20H13N3S [MH+]: 328.0903; Found:
328.0906.
13C NMR (75 MHz, CDCl3): δ 160.4, 155.0, 154.4, 138.0, 132.1,
131.1, 130.7, 127.9, 126.8, 126.4, 123.9, 122.9, 114.7, 55.4. ESI-
MS m/z (%) 385.95 (100) [M+H]+. HRMS (ESI) calcd. for
C17H12BrN3OS [MH+]: 385.9957; Found: 385.9958.
5
60 5-(4-t-butylphenyl)-6-(4-bromophenyl)thiazolo[3,2-b]-1,2,4-
triazole (3bg)
6-(4-Bromophenyl)-5-phenylthiazolo[3,2-b]-1,2,4-triazole (3ba)
1
Colorless solid. Yield: 94% (194 mg). Mp: 168-170 oC. H
1
Colorless solid. Yield: 95% (169 mg). Mp: 175-177 oC. H
NMR (300 MHz, CDCl3): δ 8.17 (s, 1H), 7.55 (q, J = 8.7 Hz, 4H),
7.39 (d, J = 9.1 Hz, 2H), 7.28 (d, J = 9.1 Hz, 2H), 1.34 (s, 9H).
65 13C NMR (75 MHz, CDCl3): δ 155.2, 154.2, 152.8, 138.1, 132.1,
131.2, 128.9, 127.8, 126.8, 126.7, 126.2, 124.0, 34.8, 31.2. ESI-
MS m/z (%) 412.95 (100) [M+H]+. HRMS (ESI) calcd. for
C20H18BrN3S [MH+]: 412.0478; Found: 412.0480.
10 NMR (300 MHz, CDCl3): δ 8.17 (s, 1H), 7.54 (q, J = 8.6 Hz, 4H),
7.38 (m, 5H). 13C NMR (75 MHz, CDCl3): δ 155.2, 154.7, 138.1,
132.1, 131.2, 130.8, 129.4, 129.3, 129.2, 127.9, 127.2, 127.1,
126.6, 124.1. ESI-MS m/z (%) 355.90 (100) [M+H]+. HRMS
(ESI) calcd. for C16H10BrN3S [MH+]: 355.9852; Found: 355.9852.
15 6-(4-Bromophenyl)-5-(3-methoxyphenyl)thiazolo[3,2-b]-1,2,4-
triazole (3bb)
6-(4-Bromophenyl)-5-(2-ethylphenyl)thiazolo[3,2-b]-1,2,4-
70 triazole (3bh)
Colorless solid. Yield: 92% (178 mg). Mp: 133-135 oC. H
1
Colorless solid. Yield: 93% (179 mg). Mp: 132-134 oC. H
1
NMR (300 MHz, CDCl3): δ 8.18 (s, 1H), 7.55 (q, J = 8.9 Hz, 4H),
7.31 (d, J = 8.1 Hz, 1H), 6.95-6.88 (m, 3H), 3.75 (s, 3H). 13C
20 NMR (75 MHz, CDCl3): δ 159.9, 155.3, 154.6, 138.1, 132.0,
131.2, 130.4, 127.7, 127.0, 126.6, 124.2, 121.7, 114.9, 55.3. ESI-
MS m/z (%) 385.90 (100) [M+H]+. HRMS (ESI) calcd. for
C17H12BrN3OS [MH+]: 385.9957; Found: 385.9958.
NMR (300 MHz, CDCl3): δ 8.21 (s, 1H), 7.51-7.45 (m, 4H),
7.43-7.25 (m, 4H), 2.49 (q, J = 7.6 Hz, 2H), 1.04 (t, J = 7.6 Hz,
3H). 13C NMR (75 MHz, CDCl3): δ 155.3, 155.1, 143.9, 137.8,
75 131.8, 130.0, 129.1, 127.9, 126.8, 126.5, 123.7, 26.1, 14.8. ESI-
MS m/z (%) 383.95 (100) [M+H]+. HRMS (ESI) calcd. for
C18H14BrN3S [MH+]: 384.0165; Found: 384.0166.
6-(4-Bromophenyl)-5-(4-fluorophenyl)thiazolo[3,2-b]-1,2,4-
25 triazole (3bc)
6-(4-Bromophenyl)-5-(2-chlorophenyl)thiazolo[3,2-b]-1,2,4-
triazole (3bi)
Colorless solid. Yield: 86% (161 mg). Mp: 148-150 oC. H
1
1
80
Colorless solid. Yield: 85% (166 mg). Mp: 157-159 oC. H
NMR (300 MHz, CDCl3): δ 8.21 (s, 1H), 7.50 (q, J = 8.6 Hz, 4H),
7.45-7.31 (m, 4H). 13C NMR (75 MHz, CDCl3): δ 155.6, 155.4,
137.9, 135.0, 133.1, 131.4, 130.2, 129.5, 129.2, 127.5, 126.5,
124.1, 123.9. ESI-MS m/z (%) 389.85 (100) [M+H]+. HRMS
NMR (300 MHz, CDCl3): δ 8.17 (s, 1H), 7.53 (q, J = 8.5 Hz, 4H),
7.37-7.33 (m, 2H), 7.09 (t, J = 8.4 Hz, 2H). 13C NMR (75 MHz,
CDCl3): δ 163.2 (JCF = 251.1 Hz), 155.3, 154.5, 138.2, 132.2,
30 131.3 (JCF = 8.4 Hz), 131.1, 130.1, 127.3, 126.9, 126.6, 126.4,
124.3, 116.6 (JCF = 22.0 Hz), 112.2. ESI-MS m/z (%) 373.90
(100) [M+H]+. HRMS (ESI) calcd. for C16H9BrFN3S [MH+]:
373.9757; Found: 373.9759.
85 (ESI) calcd. for C16H9BrClN3S [MH+]: 389.9462; Found:
389.9463.
6-(4-Bromophenyl)-5-(3-fluorophenyl)thiazolo[3,2-b]-1,2,4-
triazole (3bj)
6-(4-Bromophenyl)-5-(4-(trifluoromethyl)phenyl)thiazolo[3,2-
35 b]-1,2,4-triazole (3bd)
1
Colorless solid. Yield: 80% (150 mg). Mp: 153-155 oC. H
1
Colorless solid. Yield: 79% (168 mg). Mp: 196-197 oC. H
90 NMR (300 MHz, CDCl3): δ 8.18 (s, 1H), 7.55 (q, J = 8.6 Hz, 4H),
7.37 (q, J = 7.2 Hz, 1H), 7.16-7.06 (m, 3H). 13C NMR (75 MHz,
CDCl3): δ 162.4 (JCF = 248.8 Hz), 155.5, 154.6, 138.2, 132.8,
132.3, 131.2, 131.0 (JCF = 8.6 Hz), 127.7, 126.2, 125.1, 124.5,
116.4 (JCF = 22.0 Hz). ESI-MS m/z (%) 373.90 (100) [M+H]+.
95 HRMS (ESI) calcd. for C16H9BrFN3S [MH+]: 373.9757; Found:
373.9758.
NMR (300 MHz, CDCl3): δ 8.22 (s, 1H), 7.63 (q, J = 8.5 Hz, 4H),
7.49 (d, J = 8.5 Hz, 4H), 13C NMR (75 MHz, CDCl3): δ 155.7,
138.4, 134.6, 132.4, 131.2, 129.6, 128.3,126.3, 126.2, 126.1,
40 125.8, 125.4, 124.7, 121.8. ESI-MS m/z (%) 423.90 (100)
[M+H]+. HRMS (ESI) calcd. for C17H9BrF3N3S [MH+]: 423.9725;
Found: 423.9723.
6-(4-Bromophenyl)-5-p-tolylthiazolo[3,2-b]-1,2,4-triazole (3be)
6-(4-Bromophenyl)-5-(naphthalen-1-yl)thiazolo[3,2-b]-1,2,4-
triazole (3bk)
1
Colorless solid. Yield: 90% (167 mg). Mp: 146-148 oC. H
45 NMR (300 MHz, CDCl3): δ 8.17 (s, 1H), 7.54 (q, J = 8.7 Hz, 4H),
7.25 (d, J = 8.2 Hz, 2H), 7.18 (d, J = 8.2 Hz, 2H), 2.39 (s, 3H).
13C NMR (75 MHz, CDCl3): δ 155.1, 154.5, 139.6, 138.0, 132.1,
131.2, 129.9, 129.2, 128.1, 127.9, 126.8, 123.9, 21.3. ESI-MS
m/z (%) 369.95 (100) [M+H]+. HRMS (ESI) calcd. for
50 C17H12BrN3S [MH+]: 370.0008; Found: 370.0010.
1
Colorless solid. Yield: 95% (193 mg). Mp: 204-206 oC. H
100 NMR (300 MHz, CDCl3): δ 8.27 (s, 1H), 8.00-7.85 (m, 3H),
7.58-7.44 (m, 6H), 7.37-7.30 (m, 2H). 13C NMR (75 MHz,
CDCl3): δ 155.6, 155.3, 137.7, 133.8, 131.9, 131.8, 130.7, 130.2,
130.0, 128.9, 128.7, 127.7, 127.5, 126.7, 126.6, 125.4, 124.9,
123.8. ESI-MS m/z (%) 405.95 (100) [M+H]+. HRMS (ESI)
105 calcd. for C20H12BrN3S [MH+]: 406.0008; Found: 406.0008.
6-(4-Bromophenyl)-5-(4-methoxyphenyl)thiazolo[3,2-b]-1,2,4-
triazole (3bf)
5-Phenyl-6-p-tolylthiazolo[3,2-b]-1,2,4-triazole (3ca)
1
Colorless solid. Yield: 91% (176 mg). Mp: 144-146 oC. H
Colorless solid. Yield: 98% (143 mg). Mp: 187-189 oC. H
1
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Page 6 of 8
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NMR (300 MHz, CDCl3): δ 8.17 (s, 1H), 7.51 (d, J = 8.1 Hz, 2H),
7.36 (d, J = 8.5 Hz, 2H), 7.30 (d, J = 8.5 Hz, 2H), 7.25 (d, J = 8.0
7.36 (m, 5H), 7.25 (m, 2H), 2.40 (s, 3H). 13C NMR (75 MHz, 55 Hz, 2H), 2.41 (s, 3H), 1.32 (s, 9H). 13C NMR (75 MHz, CDCl3): δ
CDCl3): δ 155.2, 139.9, 131.4, 129.6, 129.3, 129.1, 128.4, 126.6,
124.8, 21.5. ESI-MS m/z (%) 292.00 (100) [M+H]+. HRMS (ESI)
calcd. for C17H13N3S [MH+]: 292.0903; Found: 292.0907.
155.1, 154.4, 152.3, 139.8, 129.6, 128.8, 128.3, 127.9, 126.9,
126.0, 125.0, 34.8, 31.2, 21.5. ESI-MS m/z (%) 348.05 (100)
[M+H]+. HRMS (ESI) calcd. for C21H21N3S [MH+]: 348.1529;
Found: 348.1532.
5
5-(3-Methoxyphenyl)-6-p-tolylthiazolo[3,2-b]-1,2,4-triazole
(3cb)
60 5-(2-Ethylphenyl)-6-p-tolylthiazolo[3,2-b]-1,2,4-triazole (3ch)
1
Colorless solid. Yield: 96% (154 mg). Mp: 117-119 oC. H
1
Colorless solid. Yield: 95% (152 mg). Mp: 105-107 oC. H
NMR (300 MHz, CDCl3): δ 8.16 (s, 1H), 7.52 (d, J = 8.1 Hz, 2H),
NMR (300 MHz, CDCl3): δ 8.21 (s, 1H), 7.47 (d, J = 8.2 Hz, 2H),
7.40 (m, 2H), 7.27 (m, 2H), 7.14 (d, J = 8.2 Hz, 2H), 2.49 (q, J =
7.6 Hz, 2H), 2.33 (s, 3H), 1.02 (t, J = 7.6 Hz, 3H). 13C NMR (75
65 MHz, CDCl3): δ 155.1, 144.0, 139.5, 132.1, 130.0, 129.6, 129.3,
129.1, 128.5, 126.3, 125.1, 125.0, 26.1, 21.4, 14.8. ESI-MS m/z
(%) 320.05 (100) [M+H]+. HRMS (ESI) calcd. for C19H17N3S
[MH+]: 320.1216; Found: 320.1220.
10 7.29-7.23 (m, 3H), 6.97-6.89 (m, 3H), 3.71 (s, 3H), 2.40 (s, 3H).
13C NMR (75 MHz, CDCl3): δ 159.8, 155.1, 154.4, 139.9, 132.5,
130.9, 130.1, 129.6, 129.5, 128.8, 128.5, 126.5, 124.8, 121.6,
114.7, 55.2, 21.5. ESI-MS m/z (%) 322.00 (100) [M+H]+. HRMS
(ESI) calcd. for C18H15N3OS [MH+]: 322.1009; Found: 322.1013.
15 5-(4-Fluorophenyl)-6-p-tolylthiazolo[3,2-b]-1,2,4-triazole (3cc)
5-(2-Chlorophenyl)-6-p-tolylthiazolo[3,2-b]-1,2,4-triazole (3ci)
Yellow solid. Yield: 91% (141 mg). Mp: 187-189 oC. 1H NMR
(300 MHz, CDCl3): δ 8.17 (s, 1H), 7.48 (d, J = 8.0 Hz, 2H), 7.38-
7.33 (m, 2H), 7.26-7.23 (m, 2H), 7.06 (t, J = 8.5 Hz, 2H), 2.40 (s,
3H). 13C NMR (75 MHz, CDCl3): δ 163.0 (JCF = 250.4 Hz), 155.2,
20 154.4, 140.1, 131.2 (JCF = 8.3 Hz), 130.1, 129.7, 129.5, 128.8,
128.5, 127.4, 125.4, 124.5, 116.3 (JCF = 21.9 Hz), 114.1, 21.5.
ESI-MS m/z (%) 310.00 (100) [M+H]+. HRMS (ESI) calcd. for
C17H12FN3S [MH+]: 310.0809; Found: 310.0813.
1
70
Colorless solid. Yield: 88% (143 mg). Mp: 125-127 oC. H
NMR (300 MHz, CDCl3): δ 8.21 (s, 1H), 7.50-7.36 (m, 5H), 7.31
(dd, J = 7.4, 1.3 Hz, 1H), 7.17 (d, J = 8.0 Hz, 2H), 2.35 (s, 3H).
13C NMR (75 MHz, CDCl3): δ 155.6, 155.3, 139.8, 135.1, 133.3,
131.0, 130.5, 130.3, 130.0, 129.4, 128.7, 127.3, 124.7, 124.0,
75 122.6, 114.1, 21.4. ESI-MS m/z (%) 326.00 (100) [M+H]+.
HRMS (ESI) calcd. for C17H12ClN3S [MH+]: 326.0513; Found:
326.0517.
5-(4-(Trifluoromethyl)phenyl)-6-p-tolylthiazolo[3,2-b]-1,2,4-
25 triazole (3cd)
5-(3-Fluorophenyl)-6-p-tolylthiazolo[3,2-b]-1,2,4-triazole (3cj)
Colorless solid. Yield: 88% (158 mg). Mp: 138-140 oC. H
1
1
Colorless solid. Yield: 83% (128 mg). Mp: 148-150 oC. H
NMR (300 MHz, CDCl3): δ 8.18 (s, 1H), 7.61 (d, J = 8.1 Hz, 2H),
7.49 (d, J = 8.3 Hz, 4H), 7.27 (d, J = 8.1 Hz, 2H), 2.42 (s, 3H).
13C NMR (75 MHz, CDCl3): δ 155.5, 154.6, 140.5, 135.1, 131.0,
30 130.6, 129.8, 129.6, 129.5, 126.1, 126.0, 125.5, 124.7, 124.2,
121.9, 114.0, 21.5. ESI-MS m/z (%) 360.00 (100) [M+H]+.
HRMS (ESI) calcd. for C18H12F3N3S [MH+]: 360.0777; Found:
360.0781.
80 NMR (300 MHz, CDCl3): δ 8.17 (s, 1H), 7.49 (d, J = 8.6 Hz, 2H),
7.37-7.25 (m, 3H), 7.16 (d, J = 6.9 Hz, 1H), 7.07 (d, J = 8.6 Hz,
2H), 2.41 (s, 3H). 13C NMR (75 MHz, CDCl3): δ 162.8 (JCF
=
248.1 Hz), 155.4, 154.6, 140.4, 133.5, 133.4, 130.8 (JCF = 8.2 Hz),
129.8, 129.6, 129.1, 125.0, 124.4, 116.2 (JCF = 21.9 Hz), 21.5.
85 ESI-MS m/z (%) 310.00 (100) [M+H]+. HRMS (ESI) calcd. for
C17H12FN3S [MH+]: 310.0809; Found: 310.0813.
5,6-Di-p-tolylthiazolo[3,2-b]-1,2,4-triazole (3ce)
5-(Naphthalen-1-yl)-6-p-tolylthiazolo[3,2-b]-1,2,4-triazole (3ck)
Yellow solid. Yield: 92% (140 mg). Mp: 203-205 oC. 1H NMR
(300 MHz, CDCl3): δ 8.16 (s, 1H), 7.51 (d, J = 8.1 Hz, 2H), 7.25
(dd, J = 10.7, 5.0 Hz, 4H), 7.15 (d, J = 8.1 Hz, 2H), 2.38 (d, J =
7.9 Hz, 6H). 13C NMR (75 MHz, CDCl3): δ 155.1, 139.8, 139.1,
129.8, 129.6, 129.1, 128.4, 128.0, 126.8, 124.9, 114.1, 21.5, 21.3.
1
Colorless solid. Yield: 96% (164 mg). Mp: 142-144 oC. H
35
NMR (300 MHz, CDCl3): δ 8.25 (s, 1H), 7.96-7.90 (m, 3H),
90 7.59-7.44 (m, 6H), 7.03 (d, J = 7.9 Hz, 2H), 2.26 (s, 3H). 13
C
NMR (75 MHz, CDCl3): δ 155.6, 155.2, 139.5, 133.7, 132.2,
130.3, 129.2, 128.6, 128.3, 127.2, 126.5,, 125.4, 125.2, 124.8,
124.5, 124.0, 119.1, 114.1, 21.3. ESI-MS m/z (%) 342.05 (100)
[M+H]+. HRMS (ESI) calcd. for C21H15N3S [MH+]: 342.1059;
95 Found: 342.1065.
40 ESI-MS m/z (%) 306.00 (100) [M+H]+. HRMS (ESI) calcd. for
C18H15N3S [MH+]: 306.1059; Found: 306.1062.
5-(4-Methoxyphenyl)-6-p-tolylthiazolo[3,2-b]-1,2,4-triazole
(3cf)
6-Methyl-5-phenylthiazolo[3,2-b]-1,2,4-triazole (3da)
Colorless solid. Yield: 93% (158 mg). Mp: 168-169 oC. H
1
Colorless oil. Yield: 90% (97 mg). 1H NMR (300 MHz,
CDCl3): δ 8.17 (s, 1H), 7.50-7.42 (m, 5H), 2.64 (s, 3H). 13C NMR
(75 MHz, CDCl3): δ 155.2, 154.5, 131.1, 130.9, 129.1, 129.0,
100 128.9, 125.6, 125.1, 114.1, 11.7. ESI-MS m/z (%) 216.00 (100)
[M+H]+. HRMS (ESI) calcd. for C11H9N3S [MH+]: 216.0590;
Found: 216.0591.
45 NMR (300 MHz, CDCl3): δ 8.15 (s, 1H), 7.51 (d, J = 8.5 Hz, 2H),
7.30 (d, J = 8.1 Hz, 2H), 7.23 (d, J = 8.1 Hz, 2H), 6.88 (d, J = 8.5
Hz, 2H), 3.83 (s, 3H), 2.39 (s, 3H). 13C NMR (75 MHz, CDCl3): δ
160.1, 155.0, 139.7, 130.6, 129.5, 126.6, 124.9, 123.5, 114.5,
55.0, 21.5. ESI-MS m/z (%) 322.00 (100) [M+H]+. HRMS (ESI)
50 calcd. for C18H15N3OS [MH+]: 322.1009; Found: 322.1012.
5-(3-Methoxyphenyl)-6-methylthiazolo[3,2-b]-1,2,4-triazole
(3db)
5-(4-t-butylphenyl)-6-p-tolylthiazolo[3,2-b]-1,2,4-triazole (3cg)
Colorless solid. Yield: 92% (160 mg). Mp: 119-121 oC. H
1
1
105
Colorless solid. Yield: 98% (120 mg). Mp: 105-106 oC. H
NMR (300 MHz, CDCl3): δ 8.15 (s, 1H), 7.52 (d, J = 8.0 Hz, 2H),
NMR (300 MHz, CDCl3): δ 8.18 (s, 1H), 7.41 (t, J = 7.9 Hz, 1H),
6
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7.07 (d, J = 7.5 Hz, 1H), 6.99 (d, J = 9.6 Hz, 2H), 3.87 (s, 3H),
(%) 244.00 (100) [M+H]+. HRMS (ESI) calcd. for C13H13N3S
2.66 (s, 3H). 13C NMR (75 MHz, CDCl3): δ 160.0, 155.3, 132.3, 55 [MH+]: 244.0903; Found: 244.0907.
130.3, 125.4, 125.3, 121.4, 114.9, 114.3, 114.1, 55.4, 11.8. ESI-
5-(2-Chlorophenyl)-6-methylthiazolo[3,2-b]-1,2,4-triazole (3di)
MS m/z (%) 246.00 (100) [M+H]+. HRMS (ESI) calcd. for
C12H11N3OS [MH+]: 246.0696; Found: 246.0698.
Colorless oil. Yield: 87% (109 mg). 1H NMR (300 MHz,
CDCl3):δ 8.18 (s, 1H), 7.55 (d, J = 8.3 Hz, 1H), 7.47-7.35 (m,
3H), 2.44 (s, 3H). 13C NMR (75 MHz, CDCl3): δ 155.3, 135.1,
5
5-(4-Fluorophenyl)-6-methylthiazolo[3,2-b]-1,2,4-triazole (3dc)
o
Colorless solid. Yield: 83% (97 mg). Mp: 94-96 C. 1H NMR 60 133.0, 131.1, 130.3, 129.2, 127.5, 127.2, 121.7, 114.1, 11.6. ESI-
(300 MHz, CDCl3): δ 8.17 (s, 1H), 7.49-7.45 (m, 2H), 7.20 (t, J =
8.5 Hz, 2H), 2.61 (s, 3H). 13C NMR (75 MHz, CDCl3): δ 163.0
MS m/z (%) 249.95 (100) [M+H]+. HRMS (ESI) calcd. for
C11H8ClN3S [MH+]: 250.0200; Found: 250.0202.
10 (JCF = 250.2 Hz), 155.2, 154.3, 131.0 (JCF = 8.4 Hz), 127.1, 125.3,
124.4, 116.3 (JCF = 21.9 Hz), 11.5. ESI-MS m/z (%) 234.00 (100)
[M+H]+. HRMS (ESI) calcd. for C11H8FN3S [MH+]: 234.0496;
Found: 234.0495.
5-(3-Fluorophenyl)-6-methylthiazolo[3,2-b]-1,2,4-triazole (3dj)
1
Colorless solid. Yield: 81% (94 mg). Mp: 114-116 oC. H
65 NMR (300 MHz, CDCl3): δ 8.18 (s, 1H), 7.51-7.44 (m, 1H),
7.29-7.12 (m, 3H), 2.66 (s, 3H). 13C NMR (75 MHz, CDCl3): δ
162.9 (JCF = 248.4 Hz), 155.4, 154.4, 130.9 (JCF = 8.6 Hz), 125.8,
124.8, 116.2, 116.0 (JCF = 22.0 Hz), 114.1, 11.7. ESI-MS m/z (%)
234.00 (100) [M+H]+. HRMS (ESI) calcd. for C11H8FN3S [MH+]:
70 234.0496; Found: 234.0499.
5-(4-(Trifluoromethyl)phenyl)-6-methylthiazolo[3,2-b]-1,2,4-
15 triazole (3dd)
1
Colorless solid. Yield: 76% (108 mg). Mp: 120-122 oC. H
NMR (300 MHz, CDCl3): δ 8.20 (s, 1H), 7.77 (d, J = 8.2 Hz, 2H),
7.62 (d, J = 8.2 Hz, 2H), 2.68 (s, 3H). 13C NMR (75 MHz,
CDCl3): δ 155.7, 134.8, 131.2, 130.7, 129.3, 126.3, 126.2, 126.1,
20 123.9, 122.0, 114.1, 11.8. ESI-MS m/z (%) 284.00 (100) [M+H]+.
HRMS (ESI) calcd. for C12H8F3N3S [MH+]: 284.0464; Found:
284.0468.
6-Methyl-5-(naphthalen-1-yl)thiazolo[3,2-b]-1,2,4-triazole
(3dk)
Yellow oil. Yield: 93% (123 mg). 1H NMR (300 MHz, CDCl3):
δ 8.23 (s, 1H), 8.02-7.95 (m, 2H), 7.86 (d, J = 9.2 Hz, 1H), 7.62-
75 7.55 (m, 4H), 2.40 (s, 3H). 13C NMR (75 MHz, CDCl3): δ 155.4,
155.2, 133.7, 132.2, 130.3, 130.0, 128.7, 127.5, 127.3, 127.1,
126.6, 125.2, 125.0, 122.8, 114.1, 11.6. ESI-MS m/z (%) 266.05
(100) [M+H]+. HRMS (ESI) calcd. for C15H11N3S [MH+]:
266.0746; Found: 266.0748.
6-Methyl-5-p-tolylthiazolo[3,2-b]-1,2,4-triazole (3de)
1
Colorless solid. Yield: 93% (107 mg). Mp: 103-105 oC. H
25 NMR (300 MHz, CDCl3): δ 8.17 (s, 1H), 7.38 (d, J = 8.1 Hz, 2H),
7.30 (d, J = 8.1 Hz, 2H), 2.63 (s, 3H), 2.43 (s, 3H). 13C NMR (75
MHz, CDCl3): δ 155.2, 139.1, 129.8, 128.9, 128.0, 125.7, 124.4,
123.5, 114.1, 21.3, 11.7. ESI-MS m/z (%) 230.00 (100) [M+H]+.
ESI-MS m/z (%) 284.00 (100) [M+H]+. HRMS (ESI) calcd. for
30 C12H11N3S [MH+]: 230.0746; Found: 230.0748.
80 6-Methyl-5-D5-phenylthiazolo[3,2-b]-1,2,4-triazole (5)
o
Colorless solid. Yield: 88% (97 mg). Mp: 82-83 C. 1H NMR
(300 MHz, CDCl3): δ 8.17 (s, 1H), 2.64 (s, 3H). 13C NMR (75
MHz, CDCl3): δ 155.2, 130.9, 128.9, 128.8, 128.4, 128.3, 128.1,
125.4, 125.0, 114.1, 11.7. ESI-MS m/z (%) 221.05 (100) [M+H]+.
85 HRMS (ESI) calcd. for C11H4D5N3S [MH+]: 221.0904; Found:
221.0906.
5-(4-Methoxyphenyl)-6-methylthiazolo[3,2-b]-1,2,4-triazole
(3df)
1
Colorless solid. Yield: 92% (113 mg). Mp: 102-104 oC. H
NMR (300 MHz, CDCl3): δ 8.16 (s, 1H), 7.41 (d, J = 8.7 Hz, 2H),
35 7.01 (d, J = 8.7 Hz, 2H), 3.88 (s, 3H), 2.61 (s, 3H). 13C NMR (75
MHz, CDCl3): δ 160.1, 155.1, 139.3, 130.4, 125.5, 124.4, 123.5,
123.3, 114.6, 55.4, 11.6. ESI-MS m/z (%) 246.00 (100) [M+H]+.
HRMS (ESI) calcd. for C12H11N3OS [MH+]: 246.0696; Found:
246.0699.
Acknowledgment
We gratefully acknowledge the financial support of National
Natural Science Foundation of China (No. 21102073, 21072093),
90 National Basic Research Program of China (2011CB808600), and
the Natural Science Foundation of Jiangsu (BK2011055,
BK2011551).
40 5-(4-t-butylphenyl)-6-methylthiazolo[3,2-b]-1,2,4-triazole (3dg)
1
Colorless solid. Yield: 99% (134 mg). Mp: 109-111 oC. H
Notes and references
NMR (300 MHz, CDCl3): δ 8.17 (s, 1H), 7.51 (d, J = 8.4 Hz, 2H),
7.42 (d, J = 8.4 Hz, 2H), 2.65 (s, 3H), 1.37 (s, 9H). 13C NMR (75
MHz, CDCl3): δ 155.2, 152.2, 128.7, 128.2, 126.1, 125.7, 124.8,
45 114.1, 34.8, 31.2, 11.7. ESI-MS m/z (%) 272.00 (74) [M+H]+.
HRMS (ESI) calcd. for C15H17N3S [MH+]: 272.1216; Found:
272.1218.
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