Copper-Catalyzed Benzylic C—H Functionalization, Oxidation and Cyclization of Methylarenes: Direct Access to 2-Arylbenzothiazoles

Article abstract of DOI:10.1002/cjoc.201900340

The direct C—H functionalization of methylarenes is of great significance. Herein, a copper-catalyzed oxidative C—N/C—S bond formation through benzylic C(sp³)—H functionalization, oxidation and cyclization of methylarenes is reported. Various 2-arylbenzothiazoles have been synthesized in moderate to excellent yields with readily available o-iodoaniline, potassium sulfide, and methylarenes as raw materials.

Full text of DOI:10.1002/cjoc.201900340

copper, sulfur heterocycles, oxidation, cyclization
中
国 化 学
Copper-Catalyzed Benzylic C—H Functionalization, Oxidation and
Cyclization of Methylarenes: Direct Access to 2-Arylbenzothiazoles†
Wentao Yu, Wanqing Wu, and Huanfeng Jiang*
Key Lab of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology,
Guangzhou, Guangdong 510640, China
Cite this paper: Chin. J. Chem. 2019, 37, 1158—1166. DOI: 10.1002/cjoc.201900340
Summary of main observation and conclusion The direct C—H functionalization of methylarenes is of great significance. Herein, a copper-catalyzed
oxidative C—N/C—S bond formation through benzylic C(sp3)—H functionalization, oxidation and cyclization of methylarenes is reported. Various
2-arylbenzothiazoles have been synthesized in moderate to excellent yields with readily available o-iodoaniline, potassium sulfide, and methylarenes as
raw materials.
potassium iodide-catalyzed three-component synthesis of
Background and Originality Content
quinazolines via benzaldehyde intermediate. Hiyama[20] and
Matsuzaka[21] reported a direct dehydrative condensation of ben-
As an inexpensive, fundamental and important feedstock for
the petrochemical industry, methylarenes have long been regard-
zylic C—H bonds. A practical Brønsted acid promoted-benzylic
ed as one of the most widely used raw materials for a great varie-
C—H functionalization of 2-alkylazaarenes and nucleophilic addi-
ty of organic transformations. Therefore, the selective benzylic
tion to nitroso compounds was also developed by Yang.[22] Punni-
C(sp3)—H functionalization is particularly important, which pro-
yamurthy developed a copper(II)-catalyzed tandem cross-coupling
vides a strategic means to utilize this resource. Recent research in
of methylarenes with anilines followed by TMSN3 via triple C—N
benzylic C(sp3)—H functionalization has mostly focused on mono
bond formation.[23] To date, constructing C—N/C—S bonds
C(sp3)—H functionalization for the construction of C—C,[1] C—N,[2]
through C(sp3)—H functionalization of methylarenes, to the best
C—O,[3] C—halo,[4] C—B,[5] and C—Si[6] single bonds, which has
of our knowledge, has not been reported. In addition, the selec-
become a powerful method in synthetic chemistry (Scheme 1A).
tive oxidative C(sp3)—H amination of methylarenes still suffered
On the other hand, only a few examples have been reported
through double/triple C(sp3)—H functionalization of benzylic
from some limitations. Oxidative state amine, amide and aniline
bearing strong electron-withdrawing groups were mostly applied
to this transformation. On the contrary, simple anilines and elec-
C(sp3)—H bonds to construct C—F/C—B bonds by Chen,[7] Tang,[8]
Baxter,[9] and Chirik,[10] et al. (Scheme 1A). In addition, a series of
tron-rich anilines could be hard to transform to the desired prod-
ucts since they were easy to suffer from oxidation or homodimeri-
zation.[23] On the other hand, only a few examples of building
C(sp3)—S bonds were reported by Lei,[24] Qing,[25] Wu,[26] and
Bolm.[27]
elegant methods were successfully applied to construct C=O, C=C,
and C=N double bonds (Scheme 1B). The direct oxidation of ben-
zylic C(sp3)—H bond to aryl ketone was the most common.[11-16] In
2012, Zhang[17] and Patel[18] accomplished a Pd-catalyzed benzylic
C(sp3)—H arylation/oxidation reaction. Later, Li[19] developed a
Scheme 1 C—H Functionalization of Methylarenes
*E-mail: jianghf@scut.edu.cn
For submission: https://mc.manuscriptcentral.com/cjoc
For articles: https://onlinelibrary.wiley.com/journal/16147065
† Dedicated to the 30th Anniversary of State Key Laboratory of Organome-
tallic Chemistry.
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Chin. J. Chem. 2019, 37, 1158－1166

Direct Access to 2-Arylbenzothiazoles
Chin. J. Chem.
Aryl-substituted benzothiazoles, especially for 2-arylbenzothi-
azoles, are one of the most important heterocycles, which have
been extensively investigated for applications in bioactive natural
compounds, important drugs and advanced functional materials
(Scheme 2).[28] Previous studies for the synthesis of 2-arylbenzo-
thiazoles mainly focused on: (i) condensation of 2-aminobenzene-
thiols with aldehydes, ketones, alcohols, carboxylic acids, or ni-
triles;[29] (ii) direct arylation of benzothiazoles[30] or (iii) intramo-
lecular cyclization of thiobenzanilides,[31] and (iiii) three-compo-
nent annulations.[32] Itoh,[33] Ma,[34] Sekar,[35] Liang,[36] and Lee[37]
et al. developed an efficient synthesis of benzothiazoles using
2-haloanilides and thiol surrogates via palladium- or copper-cata-
lyzed double C—N/C—S bond formation (Schemes 2A and 2B). We
have also developed an efficient protocol for the synthesis of
benzothiazoles by C C triple bond cleavage of the alkyne moiety
(Scheme 2C).[38] Noteworthily, Wei reported a simple synthetic
strategy with methylaromatics, aniline, and elemental sulfur at
275 °C .[32f] Deng has developed a novel oxidative approach for the
synthesis of 2-arylbenzothiazoles from aromatic amines, benzal-
dehydes, and elemental sulfur.[32b] Inspired by these works, we
speculated that direct transformation of methylarenes via C—H
functionalization of benzylic C(sp3)—H bonds under Cu/[O] cata-
lytic system should provide an atom- and step-economic strategy
to construct benzothiazole products. Herein, we report a cop-
per-catalyzed oxidative annulation through benzylic C(sp3)—H of
methylarenes with 2-iodoaniline and potassium sulfide (Scheme
2D).
S1).
Table 1 Optimization of reaction conditionsa
Entry
Catalyst
Oxidant
Additive
Solvent
Yieldb/%
1
2
CuI
CuI
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
TBHP
DDQ
—
—
Trace
35
—
DMF
3
CuI
—
DMSO
MeCN
DCE
61
4
CuI
—
—
NR
NR
50
5
CuI
6
CuBr2
CuCl2
CuBr
Cu(OTf)2
CuCl2
CuCl2
CuCl2
CuCl2
CuCl2
CuCl2
CuCl2
CuCl2
CuCl2
—
—
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
7
—
66
8
—
30
9
—
57
10
11
12
13
14
15
16
17
18c
19c
—
48
—
44
H2O2
—
32
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
Li2CO3
LiBr
75
66
Scheme 2 Methylarenes methods for the synthesis of benzothiazole
K2CO3
tBuOLi
DABCO
Li2CO3/H2O
Li2CO3/H2O
33
18
35
82 (79)
8
a Reaction conditions: 1a (0.20 mmol), 2 (0.60 mmol), 3a (2 mL), catalyst
(0.04 mmol), oxidant (0.40 mmol) and additive (0.30 mmol) for 12 h in the
indicated solvent (1.0 mL). b Determined by GC-MS using dodecane as the
internal standard. The value in parentheses is the isolated yield. c 20.0
equiv of H2O. DTBP = di-tert-butyl peroxide. TBHP = tert-butyl hydroper-
oxide. DDQ = 2,3-dicyano-5,6-dichlorobenzoquinone. DABCO = 1,4-diaza-
bicyclo[2.2.2]octane.
With the optimal reaction conditions in hand, the scope for
the synthesis of 2-substituted benzothiazoles 4 was then investi-
gated, and the results are summarized in Table 2. The study of the
substituent effect on the aryl rings of the 2-iodoaniline derivatives
showed that both electron-donating groups, such as 4-methyl,
4-methoxy, 5-methoxy (4ba, 4ca, 4ka), and electron-withdrawing
groups, such as halo, COOCH3, CF3, NO2, and CN (4da—4ja,
4la—4na) were all compatible with this catalytic system and
transformed to the desired products in moderate to excellent
yields. Meanwhile, the reactions of the 2-iodoaniline substrates
bearing two substituents gave the desired products (4oa—4qa) in
good yields. Other variants such as 3-iodopyridin-4-amine and
3-iodopyridin-2-amine could also provide the expected products
in 61% and 45% yields, respectively (4ra, 4sa).
To further examine the scope and limitations of the reaction,
various toluene analogues were tested as the substrates for the
reaction. As shown in Table 3, the reaction of p-xylene with
2-iodoaniline afforded 88% yield of the desired product (4ab). The
substrates 3 possessing halo group, such as fluoro, chrolo and
bromine, could be transformed smoothly and obtained the prod-
ucts in good yields (4ad—4af). However, the toluene bearing
strong electron-donating/withdrawing groups, such as OCH3, CF3,
CN, at the phenyl ring only gave moderate yields (4ac, 4ag, 4ah).
Then, the steric hindrance effects in aromatics were examined.
Results and Discussion
Our work was initiated with the reaction of 2-iodoaniline (1a),
potassium sulfide (2) and toluene (3a) in the presence of CuI and
DTBP (Table 1, entry 1). After 12 h, although only a slight of the
desired product 4aa was detected by using toluene as the sole
solvent, we were pleased to find that the direct C(sp3)—H amina-
tion of toluene was afforded. Then, a series of mixed solvents
were tested, which revealed that DMSO was the most efficient
(entries 2—5). Next, examination of various copper salts revealed
that CuCl2 was the most suitable catalyst, which could improve
the reaction efficiency (entries 6—9). Further evaluation of oxi-
dants, such as TBHP, DDQ, and H2O2, indicated DTBP was the best
choice (entries 10—12). Different additives were also investigated,
and the product was formed in 82% yield in the presence of
Li2CO3 and H2O (entries 13—18). Control experiments revealed
that copper was beneficial to this transformation (entry 19).
Reaction temperature, raw ration, and more detailed investiga-
tion on the yields were displaced in Supporting Information (Table
Chin. J. Chem. 2019, 37, 1158－1166
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Concise Report
Table 2 Scope of o-Iodoanilinesa
a Reaction conditions: 1 (0.20 mmol), 2 (0.60 mmol), 3 (2 mL), CuCl2 (0.04 mmol), DTBP (0.40 mmol) Li2CO3 (0.30 mmol) and H2O (4 mmol) in 1.0 mL of
DMSO at 160 oC for 12h. b Without H2O. c 24 h.
Table 3 Scope of methylarenesa
a Reaction conditions: 1a (0.20 mmol), 2 (0.60 mmol), 3 (2 mL), CuCl2 (0.04 mmol), DTBP (0.40 mmol) Li2CO3 (0.30 mmol) and H2O (4 mmol) in 1.0 mL of
DMSO at 160 oC for 12h. b 3 (1 mL). c 24 h.
The reaction of o-xylene (4ai) and m-xylene (4aj) gave the desired
products in moderate yields. These results indicated the steric and
electronic effects affected the product formation. 4-Methylpyri-
dine and 2-methylthiophene were also tolerated in the reaction,
and the desired products 4ak and 4al were isolated in the yields
of 43% and 62%, respectively.
To gain more insights into the mechanism of this transforma-
tion, a series of control experiments were then performed
(Scheme 3). Without 2-iodoaniline 1a, the treatment of toluene
3a and potassium sulfide 2 under the standard conditions could
not afford the benzaldehyde 5 and benzyl alcohol 6 (Scheme 3a).
Furthermore, no product was observed using 2-aminothiophenol
7 instead of 2-iodoaniline 1a and potassium sulfide 2 (Scheme 3d).
These results indicated that benzaldehyde, benzyl alcohol or
2-aminothiophenol should not be the intermediate of this process.
When the reaction was conducted with toluene as the sole sol-
vent, the C(sp3)—H adjacent to nitrogen product 8 was detected.
Moreover, the product 8 was then smoothly transferred into the
final benzothiazole under the standard conditions (Schemes 3e
and 3f). Therefore, we speculated that the N-benzyl-2-iodoaniline
8 might be a key intermediate.
Based on these observations, a tentative mechanism for the
product formation is proposed in Scheme 4. Initially, the
tert-butoxyl radical is generated from DTBP.[39] Then, the
tert-butoxyl radical abstracts the hydrogen atom of toluene to
afford benzyl radical A.[39] A single-electron transfer (SET) from A
to copper(II) leads to cation B and copper(I), which can be oxi-
dized to copper(II) for catalytic recycle by DTBP.[24,40] Next, the
nucleophilic reaction of amine 1 with the benzyl cation B forms
products C and D.[2a] Subsequently, E is formed via an inter-
molecular nucleophilic attack with K2S.[32d,41] Next, oxidative addi-
tion and ligand exchange with CuII species produce a putative CuIII
intermediate F.[42] Finally, reductive elimination affords the de-
sired product. Meanwhile, the CuI can be oxidized to regenerate
the CuII species.
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Direct Access to 2-Arylbenzothiazoles
Chin. J. Chem.
Scheme 3 Control experiments
Scheme 4 Proposed mechanism
General procedure for the synthesis of benzo[d]thiazole
Conclusions
products 4
In summary, we have developed a novel Cu-catalyzed oxida-
tive annulation of o-iodoanilines, potassium sulfide and methyl-
arenes. Through this method, benzylic C(sp3)—H bonds of methyl-
arenes were transferred into C—N/C—S bonds. This method tol-
erated a wide range of functional groups and provided an effec-
tive approach to synthesize 2-arylbenzothiazoles. Mechanistic
studies revealed that C(sp3)—H amination of methylarenes should
be a key path.
A 25 mL dried Schlenk tube was added the mixture of
2-iodoaniline 1a (0.20 mmol), K2S 2 (0.60 mmol), toluene 3a (2.0
mL), CuI (0.04 mmol), Li2CO3 (0.30 mmol), DTBP (0.4 mmol) and
H2O (4 mmol) in DMSO (1.0 mL) successively. The reaction was
then allowed to stir at 160 °C for 12 h. Upon completion, the reac-
tion mixture was washed by saturated NaCl aqueous solution
(2×10 mL) and then extracted with ethyl acetate (2×10 mL), and
the organic layers were combined, dried over anhydrous MgSO4,
filtered, and concentrated under reduced pressure. The residue
was separated by column chromatography (petroleum ether/ethyl
acetate 10 : 1—50 : 1) to give the pure products.
Experimental
General information
2-Phenylbenzo[4,5]thieno[3,2-d]thiazole (3aa).[38] White solid;
Unless otherwise stated, all reagents and solvents were pur-
chased from commercial suppliers and used without further puri-
1
mp 134—136 °C ; H NMR (400 MHz, CDCl3) δ: 8.29 (d, J = 8.0 Hz,
1H), 8.06 (d, J = 6.8 Hz, 2H), 7.84 (d, J = 8.0 Hz, 1H), 7.61—7.36 (m,
5H); 13C NMR (101 MHz, CDCl3) δ: 170.6, 156.2, 142.8, 134.1,
130.9, 130.6, 130.3, 129.1, 126.6, 125.1, 125.1, 123.3, 121.9; IR
(KBr) νmax: 3046, 2918, 1464, 1266, 1223, 748, 669 cm–1; HRMS
(ESI): calcd for C15H10NS2 [M+H]+: 268.0249, found: 268.0250.
2-Phenylbenzo[d]thiazole (4aa).[38] White solid (33 mg, 79%);
mp 113—114 °C ; 1H NMR (400 MHz, CDCl3) δ: 8.12—8.05 (m, 3H),
7.91 (d, J = 7.8 Hz, 1H), 7.70—7.50 (m, 4H), 7.41—7.31 (m, 1H).
13C NMR (100 MHz, CDCl3) δ: 168.1, 154.0, 135.0, 133.6, 131.0,
1
fication. H NMR and 13C NMR spectra were recorded at 400 MHz
NMR spectrometer using CDCl3 as solvent and TMS as an internal
standard. IR spectra were obtained with an infrared spectrometer
on either potassium bromide pellets or liquid films between two
potassium bromide pellets. GC−MS data were obtained using
electron ionization. HRMS was carried out on a high-resolution
mass spectrometer (LCMS-IT-TOF). Melting points were measured
using a melting point instrument and were uncorrected.
Chin. J. Chem. 2019, 37, 1158－1166
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129.0, 127.6, 126.3, 125.2, 123.2, 121.6. IR (KBr) νmax: 3015, 1661,
1455 964, 798, 677 cm–1; MS (EI, 70 eV): m/z (%) = 211 [M]+, 184,
167, 108, 82, 69.
2-Phenylbenzo[d]thiazole-6-carbonitrile (4ja).[31d] Yellow solid
(32 mg, 69%); mp 197—198 °C ; H NMR (400 MHz, CDCl3) δ: 8.22
1
(s, 1H), 8.12—8.09 (m, 3H), 7.72 (d, J = 8.5 Hz, 1H), 7.58—7.48 (m,
3H). 13C NMR (100 MHz, CDCl3) δ: 172.2, 156.4, 135.4, 132.6,
132.0, 129.5, 129.2, 127.8, 126.3, 123.8, 118.7, 108.5; IR (KBr) νmax
2923, 2228, 1647, 1463, 1260, 965, 831, 755, 675 cm–1; MS (EI, 70
eV): m/z (%) = 236 [M]+, 209, 164, 133, 104, 82, 69.
6-Methyl-2-phenylbenzo[d]thiazole (4ba).[38] White solid (35
mg, 77 %); mp 125—126 °C ; 1H NMR (400 MHz, CDCl3) δ: 8.08 (dd,
J = 6.6, 2.7 Hz, 2H), 7.96 (d, J = 8.3 Hz, 1H), 7.69 (s, 1H), 7.51—7.45
(m, 3H), 7.30 (d, J = 8.3 Hz, 1H), 2.50 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ: 167.0, 152.3, 135.3, 135.2, 133.8, 130.7, 128.9, 127.9,
127.4, 122.7, 121.3, 21.5. IR (KBr) νmax: 2992, 2888, 1662, 1558,
1456, 961, 758, 677 cm–1; MS (EI, 70 eV): m/z (%) = 225 [M]+, 209,
180, 148, 121, 112, 77.
:
5-Methyl-2-phenylbenzo[d]thiazole (4ka).[38] White solid (33
mg, 73%); mp 145—146 °C ; 1H NMR (400 MHz, CDCl3) δ:
8.13—8.04 (m, 2H), 7.89 (s, 1H), 7.77 (d, J = 8.2 Hz, 1H),
7.53—7.46 (m, 3H), 7.22 (d, J = 8.2 Hz, 1H), 2.52 (s, 3H). 13C NMR
(100 MHz, CDCl3) δ: 168.2, 154.5, 136.4, 133.7, 132.0, 130.8,
129.0, 127.5, 126.8, 123.2, 121.1, 21.5; IR (KBr) νmax: 3058, 1658,
6-Methoxy-2-phenylbenzo[d]thiazole (4ca).[38] White solid
(31 mg, 65%); mp 116—117 °C ; 1H NMR (400 MHz, CDCl3) δ:
8.07—8.00 (m, 2H), 7.96 (d, J = 8.9 Hz, 1H), 7.50—7.43 (m, 3H),
7.34 (d, J = 2.0 Hz, 1H), 7.10—7.08 (m, 1H), 3.87 (s, 3H). 13C NMR
(100 MHz, CDCl3) δ: 165.5, 157.8, 148.6, 136.4, 133.7, 130.5,
128.9, 127.2, 123.7, 115,6, 104.1, 55.7. IR (KBr) νmax: 3035, 1423,
1244, 959, 844, 763, 677 cm–1; MS (EI, 70 eV): m/z (%) = 241 [M]+,
226, 198, 171, 120, 95, 77.
1454, 1250, 954, 762, 683 cm–1; MS (EI, 70 eV): m/z (%) = 225 [M]+,
209, 193, 165, 121, 112, 77.
5-Fluoro-2-phenylbenzo[d]thiazole (4la).[32a] White solid (32
mg, 69%); mp 111—112 °C ; 1H NMR (400 MHz, CDCl3) δ: 8.08 (dd,
J = 6.5, 2.8 Hz, 2H), 7.82 (dd, J = 8.8, 5.1 Hz, 1H), 7.75 (dd, J = 9.5,
2.3 Hz, 1H), 7.55—7.46 (m, 3H), 7.18—7.13 (m, 1H). 13C NMR (100
MHz, CDCl3) δ: 170.5, 162.0 (d, J = 241 Hz), 155.1 (d, J = 12 Hz),
133.4, 131.3, 130.5, 129.1, 127.5, 122.2 (d, J = 10 Hz), 113.9 (d, J =
25 Hz), 109.4 (d, J = 24 Hz); IR (KBr) νmax: 1560, 1455, 1240, 1138,
955, 876, 760, 681 cm–1; MS (EI, 70 eV): m/z (%) = 229 [M]+, 202,
185, 126, 114, 93, 69.
6-Fluro-2-phenylbenzo[d]thiazole (4da).[38] White solid (32
1
mg, 70%); mp 134—135 °C ; H NMR (400 MHz, CDCl3) δ: 8.06 (m,
2H), 8.01 (m, 1H), 7.58 (m, 1H), 7.55—7.43 (m, 3H), 7.26—7.19 (m,
1H). 13C NMR (100 MHz, CDCl3) δ: 167.8, 160.5 (d, J = 244 Hz),
150.8, 136.0 (d, J = 11 Hz), 133.4, 131.0, 129.0, 127.4, 124.1 (d, J =
10 Hz), 114.9 (d, J = 24Hz), 107.8 (d, J = 26 Hz); IR (KBr) νmax: 1661,
1468, 1290, 956, 832, 674 cm–1; MS (EI, 70 eV): m/z (%) = 229 [M]+,
202, 185, 152, 126, 101, 82, 69.
5-Chloro-2-phenylbenzo[d]thiazole (4ma).[38] White solid (30
mg, 62%); mp 135—136 °C ; 1H NMR (400 MHz, CDCl3) δ:
8.11—8.02 (m, 3H), 7.79 (d, J = 8.5 Hz, 1H), 7.50 (d, J = 4.6 Hz, 3H),
7.35 (d, J = 8.5 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ: 169.9, 155.0,
133.3, 133.2, 132.3, 131.3, 129.1, 127.6, 125.6, 123.0, 122.3; IR
(KBr) νmax: 2889 IR (KBr) νmax: 1266, 959, 756, 676 cm–1; MS (EI, 70
eV): m/z (%) = 245 [M]+, 210, 142, 122, 107, 77, 69, 63.
6-Chloro-2-phenylbenzo[d]thiazole (4ea).[29d] White solid (33
mg, 68%); mp 150—151 °C ; 1H NMR (400 MHz, CDCl3) δ:
8.08—8.06 (m, 2H), 7.98 (d, J = 8.7 Hz, 1H), 7.87 (d, J = 1.6 Hz, 1H),
7.54—7.47 (m, 3H), 7.46—7.44 (m, 1H). 13C NMR (100 MHz, CDCl3)
δ: 168.5, 152.7, 136.2, 133.2, 131.2, 131.1, 129.1, 127.5, 127.1,
123.9, 121.2; IR (KBr) νmax: 3069, 1650, 1472, 1288, 959, 825, 756,
674 cm–1; MS (EI, 70 eV): m/z (%) = 245 [M]+, 218, 209, 142, 107,
69.
5-Bromo-2-phenylbenzo[d]thiazole (4na).[31d] White solid (32
1
mg, 55%); mp 136—137 °C ; H NMR (400 MHz, CDCl3) δ: 8.22 (s,
1H), 8.10—8.03 (m, 2H), 7.74 (d, J = 8.5 Hz, 1H), 7.55—7.44 (m,
4H). 13C NMR (100 MHz, CDCl3) δ: 169.7, 155.3, 133.8, 133.2,
131.3, 129.1, 128.3, 127.6, 126.1, 122.6, 119.9; IR (KBr) νmax: 3072,
1719, 1457, 1255, 961, 880, 747, 690 cm–1; MS (EI, 70 eV): m/z (%)
= 289 [M]+, 210, 188, 146, 108, 77, 69, 63.
6-Bromo-2-phenylbenzo[d]thiazole (4fa).[38] White solid (38
mg, 66%); mp 157—158 °C ; 1H NMR (400 MHz, CDCl3) δ:
8.07—8.05 (m, 2H), 8.00 (d, J = 1.7 Hz, 1H), 7.90 (d, J = 8.7 Hz, 1H),
7.59—7.56 (m, 1H), 7.50—7.48 (m, 3H). 13C NMR (100 MHz, CDCl3)
δ: 168.5, 153.0, 136.6, 133.1, 131.2, 129.8, 129.1, 127.5, 124.3,
124.1, 118.7; IR (KBr) νmax: 3064, 1650, 1473, 1298, 1230, 959, 820,
753, 676 cm–1; MS (EI, 70 eV): m/z (%) = 289 [M]+, 210, 188, 144,
107, 77, 69.
4,6-Dimethyl-2-phenylbenzo[d]thiazole (4oa).[32a] White solid
(37 mg, 78%); mp 85—86 °C ; 1H NMR (400 MHz, CDCl3) δ: 8.10 (d,
J = 6.6 Hz, 2H), 7.55—7.43 (m, 4H), 7.11 (s, 1H), 2.78 (s, 3H), 2.46
(s, 3H). 13C NMR (100 MHz, CDCl3) δ: 165.6, 151.6, 135.2, 135.1,
134.1, 132.7, 130.5, 128.9, 128.5, 127.4, 118.7, 21.5, 18.3; IR (KBr)
νmax: 3040, 2921, 1666, 1593, 1451, 1320, 12131, 962, 755, 683
cm–1; MS (EI, 70 eV): m/z (%) = 239 [M]+, 224, 206, 135, 121, 91,
77.
Methyl 2-phenylbenzo[d]thiazole-6-carboxylate (4ga).[31d]
1
White solid (34 mg, 64%); mp 159—160 °C ; H NMR (400 MHz,
4,6-Dichloro-2-phenylbenzo[d]thiazole (4pa).[38] White solid
CDCl3) δ: 8.62 (s, 1H), 8.19—8.07 (m, 4H), 7.51 (d, J = 5.5 Hz, 3H),
3.97 (s, 3H). 13C NMR (100 MHz, CDCl3) δ: 171.5, 166.6, 157.0,
134.9, 133.1, 131.6, 129.1, 127.7, 127.5, 126.9, 123.8, 122.8, 52.3;
IR (KBr) νmax: 3216, 1708, 1453, 1271, 1109, 965, 759 cm–1; MS (EI,
70 eV): m/z (%) = 269 [M]+, 238, 210, 183, 166, 108, 63.
1
(42 mg, 75%); mp 152—153 °C ; H NMR (400 MHz, CDCl3) δ: 8.10
(d, J = 6.4 Hz, 2H), 7.77 (s, 1H), 7.54—7.46 (m, 4H). 13C NMR (100
MHz, CDCl3) δ 169.2, 149.9, 137.1, 132.9, 131.6, 130.9, 129.1,
128.5, 127.8, 127.1, 119.8; IR (KBr) νmax: 3076, 1710, 1560, 1446,
1257, 962, 858, 757, 676 cm–1; MS (EI, 70 eV): m/z (%) = 279 [M]+,
244, 209, 176, 141, 106, 97, 77.
2-Phenyl-6-(trifluoromethyl)benzo[d]thiazole (4ha).[38] Yellow
solid (45 mg, 80%); mp 160—161 °C ; 1H NMR (400 MHz, CDCl3) δ:
8.17 (s, 1H), 8.13 (d, J = 8.6 Hz, 1H), 8.11—8.04 (m, 2H), 7.72 (d,
J = 8.6 Hz, 1H), 7.56—7.45 (m, 3H). 13C NMR (100 MHz, CDCl3) δ:
171.0, 156.0, 135.0, 132.9, 131.6, 129.1, 127.7, 142.2 (q, J = 32
Hz), 124.2 (q, J = 271 Hz), 123.4, 123.2 (q, J = 3 Hz), 119.2 (q, J = 4
Hz); IR (KBr) νmax: 2890, 1663, 1474, 1307, 1111, 962, 838, 756,
677 cm–1; MS (EI, 70 eV): m/z (%) = 279 [M]+, 260, 210, 176, 157,
132, 77, 69.
6-Chloro-4-fluoro-2-phenylbenzo[d]thiazole (4qa).[38] Yellow
solid (30 mg, 57%); mp 156—158 °C ; 1H NMR (400 MHz, CDCl3) δ:
8.06 (m, 2H), 7.61 (s, 1H), 7.49 (m, 3H), 7.19 (m, 1H). 13C NMR
(100 MHz, CDCl3) δ: 168.9, 155.1 (d, J = 259 Hz), 141.7 (d, J = 13
Hz), 138.2 (d, J = 4 Hz), 132.7, 131.5, 131.0 (d, J = 9 Hz), 129.0,
127.7, 117.1 (d, J = 5 Hz), 113.5 (d, J = 21 Hz); IR (KBr) νmax: 3078,
1561, 1437, 1234, 982, 840, 757, 678 cm–1; MS (EI, 70 eV): m/z (%)
= 263 [M]+, 236, 227, 160, 125, 81, 69.
6-Nitro-2-phenylbenzo[d]thiazole (4ia).[31d] Yellow solid (31
1
2-Phenylthiazolo[5,4-c]pyridine (4ra).[38] White solid ( 26 mg,
mg, 61%); mp 191—193 °C ; H NMR (400 MHz, CDCl3) δ: 8.82 (s,
1
1H), 8.36 (d, J = 9.0 Hz, 1H), 8.13—8.10 (m, 3H), 7.59—7.51 (m,
3H). 13C NMR (100 MHz, CDCl3) δ: 173.7, 157.8, 144.9, 135.3,
132.7, 132.2, 129.3, 127.9, 123.3, 121,9, 118.2; IR (KBr) νmax: 2997,
1655, 1514, 1328, 956, 843, 755, 676 cm–1; MS (EI, 70 eV): m/z (%)
= 256 [M]+, 226, 210, 198, 183, 139, 107, 95, 77.
61%); mp 136—137 °C ; H NMR (400 MHz, CDCl3) δ: 9.18 (s, 1H),
8.64 (d, J = 5.6 Hz, 1H), 8.19—8.04 (m, 2H), 7.91 (d, J = 5.6 Hz, 1H),
7.59—7.43 (m, 3H). 13C NMR (100 MHz, CDCl3) δ: 173.3, 158.8,
145.9, 144.1, 132.7, 132.1, 132.0, 129.2, 128.0, 117.3; IR (KBr) νmax
:
3031, 1659, 1550, 1462, 1242, 963, 841, 764, 649 cm–1; MS (EI, 70
1162
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Chin. J. Chem. 2019, 37, 1158－1166

Direct Access to 2-Arylbenzothiazoles
Chin. J. Chem.
eV): m/z (%) = 212 [M]+, 185, 168, 140, 109, 82, 77.
mp 37—38 °C ; 1H NMR (400 MHz, CDCl3) δ: 8.12 (d, J = 8.2 Hz, 1H),
7.93 (d, J = 7.9 Hz, 1H), 7.77 (d, J = 7.5 Hz, 1H), 7.56—7.52 (m, 1H),
7.44—7.28 (m, 4H), 2.67 (s, 3H). 13C NMR (100 MHz, CDCl3) δ:
168.0, 153.7, 137.2, 135.6, 133.1, 131.5, 130.5, 130.0, 126.1,
2-Phenylthiazolo[5,4-b]pyridine (4sa). White solid (19 mg,
1
45%); mp 126—127 °C ; H NMR (400 MHz, CDCl3) δ: 8.72 (d, J =
4.4 Hz, 1H), 8.24 (d, J = 8.0 Hz, 1H), 8.21—8.12 (m, 2H),
7.58—7.46 (m, 3H), 7.33—7.26 (m, 1H). 13C NMR (100 MHz, CDCl3) 126.0, 125.1, 123.3, 121.3, 21.3; IR (KBr) νmax: 3061, 2928, 1851,
δ: 171.2, 164.7, 148.4, 133.0, 131.8, 130.5, 129.0, 128.6, 127.6,
119.8; IR (KBr) νmax: 3051, 1655, 1471, 1379, 1242, 961, 773, 688
cm–1; HRMS-ESI (m/z): calcd for C12H9N2S, [M+H]+ : 213.0481,
found, 213.0482.
1658, 1446, 1297, 1220, 955, 752 cm–1; MS (EI, 70 eV): m/z (%) =
225 [M]+, 209, 190, 165, 116, 112, 91, 82, 69.
2-(m-Tolyl)benzo[d]thiazole (4aj).[30e] Yellow solid (23 mg,
1
50%); mp 68—69 °C ; H NMR (400 MHz, CDCl3) δ: 8.12 (d, J = 8.2
2-(p-Tolyl)benzo[d]thiazole (4ab).[38] Yellow solid (40 mg,
Hz, 1H), 7.93 (d, J = 7.9 Hz, 1H), 7.77 (d, J = 7.5 Hz, 1H), 7.56—7.50
(m, 1H), 7.44—7.28 (m, 4H), 2.67 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ: 168.3, 154.0, 138.8, 135.0, 133.5, 131.8, 128.9, 128.0,
126.3, 125.1, 124.8, 123.1, 121.6, 21.3; IR (KBr) νmax: 3054, 2925,
1684, 1595, 1459, 1304, 1250, 976, 758 cm–1; MS (EI, 70 eV): m/z
(%) = 225 [M]+, 209, 190, 165, 116, 112, 91, 82, 69.
1
88%); mp 85—86 °C ; H NMR (400 MHz, CDCl3) δ: 8.07 (d, J = 8.2
Hz, 1H), 7.99 (d, J = 8.1 Hz, 2H), 7.89 (d, J = 7.9 Hz, 1H), 7.51—7.45
(m, 1H), 7.37 (dd, J = 11.2, 4.0 Hz, 1H), 7.29 (d, J = 8.0 Hz, 2H),
2.42 (s, 3H). 13C NMR (100 MHz, CDCl3) δ: 168.2, 154.1, 141.4,
134.9, 130.9, 129.7, 127.5, 126.2, 125.0, 123.0, 121.5, 21.5; IR
(KBr) νmax: 3049, 2925, 1473, 1300, 1241, 961, 823, 750 cm–1; MS
(EI, 70 eV): m/z (%) = 225 [M]+, 210, 165, 112, 108, 91, 82, 69.
2-(4-Methoxyphenyl)benzo[d]thiazole (4ac).[38] White solid
(26 mg, 55%); mp 120—122 °C ; 1H NMR (400 MHz, CDCl3) δ:
8.09—8.00 (m, 3H), 7.86 (d, J = 8.0 Hz, 1H), 7.49—7.45 (m, 1H),
7.36—7,33 (m, 1H), 6.99 (d, J = 8.7 Hz, 2H), 3.86 (s, 3H). 13C NMR
(100 MHz, CDCl3) δ: 167.8, 161.9, 154.1, 134.8, 129.1, 126.3,
126.2, 124.8, 122.8, 121.5, 114.3, 55.4; IR (KBr) νmax: 3069, 2942,
2835, 1594, 1426, 1248, 1171, 958, 833, 750 cm–1; MS (EI, 70 eV):
m/z (%) = 241 [M]+, 226, 198, 154, 121, 106, 82, 69.
2-(Pyridin-4-yl)benzo[d]thiazole (4ak).[29d] White solid (18 mg,
1
43%); mp 166—167 °C ; H NMR (400 MHz, CDCl3) δ: 8.78 (s, 2H),
8.13 (d, J = 8.1 Hz, 1H), 7.95 (d, J = 5.7 Hz, 3H), 7.57—7.53 (m, 1H),
7.46 (t, J = 7.5 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ: 165.0, 154.0,
150.6, 140.6, 135.2, 126.8, 126.2, 123.9, 121.8, 121.2; IR (KBr) νmax
3047, 2925, 1598, 1472, 1414, 1314, 1249, 969, 828, 750 cm–1;
MS (EI, 70 eV): m/z (%) = 212 [M]+, 186, 141, 108, 82, 69.
:
2-(Thiophen-2-yl)benzo[d]thiazole (4al).[38] White solid (27
1
mg, 62%); mp 101—103 °C ; H NMR (400 MHz, CDCl3) δ: 8.04 (d,
J = 8.2 Hz, 1H), 7.84 (d, J = 8.0 Hz, 1H), 7.66 (d, J = 3.5 Hz, 1H),
7.48 (dd, J = 14.7, 6.5 Hz, 2H), 7.38—7.34 (m, 1H), 7.14—7.12 (m,
1H). 13C NMR (100 MHz, CDCl3) δ: 161.4, 153.6, 137.2, 134.6,
129.3, 128.6, 128.0, 126.4, 125.2, 122.9, 121.4; IR (KBr) νmax: 3073,
2929, 1645, 1429, 1290, 910, 837, 731 cm–1; MS (EI, 70 eV): m/z
(%) = 217 [M]+, 184, 173, 146, 108, 82, 69.
2-(4-Fluorophenyl)benzo[d]thiazole (4ad).[29d] Yellow solid (35
mg, 78%); mp 99—100 °C ; 1H NMR (400 MHz, CDCl3) δ:
8.13—8.02 (m, 3H), 7.89 (d, J = 8.0 Hz, 1H), 7.51—7.48 (m, 1H),
7.40—7.37 (m, 1H), 7.20—7.16 (m, 2H). 13C NMR (100 MHz, CDCl3)
δ: 166.7, 164.4 (d, J = 250 Hz), 154.0, 135.0, 129.9 (d, J = 4 Hz),
129.5 (d, J = 9 Hz), 126.4, 125.2, 123.2, 121.6, 116.1 (d, J = 22 Hz);
IR (KBr) νmax: 3062, 2922, 1596, 1479 cm–1; MS (EI, 70 eV): m/z (%)
= 229 [M]+, 202, 185,114, 108, 82, 69, 63.
Supporting Information
The supporting information for this article is available on the
WWW under https://doi.org/10.1002/cjoc.201900340.
2-(4-Chlorophenyl)benzo[d]thiazole (4ae).[38] White solid (37
1
mg, 75%); mp 117—118 °C ; H NMR (400 MHz, CDCl3) δ: 8.07 (d,
J = 8.2 Hz, 1H), 8.02 (d, J = 8.5 Hz, 2H), 7.90 (d, J = 8.0 Hz, 1H),
7.54—7.43 (m, 3H), 7.40 (t, J = 7.6 Hz, 1H). 13C NMR (100 MHz,
CDCl3) δ: 166.6, 154.0, 137.0, 135.0, 132.1 129.3, 128.7, 126.5,
125.4, 123.3, 121.6; IR (KBr) νmax: 3058, 1645, 1466, 1286, 1096,
962, 833, 741 cm–1; MS (EI, 70 eV): m/z (%) = 245 [M]+, 210, 122,
108, 82, 69.
Acknowledgement
The authors thank the National Key Research and Develop-
ment Program of China (No. 2016YFA0602900), the National Nat-
ural Science Foundation of China (No. 21420102003), and
Guangdong Province Science Foundation (No. 2017B090903003)
for financial support.
2-(4-Bromophenyl)benzo[d]thiazole (4af).[32a] White solid (40
1
mg, 70%); mp 126—127 °C ; H NMR (400 MHz, CDCl3) δ: 8.07 (d,
J = 8.2 Hz, 1H), 7.96 (d, J = 8.5 Hz, 2H), 7.90 (d, J = 8.0 Hz, 1H),
7.62 (d, J = 8.5 Hz, 2H), 7.52—7.48 (m, 1H), 7.42—7.38 (m, 1H).
13C NMR (100 MHz, CDCl3) δ: 166.7 154.0, 139.0, 135.0, 132.5,
132.2, 128.9, 126.5, 125.4, 123.3, 121.6; IR (KBr) νmax: 1651, 1473,
1251, 960, 832, 744 cm–1; MS (EI, 70 eV): m/z (%) = 289 [M]+, 210,
183, 145, 108, 105, 82, 69.
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White solid (24 mg, 43%); mp 158—159 °C ; H NMR (400 MHz,
CDCl3) δ: 8.20 (d, J = 8.0 Hz, 2H), 8.11 (d, J = 8.1 Hz, 1H), 7.93 (d,
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7.77 (d, J = 8.0 Hz, 2H), 7.55—7.51 (m, 1H), 7.45—7.41 (m, 1H).
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:
3062, 2225, 1471, 1256, 961, 835, 754; MS (EI, 70 eV): m/z (%) =
236 [M]+, 207, 118, 108, 82, 69, 63.
2-(o-Tolyl)benzo[d]thiazole (4ai).[29f] Yellow solid (20 mg, 45%);
Chin. J. Chem. 2019, 37, 1158－1166
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www.cjc.wiley-vch.de
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Yu, Wu & Jiang
Concise Report
2016, 18, 1526–1529.
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Manuscript received: August 23, 2019
Manuscript revised: September 11, 2019
Manuscript accepted: September 12, 2019
Accepted manuscript online: September 29, 2019
Version of record online: October 4, 2019
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Chin. J. Chem. 2019, 37, 1158－1166