Oxidant/Solvent-Controlled I2-Catalyzed Domino Annulation for Selective Synthesis of 2-Aroylbenzothiazoles and 2-Arylbenzothiazoles under Metal-Free Conditions

Article abstract of DOI:10.1021/acs.joc.0c02095

A simple and practical domino protocol for the selective synthesis of 2-aroylbenzothiazoles and 2-aryl benzothiazoles catalyzed by I2 is developed under metal-free conditions. The reaction outcomes are exclusively controlled by the reaction oxidant/medium. With DMSO employed as both the solvent and the oxidant, an oxidation of aromatic methyl ketones takes precedence over the condensation with 2-aminobenzenethiols. On the other hand, when the reaction was carried out in PhNO2 or in 1,4-dioxane containing PhNO2, the condensation of aromatic methyl ketones with 2-aminobenzenethiols has priority to form imines which is followed by an oxidation of the methyl group from ketones to afford 2-arylbenzothiazoles as a sole product. The PhNO2/I2 co-catalytic system is proposed first time.

Full text of DOI:10.1021/acs.joc.0c02095

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Article
Oxidant/Solvent-Controlled I2‑Catalyzed Domino Annulation for
Selective Synthesis of 2‑Aroylbenzothiazoles and
2‑Arylbenzothiazoles under Metal-Free Conditions
Renchao Ma, Yuxin Ding, Rener Chen, Zhiming Wang, Lei Wang, and Yongmin Ma*
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ABSTRACT: A simple and practical domino protocol for the
selective synthesis of 2-aroylbenzothiazoles and 2-aryl benzothia-
zoles catalyzed by I2 is developed under metal-free conditions. The
reaction outcomes are exclusively controlled by the reaction
oxidant/medium. With DMSO employed as both the solvent and
the oxidant, an oxidation of aromatic methyl ketones takes
precedence over the condensation with 2-aminobenzenethiols.
On the other hand, when the reaction was carried out in PhNO2 or
in 1,4-dioxane containing PhNO2, the condensation of aromatic
methyl ketones with 2-aminobenzenethiols has priority to form
imines which is followed by an oxidation of the methyl group from
ketones to afford 2-arylbenzothiazoles as a sole product. The
PhNO2/I2 co-catalytic system is proposed first time.
gen.8d Recently, Tan et al. developed a one-pot tandem
procedure for the synthesis of 2-substituted benzothiazoles
under an I2/TBHP system.13 For the synthesis of 2-
aroylbenzothiazole, the Wu’s group developed an I2/IBX-
mediated domino strategy from 2-aminobenzenethiol with
arylethenes, arylacetylene, 2-hydroxy-aromatic ketones, or
carbinols via phenylglyoxal intermediates.14 His group also
constructed a 2-aroylbenzothiazole skeleton from aromatic
methyl ketones and 2-aminobenzenethiols in the presence of
an excess of I2.8b However, most likely, a mixture of 2-aryl and
2-aroyl benzothiazole was generated in dimethyl sulfoxide
(DMSO) from these two starting materials.6e,8c,d Intrigued by
these findings, we attempted the reaction of 2-amino-
benzenethiols and aromatic methyl ketones to synthesize 2-
aroyl and 2-aryl benzothiazoles selectively. Interestingly, 2-
aroylbenzothiazoles were selectively afforded with a catalytic
amount of I2 in DMSO, while 2-aryl analogues were formed in
nitrobenzene catalyzed by I2 (Scheme 1c). To the best of our
knowledge, the PhNO2-mediated I2-catalyzed strategy has
never been reported. Herein, we would like to disclose our
preliminary results in this aspect.
INTRODUCTION
■
Benzothiazoles represent an important and abundant class of
fused heterocycles. Compounds containing the benzothiazole
motif have their wide occurrence in diverse pharmacological
agents,1 natural products,2 and synthetic intermediates.3 In
addition, the benzothiazole scaffold has been found frequently
in other molecules such as industrial dyes2a,4 and functional
materials.5 Consequently, the development of effective
methods for constructing the benzothiazole skeleton has
attracted considerable attention, and a number of versatile
methods have been developed in recent years. There are two
conventional synthetic methods adopted for the preparation of
this building block: one involves a condensation and
annulation of 2-aminobenzenethiol with aromatic alcohol,6
aldehydes,7 aromatic methyl ketones,8 benzoic acids/ben-
zoates/benzoic anhydrides,9 or nitriles10 (Scheme 1a); another
is a metal-catalyzed intramolecular annulation of arylthioben-
zamide analogues (Scheme 1b).11 However, these existing
methods suffer from the disadvantages of multistep processes,
use of stoichiometric oxidants, or low yields, all of which limit
their application in industrial production. Therefore, develop-
ment of practical and efficient procedures for the preparation
of 2-substituted benzothiazoles in a user-friendly manner is
highly desirable.
Received: August 31, 2020
In 2009, Ma et al. reported a practical synthesis of
substituted benzothiazoles from 2-haloanilides with sulfides
using CuI as the catalyst under mild conditions.12 Deng’s
group used 2-aminobenzenethiol and aryl ketones to
synthesize 2-arylbenzothiazoles promoted by molecular oxy-
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A

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Scheme 1. Literature Reports and the Present Work for the Synthesis of 2-Substituted Benzothiazoles
a
Table 1. Optimization of the Reaction Conditions
yield (%)
Entry
solvent
I2 (equiv)
temp. (oC)
3aa
4aa
1
2
3
4
DMSO
EtOH
MeOH
THF
1
1
1
1
110
80
65
82
0
0
0
0
0
65
0
0
5
6
7
8
DMF
DMA
PhCH3
1,4-dioxane
PhCl
PhNO2
PhNO2
PhNO2
DMSO
PhNO2
DMSO or PhNO2
1,4-dioxane + PhNO2
PhCl + PhNO2
DMF + PhNO2
DMA + PhNO2
PhCl + DMSO
1,4-dioxane + DMSO
1,4-dioxane + PhNO2
DMSO
1
1
1
1
1
1
0.3
0.1
0.1
0.1
0
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
80
0
0
0
0
0
0
0
0
77
0
0
0
0
0
0
0
0
0
0
0
0
9
0
10
11
12
13
80
77
78
0
75
0
80
15
0
b
14
15
16
17
18
19
20
21
22
23
24
c
c
c
c
0
d
48
15
0
0
0
d
c
0
51
42
80
60
DMSO
a
Reaction conditions: 1a (1.5 mmol), 2a (1 mmol), solvent (2 mL), and iodine at the indicated amount in a reaction vessel at the indicated
b
c
d
temperature for 2−8 h. Reaction under the N2 atmosphere. PhNO2 at 1 mmol (1 equiv). DMSO at 1 mmol (1 equiv).
B
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a
Table 2. Reaction of 2-Aminobenzenethiols with Various Ketones Mediated by DMSO
a
Reaction conditions: 1 (1.5 mmol), 2 (1 mmol), DMSO (2 mL), and iodine (10 mol %) in a reaction vessel at 110 °C for 2 h.
(entry 10). Upon decreasing the dose of I2 to 30 and 10%, the
yield of 4aa was not markedly influenced (entries 11−12).
Based on this finding, we attempted to reduce the dose of I2 to
10% for the reaction of acetophenone and 2-aminobenzene-
thiol in DMSO. To our delight, 77% yield of 3aa was afforded,
which is not significantly different from that of I2 at 1 equiv
(entry 13 vs 1). The reaction in PhNO2 was also successively
carried out under a N2 atmosphere, without significant loss of
the product yield, indicating that oxygen from air was not
involved in the oxidation process (entry 14). In the absence of
I2, the reaction did not proceed either in DMSO or in PhNO2,
suggesting that I2 played a crucial role in this transformation
(entry 15). Because PhNO2 possesses a high boiling point and
is difficult to be removed by a routine rotary evaporation, we
attempted to use 1,4-dioxane with 1 equiv of PhNO2 to replace
PhNO2 as the reaction medium and satisfactorily a slightly
RESULTS AND DISCUSSION
■
We began our study by choosing 2-aminobenzenethiol (1a)
and acetophenone (2a) as the initial starting materials and
investigating the effect of solvents on the product yield. Similar
to Wu’s work,8b when acetophenone reacted with 1.5 equiv of
2-aminobenzenethiol in DMSO in the presence of 1 equiv of I2
at 110 °C, 82% yield of the 2-aroylbenzothiazole (3aa) was
achieved (Table 1, entry 1). In contrast to DMSO, other
solvents such as ethanol, methanol, tetrahydrofuran (THF),
dimethylformamide (DMF), N,N-dimethylaniline (DMA),
toluene, 1,4-dioxane, and chlorobenzene failed to facilitate
the reaction and the desired product was not obtained (entries
2−9). Surprisingly, when the reaction was carried out in
nitrobenzene, the expected 2-aroylbenzothiazole was not
afforded. Instead, a good yield of 2-aryl analogue (4aa) was
achieved, which was characterized by NMR and MS methods
C
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a
Table 3. Reaction of 2-Aminobenzenethiols with Various Ketones Mediated by PhNO2
a
Reaction conditions: 1 (1.5 mmol), 2 (1 mmol), PhNO2 (1 mmol), 1,4-dioxane (2 mL), and iodine (10 mol %) in a reaction vessel at 110 °C for
b
4−8 h. The reaction was carried out in the same conditions but with 1 equiv of I2.
higher yield of 4aa was obtained (entry 16 vs 12). However,
other solvents such as PhCl, DMF, and DMA failed to facilitate
the reaction (entries 17−19). On the other hand, the reaction
in PhCl or in 1,4-dioxane mediated by DMSO gave 4aa at 48
and 15% yields, respectively, and surprisingly, 3aa was not
detected in these conditions (entries 20−21). The reaction
temperature was also examined. The reaction mediated by
PhNO2 did not proceed at 80 °C (entry 22). On the other
hand, lower yields of 3aa were afforded when the temperature
of the reaction in DMSO decreased (entries 23−24). Based on
these studies, the optimal reaction conditions for the
production of 3aa were established as listed in entry 13 and
the optimal reaction conditions for 4aa were set up as
described in entry 16.
With the optimized reaction conditions in hand, the
substrate scope and generality of the reaction mediated by
DMSO were explored (Table 2). Various substituted aromatic
methyl ketones containing both electron-donating group
(EDG) and electron-withdrawing group (EWG) were
examined. Acetophenones, bearing either an EDG, such as
methoxy and methyl group or an EWG, such as fluoro and
chloro group on the aromatic ring, underwent the reaction
smoothly to afford the corresponding 2-aroylbenzothiazoles in
moderate to good yields (3aa−3an). It was found that the
positions of both EDG and EWG on the aromatic ring had no
appreciable influence on the product yield, while the electronic
nature of the aryl moiety slightly affected the yield.
Acetophenones containing an EDG gave moderately higher
yield by compared with those containing an EWG (3ab vs 3ad,
3ae vs 3af, 3ai vs 3ah, and 3an). It is worth noting that the
hydroxyl and amino-containing acetophenones were also well
tolerable for the transformation (3ac and 3ak). In addition, 2-
acetonaphthone (2p) and several heterocyclic ketones (2q−
2t) were also investigated for this transformation, and all of
them were found to be smoothly converted to the
corresponding 2-aroylbenzothiazoles (3ap−3at) in 48−62%
yields. To further expand the substrate scope, two aliphatic
ketones such as pinacolone (2u) and acetone (2v) were also
investigated. Unfortunately, the desired 2-aroyl-substituted
products were not afforded. Instead, 63% yield of 2-(tert-
butyl)benzothiazole (4au) and 75% yield of 2,2-dimethyl-2,3-
dihydrobenzothiazole (5av) were given from pinacolone and
acetone, respectively. Furthermore, 2-amino-4-chlorobenzene-
thiol (1b) was also successfully reacted with acetophenones
(2) to give the corresponding 2-aroylbenzothiazoles in 53−
89% yields, which are better than those from 1a (3bh vs 3ah,
3bn vs 3an, 3bp vs 3ap, and 3br vs 3ar).
Having established an efficient synthesis of 2-aroylbenzo-
thiazoles (3) from 2-aminobenzenethiols (1) and acetophe-
nones (2) in DMSO catalyzed by I2, we then turned our
D
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attention to explore the substrate scope and generality of the
reaction mediated by PhNO2 (Table 3). Similar to the results
mentioned above, all of the investigated substrates were
tolerable to this transformation and gave good yields of the
corresponding 2-aryl-substituted benzothiazoles, regardless of
the electronic nature and the position of the substituted group
(4aa−4ao). It is worthy to be noted that 4ak, which contains
an amino group, can be further conjugated with a ligand as
antitumor agents or imaging probes.15 In addition, 2-
acetonaphthone (2p) was also successfully converted into
the corresponding product 4ap in a good yield, and
heterocyclic ketones (2q−2s) gave moderate yields of 4aq−
4as. When an aliphatic ketone such as pinacolone was
examined for the reaction mediated by PhNO2, the desired
product 4au was not observed. However, a moderate yield of
4au was achieved when increasing the dose of I2 to 1 equiv. In
other cases, the same product (5av) as that mediated by
DMSO was observed in a good yield when acetone was
examined for the reaction. Again, 4-chloro-substituted 2-
aminobenzenethiol (1b) was also tolerated to the reaction, and
73−85% yields of the expected products 4ba−4bo were
isolated.
(1 equiv) (eq 4). In contrast, a 2:1 molar ratio of 3aa:4aa was
detected when the reaction catalyzed by I2 was carried out in
DMSO (eq 5). This result indicates that the production of 5aa
from 1a and 2a (eq 3) in DMSO is reversible. Considering that
PhNO2 in the reaction was used as an oxidant and its reduced
form aniline was detected by gas chromatography−mass
spectrometry (GC−MS), we attempted to investigate 2w
which contains one nitro group as both a substrate and an
oxidant for this conversion in the absence of PhNO2.
Unfortunately, the expected product 4 was not successfully
afforded. Instead, compound 5aw was given in a moderate
yield (eq 6). Further conversion of 5aw into 4aw under the
standard conditions failed, mostly likely due to the strong
electron-withdrawing property of the nitro group.
On the basis of these preliminary experimental results and
previous literature reports,8b,d,16 a possible reaction mechanism
is proposed as follows using 2-aminobenzenethiol (1a) and
acetophenone (2a) as an example (Scheme 3). Initially,
acetophenone 2a was promoted by I2 to afford A in the
presence of DMSO, which was further converted into
phenylglyoxal B by Kornblun oxidation. Intermediate B
condenses with 2-aminobenzenethiol 1a to furnish an imine
C, and one molecule of water is removed. The intermediate C
undergoes spontaneous cyclization, followed by oxidation
catalyzed by iodine in the presence of DMSO. Elimination
of HI from intermediate E affords the final 2-aroylbenzothia-
zoles 3aa. When the reaction of 1a and 2a was performed in
the presence of nitrobenzene or 1,4-dioxane, condensation was
carried out prior to the oxidation of 2a to generate the
corresponding imine F, which is spontaneously cyclized to
afford an intermediate 5aa. Oxidation of the methyl group by
iodine generates intermediate G. In this process, the byproduct
HI could be oxidized by nitrobenzene to regenerate iodine.
Subsequently, intermediate G could be oxidized with PhNO2
to form its oxo derivative H, which has been detected
successfully by GC−MS after 1 h reaction of 1a and 2a under
the standard conditions. Aromatization of the intermediate H
with an elimination of formaldehyde produces the final 2-
phenyl benzothiazole 4aa.
In order to demonstrate the relationship between the
product yield and the dose of the oxidant, the reaction was
performed in 1,4-dioxane with different doses of DMSO or
PhNO2, and the result is presented in Figure 1. It can be seen
Figure 1. Relationship between the yield of 3aa and 4aa with the dose
of DMSO or PhNO2. The reaction of 1a (1.5 mmol), 2a (1 mmol),
and I2 (10%) in 1,4-dioxane with DMSO or PhNO2 at the indicated
dose in a reaction vessel was carried out at 110 °C for 2 h.
CONCLUSIONS
■
In conclusion, we have developed an I2-catalyzed domino
annulation of aromatic methyl ketones and 2-aminobenzene-
thiols under metal-free conditions. Under the optimal reaction
conditions, the versatile synthetic approach can not only
produce 2-aroyl benzothiazoles but also afford 2-aryl
benzothiazoles selectively by altering the oxidant/solvent.
Using DMSO as the oxidant/solvent, 2-aroyl benzothiazoles
were selectively achieved while the reaction mediated by
PhNO2 gave 2-aryl benzothiazoles only. The operational
simplicity, insensitivity to air and moisture, the reaction
selectivity, and generality of the present protocol render the
method attractive. Further application of this novel PhNO2/I2
co-catalytic system is currently undergoing in our lab.
that only 4aa at a low yield was obtained when DMSO at 1−2
equiv was applied. When the dose of DMSO was increased up
to 10 equiv, the yield of 4aa was improved, being accompanied
by the production of 3aa at a moderate yield. However, only
3aa was afforded in a good yield when the reaction was
performed by using DMSO as the sole solvent. In contrast, the
reaction in 1,4-dioxane with different doses of PhNO2 gave 4aa
only at good yields.
To elucidate the reaction mechanism, some controlled
experiments were undertaken (Scheme 2). First, it was found
that 8% yield of phenylglyoxal was achieved when 2a was
heated at 110 °C for 2 h in DMSO in the presence of I2 (10%)
(eq 1). In contrast, 2a was fully recovered when the reaction
was performed in 1,4-dioxane in the presence of PhNO2 (eq
2). In the absence of DMSO or PhNO2, the reaction of 1a and
2a gave 2,3-dihydrobenzothiazole (5aa), a key intermediate for
the production of 2-arylbenzothiazoles (eq 3). 5aa can be
further converted into the desired product 4aa in 1,4-dioxane
with an excellent yield in the presence of I2 (10%) and PhNO2
EXPERIMENTAL SECTION
General Methods. All the starting materials, reagents, and
■
solvents were purchased from commercial sources and used as
1
received. H and 13C NMR spectra were recorded at 400 and 101
MHz, respectively. High-resolution mass spectra (HRMS) of new
compounds were recorded on a Waters SYNAPT G2-Si mass
spectrometer with quadrupole time-of-flight tandem mass spectrom-
etry analysis. High performance liquid chromatography analyses were
E
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Scheme 2. Control Experiments
carried out on an Agilent 1260 Infinity II instrument. Melting points
were determined using an X-4 digital micro melting point apparatus.
All reactions were monitored by thin-layer chromatography (TLC)
using silica gel plates (silica gel 60 F254).
167.1, 153.9, 137.0, 135.0, 133.9, 131.3, 128.5, 127.65, 127.0, 125.8,
122.2; ESI-MS: m/z [M + 1]+, 240.
Benzo[d]thiazol-2-yl(2-methoxyphenyl)methanone (3ab).17 Pe-
troleum ether/ethyl acetate = 3:1; a white solid (186 mg, 69%); mp:
107−110 °C; 1H NMR (400 MHz, CDCl3): δ 8.14−8.17 (m, 1H),
7.98−8.02 (m, 1H), 7.77 (dd, J = 7.6, 1.8 Hz, 1H), 7.50−7.58 (m,
3H), 7.10 (t, J = 7.6 Hz, 1H), 7.06 (d, J = 8.4 Hz, 1H), 3.80 (s, 3H);
13C{1H} NMR (101 MHz, CDCl3): δ 188.1, 167.3, 158.8, 153.7,
137.2, 133.7, 131.2, 127.5, 126.8, 126.3, 125.7, 122.3, 120.4, 112.1,
56.0; ESI-MS: m/z [M + 1]+, 270.
General Procedure for the Synthesis of 3 (3aa as an
Example). The reaction in a reaction vessel was carried out with 1a
(1.5 mmol, 1.5 equiv), 2a (1 mmol, 1 equiv), and iodine (0.1 mmol,
0.1 equiv) in DMSO (2 mL) at 110 °C in an oil bath for 2 h. After
disappearance of the reactant (monitored by TLC), water (10 mL)
was added, and the mixture was extracted with EtOAc (15 mL × 3).
The combined organic layer was washed with 10% Na2S2O3 solution
(20 mL) and brine (20 mL) and then dried over anhydrous Na2SO4.
The solvent was removed under reduced pressure, and the residue
was purified by chromatography on silica gel to afford the desired 3aa
(184 mg, 77%).
Benzo[d]thiazol-2-yl(2-hydroxyphenyl)methanone (3ac).18 Pe-
troleum ether/ethyl acetate = 1:1; a yellow solid (179 mg, 70%);
1
mp: 77−79 °C; H NMR (400 MHz, CDCl3): δ 12.10 (s, 1H), 9.26
(d, J = 8.0 Hz, 1H), 8.25 (d, J = 8.4 Hz, 1H), 8.02 (d, J = 7.6 Hz, 1H),
7.54−7.62 (m, 3H), 7.02−7.08 (m, 2H); 13C{1H} NMR (101 MHz,
CDCl3): δ 187.65, 167.10, 164.17, 153.69, 137.53, 136.72, 134.07,
127.86, 127.13, 125.70, 122.11, 119.55, 118.43, 118.14; ESI-MS: m/z
[M + 1]+, 256.
General Procedure for the Synthesis of 4 (4aa as an
Example). The reaction in a reaction vessel was carried out with 1a
(1.5 mmol, 1.5 equiv), 2a (1 mmol, 1 equiv), PhNO2 (1 mmol, 1
equiv), and iodine (0.1 mmol, 0.1 equiv) in 1,4-dioxane (2 mL) at
110 °C in an oil bath for 4−8 h. After disappearance of the reactant
(monitored by TLC), water (10 mL) was added and the mixture was
extracted with EtOAc (15 mL × 3). The combined organic layer was
washed with 10% Na2S2O3 solution (20 mL) and brine (20 mL) and
then dried over anhydrous Na2SO4. The solvent was removed under
reduced pressure, and the residue was purified by chromatography on
silica gel to afford the desired 4aa (169 mg, 80%).
Benzo[d]thiazol-2-yl(2-chlorophenyl) methanone (3ad).17 Petro-
leum ether/ethyl acetate = 3:1; a white solid (183 mg, 67%); mp: 76−
78 °C; 1H NMR (400 MHz, CDCl3): δ 8.15−8.18 (m, 1H), 8.00−
8.04 (m, 1H), 7.77 (d, J = 8.0 Hz, 1H), 7.50−7.58 (m, 4H), 7.41−
7.45 (m, 1H); 13C{1H} NMR (101 MHz, CDCl3): δ 187.6, 165.9,
153.7, 137.4, 136.0, 132.6, 132.4, 130.8, 130.6, 128.0, 127.1, 126.5,
126.0, 122.4; ESI-MS: m/z [M + 1]+, 274.
Benzo[d]thiazol-2-yl(3-methoxyphenyl)methanone (3ae).17 Pe-
troleum ether/ethyl acetate = 3:1; a white solid (215 mg, 80%); mp:
Benzo[d]thiazol-2-yl(phenyl)methanone (3aa).8b Petroleum
ether/ethyl acetate = 3:1; a white solid (184 mg, 77%), mp: 98−99
°C; 1H NMR (400 MHz, CDCl3): δ 8.56 (d, J = 7.2 Hz, 2H), 8.25 (d,
J = 7.6 Hz, 1H), 8.02 (d, J = 7.6 Hz, 1H), 7.67 (t, J = 7.2 Hz, 1H),
7.63−7.52 (m, 4H); 13C{1H} NMR (101 MHz, CDCl3): δ 185.4,
1
88−89 °C; H NMR (400 MHz, CDCl3): δ 8.22−8.26 (m, 2H),
8.01−8.06 (m, 2H), 7.53−7.61 (m, 2H), 7.48 (t, J = 8.0 Hz, 1H),
7.22 (ddd, J = 8.0, 2.0, 0.8 Hz, 1H), 3.91 (s, 3H); 13C{1H} NMR
(101 MHz, CDCl3): δ 185.1, 167.1, 159.6, 153.9, 137.0, 136.1, 129.6,
F
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Scheme 3. Plausible Reaction Mechanism
127.7, 127.0, 125.8, 124.2, 122.2, 120.6, 115.3, 55.5; ESI-MS: m/z [M
+ 1]+, 270.
(m, 2H), 6.77 (d, J = 2.4 Hz, 2H), 3.89 (s, 6H); 13C{1H} NMR (101
MHz, CDCl3): δ 184.9, 167.0, 160.7, 153.8, 137.0, 136.5, 127.7,
126.9, 125.8, 122.3, 109.0, 106.7, 55.7; HRMS (ESI): calcd for
C16H14NO3S m/z [M + H]+, 300.0689; found, 300.0681.
Benzo[d]thiazol-2-yl(3-chlorophenyl)methanone (3af).17 Petro-
leum ether/ethyl acetate = 3:1; a white solid (177 mg, 65%); mp: 88−
90 °C; 1H NMR (400 MHz, CDCl3): δ 8.56 (s, 1H), 8.48 (d, J = 7.6
Hz, 1H), 8.26 (d, J = 7.6 Hz, 1H), 8.03 (d, J = 7.6 Hz, 1H), 7.55−
7.66 (m, 3H), 7.51 (t, J = 8.0 Hz, 1H); 13C{1H} NMR (101 MHz,
CDCl3): δ 184.0, 166.4, 153.8, 137.1, 136.4, 134.7, 133.8, 131.2,
129.8, 129.5, 127.9, 127.1, 125.9, 122.2; ESI-MS: m/z [M + 1]+, 274.
Benzo[d]thiazol-2-yl(4-fluorophenyl)methanone (3ah).17 Petro-
leum ether/ethyl acetate = 3:1; a red solid (177 mg, 69%); mp: 109−
Benzo[d]thiazol-2-yl(3,4-dimethylphenyl)methanone (3am).17
Petroleum ether/ethyl acetate = 4:1; colorless oil (155 mg, 58%);
1H NMR (400 MHz, CDCl3): δ 8.34 (dd, J = 7.9, 1.8 Hz, 1H), 8.22−
8.26 (m, 2H), 8.01 (d, J = 7.2 Hz, 1H), 7.51−7.61 (m, 2H), 7.31 (d, J
= 8.0 Hz, 1H), 2.39 (s, 3H), 2.37 (s, 3H); 13C{1H} NMR (101 MHz,
CDCl3): δ 185.3, 167.6, 153.9, 143.9, 137.0 (2C), 132.8, 132.1, 129.8,
129.3, 127.5, 126.8, 125.7, 122.2, 19.9 ppm; ESI-MS: m/z [M + 1]+,
268.
1
111 °C; H NMR (400 MHz, CDCl3): δ 8.67 (dd, J = 8.6, 5.5 Hz,
2H), 8.24 (d, J = 7.9 Hz, 1H), 8.02 (d, J = 7.8 Hz, 1H), 7.60 (t, J = 7.2
Hz, 1H), 7.55 (t, J = 7.2 Hz, 1H), 7.23 (d, J = 8.0 Hz, 2H); 13C{1H}
NMR (101 MHz, CDCl3): δ 183.6, 167.0, 166.4 (d, J = 255 Hz),
153.8, 137.0, 134.2 (d, J = 9.4 Hz), 131.3 (d, J = 3.0 Hz), 127.7,
127.0, 125.7, 122.2, 115.8 (d, J = 21.7 Hz); ESI-MS: m/z [M + 1]+,
258.
Benzo[d]thiazol-2-yl(3,5-difluorophenyl)methanone (3an). Pe-
troleum ether/ethyl acetate = 4:1; a white solid (143 mg, 52%);
mp: 89−92 °C; 1H NMR (400 MHz, CDCl3): δ 8.25 (d, J = 7.6 Hz,
1H), 8.19 (d, J = 6.0 Hz, 2H), 8.01 (d, J = 8.4 Hz, 1H), 7.61 (t, J = 7.2
Hz, 1H), 7.56 (t, J = 7.2 Hz, 1H), 7.09−7.14 (m, 1H); 13C{1H} NMR
(101 MHz, CDCl3): δ 182.5, 166.0, 162.7 (dd, J = 248, 11.9 Hz),
153.8, 137.4 (t, J = 8.6 Hz), 137.1, 128.1, 127.3, 126.0, 122.2, 114.3
(dd, J = 19.3, 7.5 Hz), 109.2 (t, J = 25.2 Hz); HRMS (ESI): calcd for
C14H8F2NOS m/z [M + H]+, 276.0289; found, 276.0294.
Benzo[d]thiazol-2-yl(p-tolyl)methanone (3ai).8b Petroleum
ether/ethyl acetate = 3:1; a white solid (190 mg, 75%); mp: 79−81
°C; 1H NMR (400 MHz, CDCl3): δ 8.47 (d, J = 8.0 Hz, 2H), 8.23 (d,
J = 8.0 Hz, 1H), 8.00 (d, J = 8.0 Hz, 1H), 7.51−7.59 (m, 2H), 7.35
(d, J = 8.0 Hz, 2H), 2.46 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3):
δ 184.9, 167.3, 153.9, 145.0, 137.0, 132.4, 131.4, 129.3, 127.5, 126.9,
125.7, 122.2, 21.9; ESI-MS: m/z [M + 1]+, 254.
Benzo[d]thiazol-2-yl(naphthalen-2-yl)methanone (3ap).8b Pe-
troleum ether/ethyl acetate = 3:1; a white solid (150 mg, 52%);
mp: 145−147 °C; 1H NMR (400 MHz, CDCl3): δ 9.33 (s, 1H), 8.43
(d, J = 7.6 Hz, 1H), 8.29 (d, J = 8.0 Hz, 1H), 8.07 (d, J = 8.0 Hz, 1H),
8.03 (d, J = 7.6 Hz, 1H), 7.97 (d, J = 8.8 Hz, 1H), 7.90 (d, J = 8.0 Hz,
1H), 7.53−7.66 (m, 4H); 13C{1H} NMR (101 MHz, CDCl3): δ
185.1, 167.4, 154.0, 137.1, 136.0, 134.4, 132.5, 132.2, 130.3, 129.1,
128.4, 127.8, 127.6, 127.0, 126.8, 125.8, 125.8, 122.2; ESI-MS: m/z
[M + 1]+, 290.
(4-Aminophenyl)(benzo[d]thiazol-2-yl)methanone (3ak).19 Pe-
troleum ether/ethyl acetate = 2:1; a yellow solid (183 mg, 72%); mp:
1
165−167 °C; H NMR (400 MHz, CDCl3): δ 8.53 (d, J = 8.4 Hz,
2H), 8.21 (d, J = 8.0 Hz, 1H), 7.99 (d, J = 7.9 Hz, 1H), 7.56 (t, J = 7.8
Hz, 1H), 7.51 (t, J = 7.8 Hz, 1H), 6.73 (d, J = 8.4 Hz, 2H), 4.32 (s,
2H); 13C{1H} NMR (101 MHz, CDCl3): δ 182.6, 168.6, 153.9,
152.2, 136.8, 134.2, 127.1, 126.6, 125.4, 125.0, 122.1, 113.8; ESI-MS:
m/z [M + 1]+, 255.
Benzo[d]thiazol-2-yl(thiophen-2-yl)methanone (3aq).8b Petrole-
um ether/ethyl acetate = 2:1; a yellow solid (130 mg, 53%); mp: 95−
97 °C; 1H NMR (400 MHz, CDCl3): δ 8.77 (d, J = 3.2 Hz, 1H), 8.24
(d, J = 8.0 Hz, 1H), 8.01 (d, J = 7.8 Hz, 1H), 7.84 (d, J = 4.8 Hz, 1H),
7.59 (t, J = 7.8 Hz, 1H), 7.54 (t, J = 8.0 Hz, 1H), 7.27 (d, J = 4.8 Hz,
1H); 13C{1H} NMR (101 MHz, CDCl3): δ 177.0, 166.6, 153.7,
Benzo[d]thiazol-2-yl(3,5-dimethoxyphenyl)methanone (3al). Pe-
troleum ether/ethyl acetate = 4:1; a grey solid (182 mg, 61%); mp:
1
105−108 °C; H NMR (400 MHz, CDCl3): δ 8.24 (d, J = 7.6 Hz,
1H), 8.02 (d, J = 7.6 Hz, 1H), 7.74 (d, J = 2.4 Hz, 2H), 7.53−7.610
G
https://dx.doi.org/10.1021/acs.joc.0c02095
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
139.7, 137.4, 137.0, 136.8, 128.5, 127.6, 127.0, 125.6, 122.3; ESI-MS:
m/z [M + 1]+, 246.
168.1, 154.5, 143.9, 139.4, 139.2, 135.6, 135.2, 133.2, 128.3, 128.3,
126.9, 125.2 (2C), 123.0, 122.8; HRMS (ESI): calcd for
C14H7ClF2NOS m/z [M + H]+, 309.9899; found, 309.9893.
2-Phenylbenzo[d]thiazole (4aa).8d Petroleum ether/ethyl acetate
Benzo[b]thiophen-2-yl(benzo[d]thiazol-2-yl)methanone (3ar).
Petroleum ether/ethyl acetate = 3:1; a yellow solid (174 mg, 59%);
mp: 147−150 °C; 1H NMR (400 MHz, CDCl3): δ 9.17 (s, 1H), 8.31
(d, J = 8.0 Hz, 1H), 8.03 (d, J = 8.0 Hz, 2H), 7.93 (d, J = 8.0 Hz, 1H),
7.63 (dt, J = 1.2, 7.6 Hz, 1H), 7.57 (dt, J = 1.2, 7.6 Hz, 1H), 7.52 (dt,
J = 1.2, 7.6 Hz, 1H), 7.45 (dt, J = 1.2, 7.6 Hz, 1H); 13C{1H} NMR
(101 MHz, CDCl3): δ 178.4, 166.3, 153.8, 143.8, 139.6, 139.3, 137.0,
135.4, 128.1, 127.7, 127.1, 126.9, 125.7, 125.1, 122.8, 122.3; HRMS
(ESI): calcd for C16H10NOS2 m/z [M + H]+, 296.0198; found,
296.0191.
1
= 3:1; a yellow solid (169 mg, 80%); mp: 100−102 °C; H NMR
(400 MHz, CDCl3): δ 8.06−8.12 (m, 3H), 7.91 (d, J = 8.0 Hz, 1H),
7.48−7.52 (m, 4H), 7.39 (td, J = 8.0, 0.8 Hz, 1H); 13C{1H} NMR
(101 MHz, CDCl3): δ 168.1, 154.2, 135.1, 133.6, 131.0, 129.1, 127.6,
126.4, 125.2, 123.3, 121.7; ESI-MS: m/z [M + 1]+, 212.
(2-Methoxyphenyl)benzo[d]thiazole (4ab).8d Petroleum ether/
1
ethyl acetate = 3:1; a red solid (193 mg, 80%); mp: 99−102 °C; H
NMR (400 MHz, CDCl3): δ 8.53 (dd, J = 7.9, 1.8 Hz, 1H), 8.09 (d, J
= 8.0 Hz, 1H), 7.93 (d, J = 8.0 Hz, 1H), 7.44−7.51 (m, 2H), 7.37 (td,
J = 8.0, 0.8 Hz, 1H), 7.14 (td, J = 8.1, 1.1 Hz, 1H), 7.07 (d, J = 8.0 Hz,
1H), 4.06 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3): δ 163.1,
157.2, 152.1, 136.1, 131.8, 129.6, 125.9, 124.6, 122.8, 122.3, 121.2,
121.2, 111.7, 55.7; ESI-MS: m/z [M + 1]+, 242.
Benzo[d]thiazol-2-yl(benzofuran-2-yl)methanone (3as).8b Petro-
leum ether/ethyl acetate = 4:1; a white solid (134 mg, 48%); mp:
179−180 °C; 1H NMR (400 MHz, CDCl3): δ 8.80 (s, 1H), 8.29 (d, J
= 8.0 Hz, 1H), 8.05 (d, J = 7.6 Hz, 1H), 7.85 (d, J = 7.6 Hz, 1H), 7.69
(d, J = 8.0 Hz, 1H), 7.64 (td, J = 7.2, 1.2 Hz, 1H), 7.53−7.60 (m,
2H), 7.37 (td, J = 7.6, 1.0 Hz, 1H); 13C{1H} NMR (101 MHz,
CDCl3): δ 174.0, 165.9, 156.4, 153.8, 149.8, 137.0, 129.3, 127.8,
127.4, 127.2, 125.6, 124.2, 122.3, 121.1, 112.7; ESI-MS: m/z [M +
1]+, 280.
(2-Chlorophenyl)benzo[d]thiazole (4ad).8d Petroleum ether/ethyl
acetate = 4:1; a yellow solid (189 mg, 77%); mp: 64−66 °C; 1H NMR
(400 MHz, CDCl3): δ 8.20−8.22 (m, 1H), 8.14 (d, J = 8.2 Hz, 1H),
7.95 (d, J = 8.0 Hz, 1H), 7.51−7.55 (m, 2H), 7.40−7.45 (m, 3H);
13C{1H} NMR (101 MHz, CDCl3): δ 164.2, 152.5, 136.1, 132.7,
132.3, 131.8, 131.2, 130.8, 127.2, 126.3, 125.5, 123.5, 121.4; ESI-MS:
m/z [M + 1]+, 246.
Benzo[d]thiazol-2-yl(1H-indol-3-yl)methanone (3at).8b Petrole-
um ether/ethyl acetate = 4:1; a yellow solid (172 mg, 62%); mp:
252−254 °C; 1H NMR (400 MHz, DMSO-d6): δ 12.38 (s, 1H), 9.26
(s, 1H), 8.19−8.38 (m, 3H), 7.56−7.69 (m, 3H), 7.28−7.33 (m, 2H);
13C{1H} NMR (101 MHz, DMSO-d6): δ 178.3, 170.0, 153.9, 138.7,
136.9, 136.3, 127.5, 127.3, 126.9, 125.3, 124.0, 123.1, 123.0, 122.0,
113.1, 113.1; ESI-MS: m/z [M + 1]+, 279.
2-(3-Methoxyphenyl)benzo[d]thiazole (4ae).20 Petroleum ether/
ethyl acetate = 3:1; a white solid (161 mg, 67%); mp: 75−77 °C; 1H
NMR (400 MHz, CDCl3): δ 8.07 (d, J = 8.1, 1H), 7.88 (d, J = 7.9 Hz,
1H), 7.66−7.68 (m, 1H), 7.63 (td, J = 7.6, 1.2 Hz, 1H), 7.48 (td, J =
7.2, 1.2 Hz, 1H), 7.34−7.39 (m, 2H), 7.02 (dd, J = 8.0, 2.4 Hz, 1H),
3.89 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3): δ 168.0, 160.1,
154.1, 135.1, 130.1, 126.3, 125.3, 123.3, 121.6, 120.3, 117.4, 112.0,
55.5; ESI-MS: m/z [M + 1]+, 242.
(5-Chlorobenzo[d]thiazol-2-yl)(phenyl)methanone (3ba).8b Pe-
troleum ether/ethyl acetate = 3:1; a red solid (145 mg, 53%); mp:
1
116−118 °C; H NMR (400 MHz, CDCl3): δ 8.55 (d, J = 8.8 Hz,
2H), 8.24 (d, J = 1.9 Hz, 1H), 7.94 (d, J = 8.6 Hz, 1H), 7.69 (t, J = 7.6
Hz, 1H), 7.57 (t, J = 7.8 Hz, 2H), 7.53 (dd, J = 8.8, 1.9 Hz, 1H);
13C{1H} NMR (101 MHz, CDCl3): δ 184.9, 168.9, 154.6, 135.2,
2-(3-Chlorophenyl)benzo[d]thiazole (4af).21 Petroleum ether/
ethyl acetate = 3:1; a white solid (154 mg, 63%); mp: 92−93 °C;
1H NMR (400 MHz, CDCl3): δ 8.10 (t, J = 1.6 Hz, 1H), 8.07 (d, J =
8.0 Hz, 1H), 7.92 (dt, J = 7.6, 1.6 Hz, 1H), 7.88 (d, J = 8.0 Hz, 1H),
7.49 (td, J = 7.2, 1.2 Hz, 1H), 7.36−7.45 (m, 3H); 13C{1H} NMR
(101 MHz, CDCl3): δ 166.3, 154.0, 135.3, 135.2, 135.1, 130.9, 130.3,
127.4, 126.6, 125.7, 125.6, 123.5, 121.7; ESI-MS: m/z [M + 1]+, 246.
2-(4-Chlorophenyl)benzo[d]thiazole (4ag).8d Petroleum ether/
134.7, 134.1, 133.0, 131.3, 128.6, 128.2, 125.3, 123.0; ESI-MS: m/z
[M + 1]+, 274.
(5-Chlorobenzo[d]thiazol-2-yl)(4-fluorophenyl)methanone
(3bh).14 Petroleum ether/ethyl acetate = 4:1; a red solid (259 mg,
89%); mp: 139−142 °C; 1H NMR (400 MHz, CDCl3): δ 8.67 (dd, J
= 5.4, 8.4 Hz, 2H), 8.24 (d, J = 1.6 Hz, 1H), 7.94 (d, J = 8.4 Hz, 1H),
7.53 (dd, J = 8.4, 1.6 Hz, 1H), 7.24 (t, J = 8.4 Hz, 2H); 13C{1H}
NMR (101 MHz, CDCl3): δ 183.1, 168.8, 166.5 (d, J = 256 Hz),
154.6, 135.2, 134.2 (d, J = 9.4 Hz), 133.1, 131.0 (d, J = 3.0 Hz),
128.3, 125.2, 123.0, 115.8 (d, J = 21.7 Hz); ESI-MS: m/z [M + 1]+,
292.
1
ethyl acetate = 3:1; a red solid (172 mg, 70%); mp: 98−101 °C; H
NMR (400 MHz, CDCl3): δ 8.06 (d, J = 8.0 Hz, 1H), 8.02 (d, J = 8.0
Hz, 2H), 7.90 (d, J = 8.0 Hz, 1H), 7.49 (t, J = 9.2 Hz, 1H), 7.46 (d, J
= 8.0 Hz, 2H), 7.39 (t, J = 7.6 Hz, 1H); 13C{1H} NMR (101 MHz,
CDCl3): δ 166.6, 154.1, 137.0, 135.1, 132.1, 129.3, 128.7, 126.5,
125.4, 123.3, 121.7; ESI-MS: m/z [M + 1]+, 246.
(5-Chlorobenzo[d]thiazol-2-yl)(3,5-difluorophenyl)methanone
(3bn). Petroleum ether/ethyl acetate = 3:1; a yellow solid (232 mg,
75%); mp: 164−165 °C; 1H NMR (400 MHz, CDCl3): δ 8.27 (d, J =
2.0 Hz, 1H), 8.15−8.20 (m, 2H), 7.95 (d, J = 8.4 Hz, 1H), 7.55 (dd, J
= 8.4, 2.0 Hz, 1H), 7.13 (tt, J = 8.4, 2.4 Hz, 1H); 13C{1H} NMR (101
MHz, CDCl3): δ 182.2, 167.7, 162.8 (dd, J = 249, 11.7 Hz), 154.5,
137.1 (t, J = 8.8 Hz), 135.3, 133.4, 128.7, 125.5, 123.0, 114.3 (dd, J =
19.3, 7.5 Hz), 109.4 (t, J = 25.2 Hz); HRMS (ESI): calcd for
C14H7ClF2NOS m/z [M + H]+, 309.9899; found, 309.9912.
(5-Chlorobenzo[d]thiazol-2-yl)(naphthalen-2-yl)methanone
(3bp). Petroleum ether/ethyl acetate = 4:1; a yellow solid (262 mg,
2-(p-Tolyl)benzo[d]thiazole (4ah).8d Petroleum ether/ethyl ac-
1
etate = 3:1; a white solid (187 mg, 83%); mp: 72−74 °C; H NMR
(400 MHz, CDCl3): δ 8.05 (d, J = 8.4 Hz, 1H), 7.98 (d, J = 8.0 Hz,
2H), 7.88 (d, J = 7.9 Hz, 1H), 7.47 (td, J = 8.3, 1.2 Hz, 1H), 7.36 (td,
J = 8.0, 1.2 Hz, 1H), 7.28 (d, J = 8.0 Hz, 2H), 2.41 (s, 3H); 13C{1H}
NMR (101 MHz, CDCl3): δ 168.3, 154.2, 141.5, 135.0, 131.0, 129.8,
127.5, 126.3, 125.0, 123.1, 121.6, 21.6; ESI-MS: m/z [M + 1]+, 226.
4-(Benzo[d]thiazol-2-yl)aniline (4ak).22 Petroleum ether/ethyl
1
acetate = 2:1; a white solid (174 mg, 77%); mp: 120−122 °C; H
NMR (400 MHz, CDCl3): δ 7.99 (d, J = 8.0 Hz, 1H), 7.90 (d, J = 8.4
Hz, 2H), 7.85 (d, J = 8.0 Hz, 1H), 7.44 (t, J = 8.0 Hz, 1H), 7.32 (d, J
= 8.0 Hz, 1H), 6.73 (d, J = 8.4 Hz, 1H), 4.00 (br s, 2H). 13C{1H}
NMR (101 MHz, CDCl3): δ 168.5, 154.3, 149.2, 134.6, 129.2, 126.1,
124.5, 124.0, 122.5, 121.4, 114.8; ESI-MS: m/z [M + 1]+, 227.
2-(3,5-Dimethoxyphenyl)benzo[d]thiazole (4al).23 Petroleum
1
81%); mp: 150−153 °C; H NMR (400 MHz, CDCl3): δ 9.33 (s,
1H), 8.41 (dd, J = 8.7, 1.7 Hz, 1H), 8.29 (d, J = 2.0 Hz, 1H), 8.07 (d,
J = 8.0 Hz, 1H), 7.96 (t, J = 8.4 Hz, 2H), 7.91 (d, J = 8.4 Hz, 1H),
7.65 (t, J = 7.8 Hz, 1H), 7.59 (t, J = 7.6 Hz, 1H), 7.53 (dd, J = 8.6, 2.0
Hz, 1H); 13C{1H} NMR (101 MHz, CDCl3): δ 184.6, 169.2, 154.7,
136.1, 135.2, 134.5, 133.0, 132.4, 131.9, 130.3, 129.2, 128.4, 128.2,
127.8, 126.9, 125.7, 125.3, 123.0; HRMS (ESI): calcd for
C18H11ClNOS m/z [M + H]+, 324.0244; found, 324.0231.
1
ether/ethyl acetate = 2:1; colorless oil (190 mg, 70%); H NMR
(400 MHz, CDCl3): δ 8.074 (d, J = 8.0 Hz, 1H), 7.88 (d, J = 8.0 Hz,
1H), 7.49 (td, J = 7.6, 1.3 Hz, 1H), 7.38 (td, J = 7.6, 0.8 Hz, 1H), 7.25
(d, J = 2.4 Hz, 2H), 6.59 (t, J = 2.3 Hz, 1H), 3.88 (s, 6H); 13C{1H}
NMR (101 MHz, CDCl3): δ 168.0, 161.1, 154.0, 135.4, 135.1, 126.3,
125.3, 123.3, 121.6, 105.5, 103.4, 55.6; ESI-MS: m/z [M + 1]+, 272.
2-(3,4-Dimethylphenyl)benzo[d]thiazole (4am).24 Petroleum
ether/ethyl acetate = 4:1; a white solid (172 mg, 72%); mp: 96−98
°C; 1H NMR (400 MHz, CDCl3): δ 8.05 (d, J = 8.0 Hz, 1H), 7.88 (s,
Benzo[b]thiophen-2-yl(5-chlorobenzo[d]thiazol-2-yl)methanone
(3br). Petroleum ether/ethyl acetate = 3:1; a yellow solid (280 mg,
1
85%); mp: 168−170 °C; H NMR (400 MHz, CDCl3): δ 9.12 (s,
1H), 8.28 (d, J = 2.0 Hz, 1H), 8.01 (d, J = 8.0 Hz, 1H), 7.92 (d, J =
8.8 Hz, 1H), 7.91 (d, J = 8.0 Hz, 1H), 7.49−7.53 (m, 2H), 7.44 (td, J
= 8.1 1.2 Hz, 1H); 13C{1H} NMR (101 MHz, CDCl3): δ 178.0,
H
https://dx.doi.org/10.1021/acs.joc.0c02095
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
1H), 7.86 (d, J = 7.6 Hz, 1H), 7.78 (d, J = 7.6 Hz, 1H), 7.46 (t, J = 7.6
Hz, 1H), 7.34 (t, J = 7.2 Hz, 1H), 7.23 (d, J = 8.4 Hz, 1H), 2.34 (s,
3H), 2.31 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3): δ 168.5,
154.2, 140.2, 137.4, 135.0, 131.3, 130.3, 128.5, 126.2, 125.2, 124.9,
123.0, 121.6, 19.9, 19.7; ESI-MS: m/z [M + 1]+, 240.
7.2 Hz, 1H), 7.36 (dd, J = 8.4, 2.0 Hz, 1H), 7.19 (t, J = 8.4 Hz, 2H);
13C{1H} NMR (101 MHz, CDCl3): δ 168.6, 164.7 (d, J = 251 Hz),
155.0, 133.3, 132.4, 129.6 (d, J = 8.6 Hz), 129.6, 125.7, 123.0, 122.3,
116.3 (d, J = 22.0 Hz); ESI-MS: m/z [M + 1]+, 264.
5-Chloro-2-(4-methoxyphenyl)benzo[d]thiazole (4bj).30 Petrole-
um ether/ethyl acetate = 2:1; a yellow solid (206 mg, 75%); mp:
2-(3,5-Difluorophenyl)benzo[d]thiazole (4an).25 Petroleum
ether/ethyl acetate = 3:1; a white solid (185 mg, 75%); mp: 104−
1
142−145 °C; H NMR (400 MHz, CDCl3): δ 8.00 (d, J = 8.4 Hz,
1
106 °C; H NMR (400 MHz, CDCl3): δ 8.09 (d, J = 8.0 Hz, 1H),
2H), 7.99 (s, 1H), 7.76 (d, J = 8.4 Hz, 1H), 7.31 (dd, J = 8.4, 1.6 Hz,
1H), 6.99 (t, J = 8.8 Hz, 2H), 3.88 (s, 3H); 13C{1H} NMR (101
MHz, CDCl3): δ 169.7, 162.2, 155.1, 133.1, 132.2, 129.2, 126.1,
125.2, 122.6, 122.2, 114.4, 55.5; ESI-MS: m/z [M + 1]+, 276.
5-Chloro-2-(3,5-difluorophenyl)benzo[d]thiazole (4bn). Petrole-
um ether/ethyl acetate = 2:1; a white solid (225 mg, 80%); mp: 155−
7.92 (d, J = 8.0 Hz, 1H), 7.63 (dd, J = 7.6, 2.4 Hz, 2H), 7.53 (td, J =
7.6, 1.3 Hz, 1H), 7.43 (td, J = 7.8, 1.2 Hz, 1H), 6.93 (tt, J = 7.6, 2.4
Hz, 1H); 13C{1H} NMR (101 MHz, CDCl3): δ 165.1 (t, J = 3.6 Hz),
163.3 (dd, J = 248, 12.6 Hz), 153.8, 136.6 (t, J = 9.8 Hz), 135.1,
126.7, 125.90, 123.7, 121.8, 110.5 (dd, J = 19.3, 7.8 Hz), 106.1 (t, J =
25.2 Hz); ESI-MS: m/z [M + 1]+, 248.
1
157 °C; H NMR (400 MHz, CDCl3): δ 8.05 (d, J = 1.6 Hz, 1H),
2-(2,4-Dimethylphenyl)benzo[d]thiazole (4ao).26 Petroleum
ether/ethyl acetate = 4:1; a pink solid (170 mg, 71%); mp: 31−33
°C; 1H NMR (400 MHz, CDCl3): δ 8.08 (d, J = 8.3 Hz, 1H), 7.90 (d,
J = 8.0 Hz, 1H), 7.67 (d, J = 7.9 Hz, 1H), 7.49 (t, J = 7.2 Hz, 1H),
7.38 (t, J = 7.2 Hz, 1H), 7.15 (s, 1H), 7.11 (d, J = 7.6 Hz, 1H), 2.64
(s, 3H), 2.38 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3): δ 168.2,
153.9, 140.2, 137.1, 135.5, 132.4, 130.6, 130.3, 126.9, 126.1, 124.9,
123.3, 121.3, 21.4, 21.3; ESI-MS: m/z [M + 1]+, 240.
7.81 (d, J = 8.4 Hz, 1H), 7.59 (d, J = 6.0 Hz, 2H), 7.39 (dd, J = 8.6,
2.0 Hz, 1H), 6.95 (tt, J = 7.6, 2.3 Hz, 1H); 13C{1H} NMR (101 MHz,
CDCl3): δ 166.9 (t, J = 3.5 Hz), 163.2 (dd, J = 249, 12.5 Hz), 154.6,
136.1 (t, J = 9.9 Hz), 133.3, 132.8, 126.4, 123.4, 122.4, 110.5 (dd, J =
19.4, 7.9 Hz), 106.4 (t, J = 25.3 Hz); HRMS (ESI): calcd for
C13H7ClF2NS m/z [M + H]+, 281.9950; found, 281.9932.
5-Chloro-2-(2,4-dimethylphenyl)benzo[d]thiazole (4bo). Petrole-
2-(Naphthalen-2-yl)benzo[d]thiazole (4ap).20 Petroleum ether/
ethyl acetate = 2:1; a yellow solid (193 mg, 74%); mp: 110−112 °C;
1H NMR (400 MHz, CDCl3): δ 8.57 (d, J = 1.2 Hz, 1H), 8.22 (dd, J
= 8.6, 1.8 Hz, 1H), 8.12 (d, J = 8.0 Hz, 1H), 7.93−7.99 (m, 3H),
7.87−7.90 (m, 1H), 7.49−7.58 (m, 3H), 7.41 (td, J = 8.0, 1.2 Hz,
1H); 13C{1H} NMR (101 MHz, CDCl3): δ 168.1, 154.2, 135.1,
134.6, 133.2, 131.0, 128.9 (2C), 127.9, 127.6, 127.5, 126.9, 126.4,
125.3, 124.5, 123.2, 121.7; ESI-MS: m/z [M + 1]+, 262.
um ether/ethyl acetate = 3:1; a yellow solid (199 mg, 73%); mp:
1
104−106 °C; H NMR (400 MHz, CDCl3): δ 8.06 (d, J = 1.9 Hz,
1H), 7.81 (d, J = 8.8 Hz, 1H), 7.66 (d, J = 8.4 Hz, 1H), 7.36 (dd, J =
8.4, 1.6 Hz, 1H), 7.16 (s, 1H), 7.12 (d, J = 7.6 Hz, 1H), 2.64 (s, 3H),
2.39 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3): δ 170.1, 154.7,
140.6, 137.2, 133.7, 132.5, 132.0, 130.6, 129.9, 127.0, 125.4, 123.0,
122.0, 21.5, 21.3; HRMS (ESI): calcd for C15H13ClNS m/z [M + H]+,
274.0452; found, 274.0463.
2-Methyl-2-phenyl-2,3-dihydrobenzo[d]thiazole (5aa).31 Petro-
2-(Thiophen-2-yl)benzo[d]thiazole (4aq).8d Petroleum ether/
ethyl acetate = 2:1; a yellow solid (130 mg, 60%); mp: 99−101
°C; 1H NMR (400 MHz, CDCl3): δ 8.03 (d, J = 8.4 Hz, 1H), 7.85 (d,
J = 8.0 Hz, 1H), 7.66 (d, J = 3.6 Hz, 1H), 7.50 (d, J = 5.2 Hz, 1H),
7.46 (t, J = 7.2 Hz, 1H), 7.37 (t, J = 8.0 Hz, 1H), 7.14 (t, J = 4.2 Hz,
1H). 13C{1H} NMR (101 MHz, CDCl3): δ 161.4, 153.7, 137.3, 134.7,
129.3, 128.6, 128.1, 126.5, 125.3, 123.0, 121.5; ESI-MS: m/z [M +
1]+, 218.
1
leum ether/ethyl acetate = 3:1; colorless liquid (104 mg, 46%); H
NMR (400 MHz, CDCl3): δ 7.83 (d, J = 7.6 Hz, 2H), 7.52 (t, J = 7.6
Hz, 2H), 7.45 (t, J = 7.6 Hz, 1H), 7.21 (dd, J = 7.6, 0.8 Hz, 1H), 7.15
(td, J = 7.6, 1.2 Hz, 1H), 6.96 (td, J = 7.6, 1.2 Hz, 1H), 6.89 (d, J =
7.6 Hz, 1H), 4.44 (br s, 1H), 2.20 (s, 3H); 13C{1H} NMR (101 MHz,
CDCl3): δ 146.1, 145.8, 128.6, 128.0, 127.5, 125.8, 125.6, 122.1,
121.2, 111.2, 78.5, 31.7; ESI-MS: m/z [M + 1]+, 228.
2-(Benzo[b]thiophen-2-yl)benzo[d]thiazole (4ar).27 Petroleum
ether/ethyl acetate = 4:1; a yellow solid (155 mg, 58%); mp: 185−
2,2-Dimethyl-2,3-dihydrobenzo[d]thiazole (5av).32 Petroleum
1
ether/ethyl acetate = 3:1; colorless liquid (124 mg, 75%); H NMR
1
188 °C; H NMR (400 MHz, CDCl3): δ 8.07 (d, J = 8.0 Hz, 1H),
(400 MHz, CDCl3): δ 7.05 (dd, J = 7.6, 0.8 Hz, 1H), 6.90 (td, J = 7.6,
1.2 Hz, 1H), 6.75 (td, J = 7.6, 0.8 Hz, 1H), 6.65 (dd, J = 7.6, 0.8 Hz,
1H), 3.91 (br s, 1H), 1.71 (s, 6H); 13C{1H} NMR (101 MHz,
CDCl3): δ 145.8, 128.5, 125.1, 122.1, 121.0, 111.5, 74.7, 31.7; ESI-
MS: m/z [M + 1]+, 166.
2-Methyl-2-(4-nitrophenyl)-2,3-dihydrobenzo[d]thiazole
(5aw).31 Petroleum ether/ethyl acetate = 3:1; colorless liquid (141
mg, 52%); 1H NMR (400 MHz, CDCl3): δ 8.17 (d, J = 8.0 Hz, 2H),
7.81 (d, J = 8.0 Hz, 2H), 6.97−7.04 (m, 2H), 6.81−6.85 (m, 2H),
4.33 (br s, 1H), 2.11 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3): δ
153.8, 147.1, 145.1, 127.9, 126.5, 125.7, 123.6, 122.1, 121.9, 112.2,
77.4, 30.8. ESI-MS: m/z [M + 1]+, 273.
7.81−7.86 (m, 4H), 7.49 (td, J = 7.8, 1.2 Hz, 1H), 7.36−7.42 (m,
3H); 13C{1H} NMR (101 MHz, CDCl3): δ 161.5, 153.7, 140.8,
139.6, 137.2, 135.0, 126.6, 126.2, 125.6, 125.3, 125.0, 124.6, 123.4,
122.6, 121.6; ESI-MS: m/z [M + 1]+, 268.
2-(Benzofuran-2-yl)benzo[d]thiazole (4as).28 Petroleum ether/
ethyl acetate = 4:1; a yellow solid (138 mg, 55%); mp: 189−191 °C;
1H NMR (400 MHz, CDCl3): δ 8.13 (d, J = 8.0 Hz, 1H), 7.94 (d, J =
8.0 Hz, 1H), 7.69 (d, J = 8.0 Hz, 1H), 7.63 (dd, J = 8.4, 0.9 Hz, 1H),
7.54 (d, J = 0.8 Hz, 1H), 7.53 (td, J = 7.6, 1.2 Hz, 1H), 7.39−7.45 (m,
2H), 7.31 (td, J = 7.6, 0.8 Hz, 1H); 13C{1H} NMR (101 MHz,
CDCl3): δ 157.6, 155.5, 153.9, 149.8, 134.7, 128.2, 126.7, 126.5,
125.7, 123.8, 123.5, 122.1, 121.7, 111.9, 107.6; ESI-MS: m/z [M +
1]+, 252.
(tert-Butyl)benzo[d]thiazole (4au).21 Petroleum ether/ethyl ac-
ASSOCIATED CONTENT
■
1
etate = 3:1; colorless liquid (120 mg, 63%); H NMR (400 MHz,
sı
* Supporting Information
CDCl3): δ 7.99 (d, J = 8.4 Hz, 1H), 7.83 (d, J = 8.0 Hz, 1H), 7.43 (t, J
= 8.0 Hz, 1H), 7.31 (t, J = 8.0 Hz, 1H), 1.52 (s, 9H); 13C{1H} NMR
(101 MHz, CDCl3): δ 181.8, 153.3, 135.0, 125.7, 124.5, 122.7, 121.5,
38.3, 30.8; ESI-MS: m/z [M + 1]+, 192.
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c02095.
1H NMR and 13C NMR spectra (PDF)
5-Chloro-2-phenylbenzo[d]thiazole (4ba).8d Petroleum ether/
ethyl acetate = 2:1; a white solid (191 mg, 78%); mp: 140−142
°C; 1H NMR (400 MHz, CDCl3): δ 8.03−8.08 (m, 3H), 7.79 (d, J =
8.4 Hz, 1H), 7.47−7.51 (m, 3H), 7.35 (dd, J = 8.4, 2.0 Hz, 1H);
13C{1H} NMR (101 MHz, CDCl3): δ 169.9, 155.0, 133.3, 133.3,
132.3, 131.4, 129.1, 127.6, 125.7, 123.1, 122.3; ESI-MS: m/z [M +
1]+, 246.
AUTHOR INFORMATION
■
Corresponding Author
Yongmin Ma − Institute of Advanced Studies and School of
Pharmaceutical and Chemical Engineering, Taizhou
University, Taizhou 318000, P R China; orcid.org/0000-
0002-9521-767X; Email: yongmin.ma@tzc.edu.cn
5-Chloro-2-(4-fluorophenyl)benzo[d]thiazole (4bh).29 Petroleum
ether/ethyl acetate = 2:1; a red solid (223 mg, 85%); mp: 139−142
°C; 1H NMR (400 MHz, CDCl3): δ 8.03−8.09 (m, 3H), 7.81 (t, J =
I
https://dx.doi.org/10.1021/acs.joc.0c02095
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
biosynthesis that occurs in the pupal stage of the Japanese firefly,
Luciola lateralis. Bioorg. Chem. 2018, 80, 223−229. (c) Wang, Y.-Q.;
Weng, Z.-M.; Dou, T.-Y.; Hou, J.; Wang, D.-D.; Ding, L.-L.; Zou, L.-
W.; Yu, Y.; Chen, J.; Tang, H.; Ge, G.-B. Nevadensin is a naturally
occurring selective inhibitor of human carboxylesterase 1. Int. J. Biol.
Macromol. 2018, 120, 1944−1954.
Authors
Renchao Ma − Institute of Advanced Studies and School of
Pharmaceutical and Chemical Engineering, Taizhou
University, Taizhou 318000, P R China
Yuxin Ding − Institute of Advanced Studies and School of
Pharmaceutical and Chemical Engineering, Taizhou
University, Taizhou 318000, P R China
Rener Chen − Institute of Advanced Studies and School of
Pharmaceutical and Chemical Engineering, Taizhou
University, Taizhou 318000, P R China
Zhiming Wang − Institute of Advanced Studies and School of
Pharmaceutical and Chemical Engineering, Taizhou
University, Taizhou 318000, P R China; orcid.org/
0000-0002-6583-3826
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sulfinate: a sulfinic acid transfer reagent under oxidation-free
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Meggers, E. Asymmetric photocatalysis with bis-cyclometalated
rhodium complexes. Acc. Chem. Res. 2019, 52, 833−847. (c) Mo-
hamed, K. S.; Fadda, A. A. Synthesis, characterization and cytotoxicity
evaluation of some novel pyrazole and pyrrole derivatives containing
benzothiazole moiety. Heterocycles 2015, 91, 1937−1954. (d) Taha,
M.; Ismail, N. H.; Imran, S.; Selvaraj, M.; Rahim, F. Synthesis of novel
inhibitors of β-glucuronidase based on the benzothiazole skeleton and
their molecular docking studies. RSC Adv. 2016, 6, 3003−3012.
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Basavarajappa, K. V. 6-Substituted benzothiazole based dispersed azo
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novel molecular design for solar cells. Appl. Surf. Sci. 2020, 501,
144054. (c) Gnida, P.; Pająk, A.; Kotowicz, S.; Malecki, J. G.; Siwy,
Lei Wang − Institute of Advanced Studies and School of
Pharmaceutical and Chemical Engineering, Taizhou
University, Taizhou 318000, P R China
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c02095
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support from the Leading Innovative and Entrepre-
neur Team Introduction Program of Zhejiang (no.
2019R01005) is gratefully acknowledged.
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