On Water: Metal-Free Synthesis of Highly Functionalized Benzothiazolylidene from ortho-Haloanilines

Article abstract of DOI:10.1021/acs.joc.8b03107

An environmentally benign, transition-metal-free organic base promoted one-pot cascade synthesis of highly functionalized benzo[d]thiazol-2(3H)-ylidene benzamide in the presence of water was accomplished by three-component reaction of ortho-iodoanilines,

Full text of DOI:10.1021/acs.joc.8b03107

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Article
On Water: Metal-free Synthesis of Highly Functionalized
Benzothiazolylidene from ortho-Haloanilines
Kapil Mohan Saini, Rakesh K. Saunthwal, Shiv Kumar, and Akhilesh K. Verma
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b03107 • Publication Date (Web): 31 Jan 2019
Downloaded from http://pubs.acs.org on January 31, 2019
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On Water: Metal-free Synthesis of Highly Functionalized
Benzothiazolylidene from ortho-Haloanilines
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Kapil Mohan Saini, Rakesh K. Saunthwal, Shiv Kumar and Akhilesh K. Verma*
Synthetic Organic Chemistry Research Laboratory, Department of Chemistry,
University of Delhi, Delhi–110007, India
Email: averma@acbr.du.ac.in
ABSTRACT: An environmentally benign, transition-metal-free organic base promoted one-pot
cascade synthesis of highly functionalized benzo[d]thiazol-2(3H)-ylidene benzamide in the
presence of water has been accomplished by three-component reaction of ortho-iodoanilines,
acrylates, and aroyl isothiocyanates. The protocol involves the in situ generation of thiourea
intermediate followed by triethylamine induced intramolecular SN displacement reaction and
Ar
subsequent Michael addition onto acrylate leads to the formation of benzo[d]thiazol-2(3H)-
ylidene benzamide. Benzo[b]thiazole is also generated in good yields using amidation and
intramolecular aromatic nucleophilic substitution chemistry. The control experiments support the
proposed mechanistic pathway. Further X-ray crystallographic studies confirm the assigned
structures of the fused benzamide.
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INTRODUCTION
Heterocyclic processes in nature frequently inspire the organic chemist to discover new organic
1
reactions for the synthesis of biologically active pharmacophores. Among various efforts
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committed towards the development of bio-active compounds, cascade process has appeared as
a potent synthetic tool in modern organic chemistry. The evolution of unique five-membered
heterocyclic framework is particularly important in drug discovery. In this perspective, the
benzothiazolylidene and benzothiazole core reserve privileged structure in medicinal chemistry
as antitumor agents, neuronal nicotinic receptor, anti-rotavirus infections, nuclear hormone
receptor, anti-infective herbicidal, anti-inflammatory, anti-viral, anticonvulsant, and
1
-4
cardiovascular activity (Figure 1).
Figure 1. Medicinally important thiazolylidene and benzothiazole cores.
Industrial chemical processes mainly emphasis on the use of a metal-catalyst strategy. Recent
years have validated great progress in the development of small ring heterocycles using tandem
5
and cascade approaches. In general, the transition metal catalyst is high- priced and often require
a supporting ligand which invents the overall process eco-unfriendly. As a result, the sustainable
development of metal-free catalysis is in high demand. Some improvements in the methodology
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for the formation of benzothiazoles via amidation chemistry have been described by many
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research groups. However, the synthesis of benzo[d]thiazol-2(3H)-ylidene in the absence of
7
metal and ligand is quite rare.
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Scheme 1. Previous Strategies vs Present Work
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In past decades Bao, and Smith III groups reported the synthesis of N-substituted-2-
aminobenzothiazoles from 2-haloanilines and isothiocyanates using 15 mol% copper (I) in
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DMSO at 95-115 C. In 2015, Marcus et al. demonstrated DBU promoted synthesis of 2-
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iminothiazolidines by employing substituted thioureas and allylic bromides (Scheme 1a).
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1a
Recently Dethe and co-workers developed a facile route for the synthesis of thiazolidine-2-
imines and thiazolidine-2-ylideneamine using catalytic chiral copper–pybox complex under
solvent-free conditions (Scheme 1b). In 2017, the same group reported an improved method for
the synthesis of thiazolidine-2-ylideneamines by thiol-yne coupling of propargylamine under
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1b
solvent-free condition by bond anion relay chemistry. In 2015, our group reported a green
protocol, for the synthesis of functionalized tetrahydroquinazolines from 2-aminophenylacrylate
12
with excellent chemoselectivity (Scheme 1c). Recently, Patel and co-workers reported an
interesting chemistry for the synthesis of quinoline-4(1H)-thiones from aroyl isothiocyanates and
o-alkynylanilines by a 6-exo-dig S-cyclization of the in situ generated thiourea followed by
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rearrangement (Scheme 1d). Despite novelty and versatility of reported methods, metal-free,
sustainable and operationally simple synthetic methods are still in demand. In continuation of our
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efforts on sustainable approaches for the synthesis of biologically useful molecules, herein we
have demonstrated the base-promoted one-pot synthesis of benzo[d]thiazol-2(3H)-ylidene
benzamides via amidation followed by intramolecular SN displacement and Michael-addition
Ar
reaction (Scheme 1e).
RESULTS AND DISCUSSION
A successful cascade synthesis of benzothiazolylidene required the catalytic system with
high efficiency and cost-effective reagents. With this objective, we started our investigation
using 2-iodoaniline 1a, benzoyl isothiocyanate 2a, and methyl acrylate 3a as our model
substrates (Table 1). The three component reaction of 2-iodoaniline 1a, benzoyl isothiocyanate
2
a with 3a using 10 mol% of bis(triphenylphosphine)palladium chloride and 2.5 equiv of
o
triethylamine in water for 20 h at 100 C, gave the benzothiazolylidene product 4a in 70% yield
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(
entry 1). Switching, the water to polar organic solvents such as DMF and DMSO, did not
provide the desired product 4a (entries 23).
a
Table 1. Optimization of the Bio-active Benzothiazolylidene
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b
yield (%)
entry
catalyst (mol %)
base (equiv) solvent
T (h) / t (°C)
4a
1
2
3
4
5
6
7
8
9
Pd(PPh ) Cl /10 Et N / 2.5
H O
20/100
20/100
20/100
20/90
20/90
24/90
24/70
20/90
24/90
24/90
24/90
24/90
24/90
20/90
70
3
2
2
3
2
c
Pd(PPh ) Cl /10 Et N / 2.5
DMF
00
3
2
2
3
c
Pd(PPh ) Cl /10 Et N / 2.5
DMSO
00
3
2
2
3
-
-
-
-
-
-
-
-
-
-
-
Et N / 2.5
H O
2
75
85
85
50
60
40
35
28
3
Et N / 3.0
H O
2
3
Et N / 3.0
H O
2
3
Et N / 3.0
H O
2
3
Et N / 2.0
H O
2
3
Cs CO / 2.0
H O
2
2
3
1
1
1
0
1
2
K CO /2.0
H O
2
2
3
Na CO /2.0
H O
2
2
3
d
KOH/2.0
-
H O
2
00
13
14
H O
2
00
e
Et N / 3.0
EtOH
15
3
a
Unless otherwise noted all reactions were carried out using 2-iodoaniline 1a (0.50 mmol),
benzoyl isothiocyanate 2a (0.52 mmol), methyl acrylate 3a (2.50 mmol), catalyst and base in 2
b
c
d
mL solvent, Isolated yield. Only urea intermediate was observed. Benzo[d]thiazole product
e
was observed. Along with benzo[d]thiazole product.
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An interesting result was observed when the reaction was carried out in the
absence of palladium catalyst; the product 4a was obtained in 75% yield (entry 4). To our
delight, the isolated yield was improved to 85% by decreasing the reaction temperature from 100
o
o
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C to 90 C (entry 5). On running the reaction for 24 h, didn’t affect the yield of the coupled
product 4a (entry 6). The further decrease in reaction temperature afforded the desired product
a in 50% yield (entry 7). Lowering the amount of Et N provided the cyclized product 4a in 60%
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yield (entry 8). Use of Cs CO K CO , and Na CO instead of Et N furnished the product 4a in
2
3,
2
3
2
3,
3
lower yield (entries 911). KOH provided the Benzo[d]thiazole product in 40% yield (entry 12).
It is noteworthy that no desired product 4a was obtained in the absence of a base (entry 13).
Ethanol gave product 4a in 15% yield along with benzo[d]thiazole product (entry 14).
Table 2. Synthesis of Benzothiazolylidene Benzamide
acyl iso-
thiocyanate 2
entry
1
anilines 1
alkenes 3
product 4
yield (%)
4a
85
84
3
a
2
a
1
a
1a
2a
4b
2
3b
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1a
1a
1a
1a
1a
2a
2a
2a
2a
4c
4d
4e
4f
82
78
3c
3d
3e
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b
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f
3a
4g
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1a
3a
3b
4h
4i
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4k
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2a
2a
3a
3b
4l
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85
1
b
1
1
3
4
1b
1b
4m
2a
2a
3c
4n
4o
83
79
1
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3d
b
1b
1b
2a
2b
3f
4p
4q
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1b
1b
2b
3c
4r
80
77
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0
1
2
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0
2b
2c
3d
3b
4s
4t
1b
1b
78
79
2
2
2
1
2
3
3b
3b
3d
3b
4u
4v
4w
4x
2
d
b
2a
2a
2b
70
65
72
1
c
b
1c
1c
b
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1c
2b
2a
3c
3f
4y
4z
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1
d
a
All reactions were carried out using aniline 1 (0.50 mmol), benzoyl isothiocyanate 2 (0.52
b
mmol), acrylate 3 (2.50 mmol), Et N (3.0 equiv) in 2 mL H O, Time 22 h
3
2
Having established the optimum reaction conditions, we next studied the substrate scope
and generality of the reaction using an eco-friendly approach (Table 2). Reaction of 2-
iodoaniline 1a, benzoyl isothiocyanate 2a and methyl acrylate 3a proceeded with an inclusive
conversion to gave the benzo[d]thiazol-2(3H)-ylidene benzamide 4a in 85% yield (Table 2,
entry 1). Ethyl (3b), n-butyl (3c) and tert-butyl (3d) acrylates with 2-iodoaniline 1a and benzoyl
isothiocyanate 2a afforded the desired products 4bd, in 7884% yields (entries 24). The
structures of the desired products 4c and 4d were further confirmed by the X-ray
1
5
crystallographic studies (See SI). N, N-Dimethylacrylamide 3e and acrylonitrile 3f were well
implemented in the reaction, providing the cyclized products 4ef in good yield (entries 56).
Para and meta-substituted benzoyl isothiocyanate 2bc delivered the products 4gk, in good
yield (entries 711). Our methodology was compatible with the combination of electron-rich 2-
iodo-5-methylaniline 1b and benzoyl isothiocyanate 2a with Michael acceptor olefins 3af
fruitfully provided the desired products 4lp, in 7086% yields (entries 1216). Electron-
donating aniline and isothiocyanate furnished the benzothiazolylidene products 4qt in 7782%
yield (entries 1720). Electron-deficient 3-chlorobenzoyl isothiocyanate 2d was well tolerated
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in the reaction to provide the cyclized product 4u in good yield (entry 21). Functional groups
such as 4-chloro and 4-fluoro substituted 2-iodoanilines afforded the desired product 4vz, in
6
572% yields (entries 2226).
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Scheme 2. Synthesis of Benzo[d]thiazole
Additionally, we explored the synthesis of benzo[d]thiazolyl using green approach
(
Scheme 2). The reaction was initiated with 2-iodoaniline 1a, benzoyl isothiocyanate 2a using
o
2.0 equiv. of Et N and water as a green solvent at 90 C for 4 h and the desired N-
3
(
benzo[d]thiazol-2-yl) benzamide 5a was observed in 89% yield. As depicted in Scheme 2, 4-
methylbenzoyl isothiocyanate was smoothly converted to product 5b in 90% yield. It is worthy
to note, electron-rich 2-iodoanilines provided the cyclized products 5cd, in 8688% yields. It
was found that the electron-withdrawing -F and -Cl substituted 2-iodoanilines were well
tolerated in this reaction, yielded the benzothiazolyl products 5ef in good yield. X-ray crystal
1
5
structure also confirmed the structure of product 5e (See SI).
Scheme 3. Mechanistic Control Experiments
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Now, our next effort was directed towards the mechanistic studies of the reactions
o
(Scheme 3). The reaction of 2-iodoanilines 1a with 2b in water at 90 C, afforded the urea
intermediate 6 (Scheme 3i). This urea adduct 6 was further employed with acrylate using 3.0
equiv of Et N in a green solvent, provided the benzothiazolylidene 4j; however, the simple
3
Michael adduct 7 was not formed (Scheme 3 ii). Benzo[d]thiazole 5a participated well with
acrylate 3a to provide the desired product 4a (Scheme 3 iii). All the above control experiments
suggested that the reaction goes via a cascade process.
Scheme 4. Plausible Reaction Pathway
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Based on the control experiments and literature studies, we proposed a plausible
mechanistic pathway in Scheme 4. The mechanism was initiated by the reaction of o-halo
anilines 1 with isothiocyanates 2 which leads to the formation of urea intermediate 6. With the
support of the base (Et N), intramolecular nucleophilic attack of sulphur on the ipso position of
3
iodobenzene occurs. The loss of iodine via an aromatic nucleophilic substitution reaction leads to
the formation of benzothiazolyl product 5. The regioselective olefin insertion at benzothiazolyl
nitrogen then generates the product 4 via a 1, 4-addition step.
CONCLUSIONS
In conclusion, we have developed an environmentally benign; operationally simple, catalyst-
free cascade approach for the synthesis of highly functionalized benzothiazolylidene benzamide
derviatives using mild reaction conditions with excellent regioselectivity in good to excellent
yields. Ortho-iodoanilines and aroyl isothiocyanates bearing electron-releasing and electron-
withdrawing groups successfully provided the desired products in good yields. Water is non-
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flammable and inexpensive solvent in contrast to other organic solvents, which show the
remarkable effect on the yield and rate of the organic reaction via hydrophobic interactions. The
developed chemistry can be used for the synthesis of benzo[d]thiazolyl derivatives from 2-
iodoaniline, benzoyl isothiocyanate through in situ formations of N-(phenylcarbamothioyl)
benzamide and concomitant intramolecular aromatic nucleophilic substitution reaction. We
anticipate that this protocol is useful for the synthesis of highly substituted benzothiazole
derivatives, which could find further application in the synthesis of the biologically active
compound.
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EXPERIMENTAL SECTION
General Information and Method. All the reactions were performed in an oven˗dried
Schlenk flask. Column chromatography was performed using silica gel (mesh 100˗200). TLC
analysis was performed on commercially prepared 60 F254 silica gel plates. Visualization of spots
1
on TLC plate was accomplished with UV light (254 nm) and staining over I chamber. H NMR
2
1
3
(
400 MHz) and C NMR (100 MHz) spectra were recorded in CDCl and (CD ) SO.Chemical
3 3 2
shifts for carbons are reported in ppm from tetramethylsilane and are referenced to the carbon
resonance of the solvent. Data are reported as follows: chemical shift, multiplicity (s = singlet, d
= doublet, t = triplet, q = quartet, m = multiplet, dd = doublet of doublet, br s = broad singlet),
coupling constants in Hertz, and integration. High-resolution mass spectra were recorded with
q−TOF electrospray mass spectrometer. All purchased chemicals were used as received. All
melting points are uncorrected.
General experimental procedure for green one-pot synthesis of benzo[d]thiazol-2(3H)-
ylidene benzamides 4a-z: To a solution of ortho-haloanilines 1 (0.5 mmol), aroyl
isothiocyanates 2 (0.52 mmol) in tap water (2.0 mL), acrylates 3 (2.5 mmol) and Et N (3.0
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equiv) were added. The reaction was then stirred at 90 °C until TLC revealed complete
conversion of the starting material. After the completion of the reactant, the reaction mixture was
then allowed to cool and diluted with H O and extracted with EtOAc (3X10 mL). The combined
2
1
1
1
1
1
1
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organic layers were dried over Na SO , concentrated under vacuum, and purified by column
2
4
chromatography using 100−200 mesh size silica gels (hexane) to afford the corresponding
product.
Methyl (E)-3-(2-(benzoylimino)benzo[d]thiazol-3(2H)-yl) propanoate (4a). The product was
o
1
obtained as a off white needles, mp: 140–142 C (144.5 mg, 85%); H NMR (400 MHz, DMSO-
d6) δ 8.268.24 (m, 2H), 7.75 (d, J = 8.2 Hz, 1H), 7.607.58 (m, 1H), 7.557.51 (m, 4H),
1
3
1
7
.507.46 (m, 1H), 4.80 (t, J = 6.6 Hz, 2H), 3.49 (s, 3H), 2.92 (t, J = 6.9 Hz, 2H); C{ H} NMR
(
100 MHz, DMSO-d ) δ 174.1, 170.9, 167.2, 136.7, 134.7, 133.7, 132.6, 129.8, 129.6, 129.1,
6
+
128.9, 126.2, 123.7, 123.2, 113.0, 52.1, 42.0, 32.1. HRMS (ESI) [M+H] Calcd for [C H N O S]
1
8
17
2
3
3
41.0960, found 341.0941.
Ethyl (E)-3-(2-(benzoylimino)benzo[d]thiazol-3(2H)-yl)propanoate (4b). The product was
o
1
obtained as a white needles, mp: 75–77 C (148.7 mg, 84%); H NMR (400 MHz, CDCl ) δ
3
8
.358.33 (m, 2H), 7.61 (d, J = 7.8 Hz, 1H), 7.507.47 (m, 1H), 7.457.38 (m, 4H), 7.257.21
(
m, 1H), 4.72 (t, J = 7.3 Hz, 2H), 4.06 (q, J = 7.3 Hz, 2H), 2.94 (t, J = 7.3 Hz, 2H), 1.14 (t, J = 7.3
1
3
1
Hz, 3H); C{ H} NMR (100 MHz, CDCl ) δ 174.8, 170.9, 167.0, 136.2, 136.0, 133.3, 131.9,
3
+
1
29.9, 129.4, 128.0, 126.8, 123.7, 122.8, 111.3, 60.9, 41.3, 32.2, 13.8. HRMS (ESI) [M+H]
Calcd for [C H N O S] 355.1116, found 355.1104.
1
9
19
2
3
Butyl (E)-3-(2-(benzoylimino)benzo[d]thiazol-3(2H)-yl)propanoate (4c). The product was
o
1
obtained as a white needles, mp: 69–71 C (156.6 mg, 82%); H NMR (400 MHz, DMSO–d ) δ
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.228.20 (m, 2H), 7.85 (d, J = 8.2 Hz, 1H), 7.69 (d, J = 8.7 Hz, 1H), 7.557.44 (m, 4H),
.327.29 (m, 1H), 4.75 (t, J = 6.4 Hz, 2H), 3.82 (t, J = 7.6 Hz, 2H), 2.87 (t, J = 8.2 Hz, 2H),
13
1
.351.28 (m, 2H), 1.121.03 (m, 2H), 0.69 (t, J = 7.1 Hz, 3H); C{ H} NMR (100 MHz,
0
1
2
3
4
5
6
7
8
9
0
1
2
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7
8
9
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2
3
4
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7
8
9
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2
3
4
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7
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DMSO–d ) δ 173.6, 170.7, 166.7, 136.2, 136.1, 132.1, 129.1, 128.3, 127.2, 125.7, 124.0, 123.1,
6
+
112.5, 64.1, 41.5, 32.1, 29.9, 18.5, 13.5. HRMS (ESI) [M+H] Calcd for [C H N O S]
21
23
2
3
3
83.1429, found 383.1401.
tert-Butyl (E)-3-(2-(benzoylimino)benzo[d]thiazol-3(2H)-yl) propanoate (4d). The product was
o
1
obtained as a white needles, mp: 133–135 C (149.0 mg, 78%); H NMR (400 MHz, CDCl ) δ
3
8.378.35 (m, 2H), 7.64 (d, J = 7.8 Hz, 1H), 7.507.48 (m, 1H), 7.467.42 (m, 4H), 7.287.24
13
1
(
m, 1H), 4.72 (t, J = 7.8 Hz, 2H), 2.87 (t, J = 8.7 Hz, 2H), 1.37 (s, 9H); C{ H} NMR (100 MHz,
CDCl ) δ 174.8, 170.1, 167.0, 136.3, 132.0, 129.6, 128.1, 126.6, 123.6, 122.8, 111.3, 81.4, 41.5,
3
+
33.5, 27.9, 27.8. HRMS (ESI) [M+H] Calcd for [C H N O S] 383.1429, found 383.1400.
21
23
2
3
(
E)-N-(3-(3-(dimethylamino)-3-oxopropyl)benzo[d]thiazol-2(3H)-ylidene)benzamide (4e). The
o
1
product was obtained as a white needles, mp: 119–121 C (114.7 mg, 65%); H NMR (400 MHz,
CDCl ) δ 8.348.32 (m, 2H), 7.65 (d, J = 7.8 Hz, 1H), 7.517.47 (m, 2H), 7.457.41 (m, 3H),
3
7
.287.25 (m, 1H), 4.81 (t, J = 7.8 Hz, 2H), 2.93 (t, J = 7.3 Hz, 2H), 2.91 (s, 3H), 2.87 (s, 3H);
1
3
1
C{ H} NMR (100 MHz, CDCl ) δ 175.1, 170.2, 167.3, 136.5, 136.46, 132.2, 129.6, 128.3,
3
+
1
27.2, 126.8, 124.0, 123.0, 111.8, 42.3, 37.3, 35.5, 31.0. HRMS (ESI) [M+H] Calcd for
[
C H N O S] 354.1276, found 354.1257.
19 20 3 2
(E)-N-(3-(2-cyanoethyl)benzo[d]thiazol-2(3H)-ylidene)benzamide (4f). The product was obtained
o
1
as a white needles, mp: 208–210 C (104.5 mg, 68%); H NMR (400 MHz, CDCl ) δ 8.338.31
3
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(
m, 2H), 7.71 (d, J = 7.8 Hz, 1H), 7.567.52 (m, 1H), 7.507.43 (m, 4H), 7.367.32 (m, 1H), 4.77
13
1
(t, J = 7.3 Hz, 2H), 3.08 (t, J = 7.3 Hz, 2H); C{ H} NMR (100 MHz, CDCl ) δ 174.9, 167.3,
3
140.4, 135.9, 135.6, 132.3, 129.5, 128.2, 127.3, 126.6, 124.4, 123.3, 116.9, 110.8, 41.1, 16.1.
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
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3
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5
5
5
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0
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1
2
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2
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1
2
3
4
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7
8
9
0
+
HRMS (ESI) [M+H] Calcd for [C H N OS] 308.0858, found 308.0856.
17
14
3
Methyl (E)-3-(2-((4-methylbenzoyl)imino)benzo[d]thiazol-3(2H)-yl)propanoate (4g). The product
o
1
was obtained as a white needles, mp: 146–148 C (141.6 mg, 80%); H NMR (400 MHz, CDCl )
3
δ 8.18 (d, J = 7.8 Hz, 2H), 7.61 (d, J = 7.8 Hz, 1H), 7.397.38 (m, 2H), 7.247.18 (m, 3H), 4.70
1
3
1
(t, J = 7.3 Hz, 2H), 3.59 (s, 3H), 2.92 (t, J = 7.3 Hz, 2H), 2.35 (s, 3H); C{ H} NMR (100 MHz,
CDCl ) δ 175.1, 171.6, 167.2, 142.7, 136.3, 133.8, 130.3, 129.7, 129.0, 127.0, 126.96, 123.9,
3
+
1
23.1, 111.4, 52.2, 41.5, 32.1, 21.8. HRMS (ESI) [M+H] Calcd for [C H N O S] 355.1116,
19
19
2
3
found 355.1108.
Methyl (E)-3-(2-((3-methylbenzoyl)imino)benzo[d]thiazol-3(2H)-yl)propanoate (4h). The product
o
1
was obtained as a white needles, mp: 90–92 C (136.3 mg, 77%); H NMR (400 MHz, CDCl ) δ
3
8
7
.158.14 (m, 2H), 7.64 (d, J = 7.8 Hz, 1H), 7.42 (d, J = 4.1 Hz, 2H), 7.337.31 (m, 2H),
.287.24 (m, 1H), 4.76 (t, J = 7.1 Hz, 2H), 3.63 (s, 3H), 2.96 (t, J = 6.9 Hz, 2H), 2.41 (s, 3H);
1
3
1
C{ H} NMR (100 MHz, CDCl ) δ 175.0, 171.3, 167.0, 137.6, 136.2, 136.1, 132.7, 130.0, 127.9,
3
+
1
27.2, 126.8, 126.7, 123.7, 122.9, 111.3, 52.0, 41.3, 31.9, 21.3. HRMS (ESI) [M+H] Calcd for
[
C H N O S] 355.1116, found 355.1118.
19 19 2 3
Ethyl (E)-3-(2-((4-methylbenzoyl)imino)benzo[d]thiazol-3(2H)-yl)propanoate (4i). The product
o
1
was obtained as a white needles, mp: 117–119 C (143.9 mg, 78%); H NMR (400 MHz, CDCl )
3
δ 8.24 (d, J = 8.2 Hz, 2H), 7.64 (d, J = 7.8 Hz, 1H), 7.447.42 (m, 2H), 7.287.23(m, 3H), 4.74 (t,
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2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
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6
J = 6.9 Hz, 2H), 4.08 (q, J = 7.3 Hz, 2H), 2.96 (t, J = 6.9 Hz, 2H), 2.40 (s, 3H), 1.17 (t, J = 7.3 Hz,
1
3
1
3
H); C{ H} NMR (100 MHz, CDCl ) δ 175.0, 171.2, 167.1, 142.6, 136.3, 133.8, 129.7, 129.68,
3
+
129.0, 128.1, 127.0, 123.9, 123.0, 111.5, 61.2, 41.5, 32.4, 21.7, 14.1. HRMS (ESI) [M+H] Calcd
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
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7
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3
4
5
6
7
8
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0
1
2
3
4
5
6
7
8
9
0
for [C H N O S] 369.1273, found 369.1273.
20
21
2
3
Butyl (E)-3-(2-((4-methylbenzoyl)imino)benzo[d]thiazol-3(2H)-yl)propanoate (4j). The product
o
1
was obtained as a white needles, mp: 166–168 C (173.1 mg, 87%); H NMR (400 MHz, CDCl )
3
δ 8.22 (d, J = 7.8 Hz, 2H), 7.63 (d, J = 7.8 Hz, 1H), 7.427.41 (m, 2H), 7.267.22 (m, 3H), 4.72
(t, J = 7.3 Hz, 2H), 4.02 (t, J = 6.9 Hz, 2H), 2.94 (t, J = 7.3 Hz, 2H), 2.38 (s, 3H), 1.531.46 (m,
13
1
2
1
H), 1.301.21 (m, 2H), 0.85 (t, J = 7.3 Hz, 3H); C{ H} NMR (100 MHz, CDCl ) δ 174.8,
3
71.0, 166.8, 142.4, 136.1, 133.6, 129.5, 128.7, 126.8, 126.7, 123.6, 122.8, 111.3, 64.9, 41.4,
+
32.2, 30.3, 21.5, 18.9, 13.5. HRMS (ESI) [M+H] Calcd for [C H N O S] 397.1586, found
22
25
2
3
3
97.1578.
tert-Butyl (E)-3-(2-((4-methylbenzoyl)imino)benzo[d]thiazol-3(2H)-yl)propanoate (4k). The
o
1
product was obtained as a white needles, mp: 139–141 C (150.5 mg, 76%); H NMR (400 MHz,
CDCl ) δ 8.24 (d, J = 7.8 Hz, 2H), 7.62 (d, J = 8.0 Hz, 1H), 7.417.38 (m, 2H), 7.267.22 (m,
3
1
3
1
3H), 4.68 (t, J = 6.9 Hz, 2H), 2.85 (t, J = 7.1 Hz, 2H), 2.38 (s, 3H), 1.37 (s, 9H); C{ H} NMR
(
100 MHz, CDCl ) δ 174.7, 170.1, 166.6, 142.3, 136.1, 133.6, 129.4, 128.7, 126.7, 126.6, 123.5,
3
+
1
22.7, 111.3, 81.2, 41.4, 33.4, 27.8, 21.5. HRMS (ESI) [M+H] Calcd for [C H N O S]
22
25
2
3
397.1586, found 397.1577.
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Methyl (E)-3-(2-(benzoylimino)-5-methylbenzo[d]thiazol-3(2H)-yl)propanoate (4l). The product
o
1
was obtained as a white needles, mp: 125–127 C (152.2 mg, 86%); H NMR (400 MHz, CDCl )
3
δ 8.378.35 (m, 2H), 7.557.44 (m, 4H), 7.24 (s, 1H), 7.11 (d, J = 7.8 Hz, 1H), 4.75 (t, J = 7.3
1
1
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0
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0
13
1
Hz, 2H), 3.67 (s, 3H), 2.97 (t, J = 7.8 Hz, 2H), 2.48 (s, 3H); C{ H} NMR (100 MHz, CDCl ) δ
3
1
74.8, 171.3, 167.5, 137.4, 136.3, 136.2, 133.3, 131.9, 130.0, 129.4, 128.0, 123.6, 122.6, 111.6,
+
52.0, 41.2, 31.9, 21.7. HRMS (ESI) [M+H] Calcd for [C H N O S] 355.1116, found 355.1112.
19
19
2
3
Ethyl (E)-3-(2-(benzoylimino)-5-methylbenzo[d]thiazol-3(2H)-yl)propanoate (4m). The product
o
1
was obtained as a white needles, mp: 141–143 C (156.4 mg, 85%); H NMR (400 MHz, CDCl )
3
δ 8.378.34 (m, 2H), 7.547.51 (m, 2H), 7.497.44 (m, 2H), 7.24 (s, 1H), 7.10 (d, J = 7.8 Hz,
1
H), 4.74 (t, J = 6.9 Hz, 2H), 4.11 (q, J = 7.3 Hz, 2H), 2.95 (t, J = 7.3 Hz, 2H), 2.47 (s, 3H), 1.19
1
3
1
(
t, J = 7.3 Hz, 3H); C{ H} NMR (100 MHz, CDCl ) δ 174.7, 170.9, 167.4, 137.3, 136.3, 136.2,
3
131.8, 129.4, 128.7, 128.0, 125.0, 123.5, 122.5, 111.7, 61.0, 41.3, 32.2, 21.7, 13.9. HRMS (ESI)
+
[
M+H] Calcd for [C H N O S] 369.1273, found 369.1256.
20
21
2
3
Butyl (E)-3-(2-(benzoylimino)-5-methylbenzo[d]thiazol-3(2H)-yl)propanoate (4n). The product
o
1
was obtained as a white needles, mp: 86–88 C (164.4 mg, 83%); H NMR (400 MHz, CDCl ) δ
3
8
.368.34 (m, 2H), 7.557.49 (m, 2H), 7.477.43 (m, 2H), 7.24 (s, 1H), 7.10 (d, J = 7.3 Hz, 1H),
.74 (t, J = 7.3 Hz, 2H), 4.06 (t, J = 6.4 Hz, 2H), 2.95 (t, J = 7.3 Hz, 2H), 2.48 (s, 3H), 1.571.50
4
1
3
1
(m, 2H), 1.341.24 (m, 2H), 0.87 (t, J = 7.3 Hz, 3H); C{ H} NMR (100 MHz, CDCl ) δ 174.8,
3
1
71.1, 167.5, 137.4, 136.4, 136.3, 131.9, 129.5, 128.0, 125.1, 125.05, 123.6, 122.6, 111.7, 111.68,
+
6
5.0, 41.4, 32.3, 30.4, 21.7, 19.0, 13.6. HRMS (ESI) [M+H] Calcd for [C H N O S] 397.1586,
22 25
2
3
found 397.1570.
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tert-Butyl(E)-3-(2-(benzoylimino)-5-methylbenzo[d]thiazol-3(2H)-yl)propanoate
(4o).
The
o
1
product was obtained as a white needles, mp: 138–140 C (156.5 mg, 79%); H NMR (400 MHz,
CDCl ) δ 8.378.35 (m, 2H), 7.547.49 (m, 2H), 7.477.43 (m, 2H), 7.24 (s, 1H), 7.09 (d, J = 8.2
3
0
1
2
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7
8
9
0
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4
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7
8
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0
13
1
Hz, 1H), 4.71 (t, J = 7.3 Hz, 2H), 2.86 (t, J = 7.3 Hz, 2H), 2.47 (s, 3H), 1.39 (s, 9H); C{ H}
NMR (100 MHz, CDCl ) δ 174.8, 170.2, 167.4, 137.3, 136.4, 136.36, 131.8, 129.5, 128.0, 125.0,
3
+
124.9, 123.6, 122.5, 111.9, 111.8, 81.4, 41.5, 33.6, 27.9, 21.7.HRMS (ESI) [M+H] Calcd for
[
C H N O S] 397.1586, found 397.1565.
22 25 2 3
(E)-N-(3-(2-cyanoethyl)-5-methylbenzo[d]thiazol-2(3H)-ylidene)benzamide (4p). The product
o
1
was obtained as a white needles, mp: 194–196 C (112.3 mg, 70%); H NMR (400 MHz, CDCl )
3
δ 8.298.27 (m, 2H), 7.547.48 (m, 2H), 7.467.42 (m, 2H), 7.19 (s, 1H), 7.12 (d, J = 7.8 Hz,
1
3
1
1
H), 4.71 (t, J = 7.3 Hz, 2H), 3.03 (t, J = 7.3 Hz, 2H), 2.47 (s, 3H); C{ H} NMR (100 MHz,
CDCl ) δ 174.8, 167.5, 137.8, 135.7, 132.6, 129.9, 128.8, 128.6, 127.7, 126.0, 125.1, 123.3,
3
+
1
22.4, 116.9, 111.6, 40.9, 22.1, 16.0. HRMS (ESI) [M+H] Calcd for [C H N OS] 322.1014,
18
16
3
found 322.1000.
Ethyl (E)-3-(5-methyl-2-((4-methylbenzoyl)imino)benzo[d]thiazol-3(2H)-yl)propanoate (4q). The
o
1
product was obtained as a white needles, mp: 151–153 C (156.6 mg, 82%); H NMR (400 MHz,
CDCl ) δ 8.22 (d, J = 8.2 Hz, 2H), 7.49 (d, J = 7.8 Hz, 1H), 7.247.19 (m, 3H), 7.06 (d, J = 8.2
3
Hz, 1H), 4.69 (t, J = 7.6 Hz, 2H), 4.09 (q, J = 7.3 Hz, 2H), 2.92 (t, J = 7.3 Hz, 2H), 2.45 (s, 3H),
1
3
1
2
1
1
.38 (s, 3H), 1.17 (t, J = 6.9 Hz, 3H); C{ H} NMR (100 MHz, CDCl ) δ 174.6, 170.9, 167.1,
3
42.2, 137.2, 136.2, 133.7, 129.4, 128.7, 124.9, 123.5, 122.4, 111.6, 60.9, 41.2, 32.2, 21.6, 21.5,
+
3.9; HRMS (ESI) [M+H] Calcd for [C H N O S] 383.1429, found 383.1400.
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Butyl (E)-3-(5-methyl-2-((4-methylbenzoyl)imino)benzo[d]thiazol-3(2H)-yl)propanoate (4r). The
o
1
product was obtained as a white needles, mp: 166–168 C (164.1 mg, 80%); H NMR (400 MHz,
CDCl ) δ 8.22 (d, J = 7.8 Hz, 2H), 7.50 (d, J = 7.8 Hz, 1H), 7.247.19 (m, 3H), 7.06 (d, J = 8.2
3
1
1
1
1
1
1
1
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1
1
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5
5
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0
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8
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Hz, 1H), 4.70 (t, J = 7.3 Hz, 2H), 4.04 (t, J = 6.9 Hz, 2H), 2.92 (t, J = 7.3 Hz, 2H), 2.45 (s, 3H),
1
3
1
2
.39 (s, 3H), 1.551.48 (m, 2H), 1.321.23 (m, 2H), 0.86 (t, J = 7.3 Hz, 3H); C{ H} NMR (100
MHz, CDCl ) δ 174.7, 171.0, 167.1, 142.3, 137.2, 136.3, 133.7, 129.5, 128.7, 124.9, 123.6, 122.5,
3
+
1
11.6, 64.9, 41.3, 32.2, 30.3, 21.7, 21.6, 18.9, 13.6; HRMS (ESI) [M+H] Calcd for
[
C H N O S] 411.1742, found 411.1731.
23 27 2 3
tert-Butyl (E)-3-(5-methyl-2-((4-methylbenzoyl)imino)benzo[d] thiazol-3(2H)-yl)propanoate (4s).
o
1
The product was obtained as a white needles, mp: 181–183 C (157.9 mg, 77%); H NMR (400
MHz, CDCl ) δ 8.26 (d, J = 8.2 Hz, 2H), 7.55 (d, J = 9.2Hz, 1H), 7.267.25 (m, 3H), 7.11 (d, J =
3
9.2 Hz, 1H), 4.73 (t, J = 7.8 Hz, 2H), 2.87 (t, J = 7.8 Hz, 2H), 2.50 (s, 3H), 2.42 (s, 3H), 1.40 (s,
13
1
9
1
H); C{ H} NMR (100 MHz, CDCl ) δ 174.9, 170.3, 167.3, 142.4, 137.3, 136.5, 133.9, 129.7,
3
+
28.9, 128.8, 125.1, 123.8, 122.7, 111.9, 81.5, 41.5, 33.6, 28.0, 21.7, 21.69; HRMS (ESI) [M+H]
Calcd for [C H N O S] 411.1742, found 411.1736.
2
3
27
2
3
Ethyl (E)-3-(5-methyl-2-((3-methylbenzoyl)imino)benzo[d]thiazol-3(2H)-yl)propanoate (4t). The
o
1
product was obtained as a white needles, mp: 145–147 C (149.0 mg, 78%); H NMR (400 MHz,
CDCl ) δ 8.048.02 (m, 2H), 7.387.35 (m, 1H), 7.237.18 (m, 2H), 7.08 (s, 1H), 6.956.93 (m,
3
1
H), 4.58 (t, J = 6.9 Hz, 2H), 3.97 (q, J = 7.3 Hz, 2H), 2.81 (t, J = 7.8 Hz, 2H), 2.32 (s, 3H), 2.30
1
3
1
(
s, 3H), 1.06 (t, J = 7.8 Hz, 3H); C{ H} NMR (100 MHz, CDCl ) δ 174.6, 170.7, 167.1, 137.4,
3
137.0, 136.1, 136.0, 132.4, 129.8, 127.7, 126.4, 124.8, 123.4, 122.2, 111.5, 60.7, 41.1, 32.1, 21.5,
+
2
1.2, 13.8; HRMS (ESI) [M+H] Calcd for [C H N O S] 383.1429, found 383.1419.
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Ethyl (E)-3-(2-((3-chlorobenzoyl)imino)-5-methylbenzo[d]thiazol-3(2H)-yl)propanoate (4u). The
o
1
product was obtained as a white needles, mp: 133–135 C (158.8 mg, 79%); H NMR (400 MHz,
CDCl ) δ 8.31 (s, 1H), 8.22 (d, J = 6.2Hz, 1H), 7.57 (d, J = 8.3 Hz, 1H), 7.497.47 (m, 1H),
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
7
.417.37 (m, 1H), 7.27 (s, 1H), 7.14 (d, J = 8.3 Hz, 1H), 4.77 (t, J = 7.3 Hz, 2H), 4.13 (q, J = 7.3
1
3
1
Hz, 2H), 2.96 (t, J = 7.3 Hz, 2H), 2.50 (s, 3H), 1.21 (t, J = 6.2 Hz, 3H); C{ H} NMR (100 MHz,
CDCl ) δ 173.5, 170.9, 167.9, 138.3, 137.6, 136.3, 134.2, 131.8, 129.6, 129.4, 127.6, 125.3,
3
+
1
23.6, 122.7, 111.9, 61.1, 41.5, 32.4, 21.8, 14.0; HRMS (ESI) [M+H] Calcd for [C H ClN O S]
2
0
20
2
3
4
03.0883, found 403.0858.
Ethyl (E)-3-(2-(benzoylimino)-6-chlorobenzo[d]thiazol-3(2H)-yl)propanoate (4v). The product
o
1
was obtained as a white needles, mp: 123–125 C (136.1 mg, 70%); H NMR (400 MHz, CDCl ) δ
3
8
.34 (d, J = 7.8 Hz, 2H), 7.66 (s, 1H), 7.567.52 (m, 1H), 7.497.45 (m, 2H), 7.437.42 (m, 2H),
4.74 (t, J = 6.9 Hz, 2H), 4.10 (q, J = 7.3 Hz, 2H), 2.99 (t, J = 7.3 Hz, 2H), 1.19 (t, J = 7.3 Hz, 3H);
13
1
C{ H} NMR (100 MHz, CDCl ) δ 175.1, 171.1, 167.1, 136.1, 135.1, 132.3, 129.7, 129.5, 128.5,
3
+
1
28.3, 127.4, 122.8, 112.6, 61.3, 41.9, 32.3, 14.1; HRMS (ESI) [M+H] Calcd for
[C H ClN O S] 389.0727, found 389.0723.
1
9
18
2
3
Butyl (E)-3-(2-(benzoylimino)-6-chlorobenzo[d]thiazol-3(2H)-yl)propanoate (4w). The product
o
1
was obtained as a white needles, mp: 78–80 C (135.5 mg, 65%); H NMR (400 MHz, CDCl ) δ
3
8.34 (d, J = 8.7 Hz, 2H), 7.65 (s, 1H), 7.567.52 (m, 1H), 7.487.45 (m, 2H), 7.427.41 (m, 2H),
4
.73 (t, J = 6.6 Hz, 2H), 4.04 (t, J = 6.4 Hz, 2H), 2.99 (t, J = 6.6 Hz, 2H), 1.561.49 (m, 2H),
13
1
1.331.24 (m, 2H), 0.87 (t, J = 7.3 Hz, 3H); C{ H} NMR (100 MHz, CDCl ) δ 175.1, 171.2,
3
1
1
67.1, 136.1, 135.1, 132.3, 129.7, 129.5, 128.5, 128.3, 127.4, 122.7, 112.6, 65.2, 41.9, 32.4, 30.5,
+
9.1, 13.7; HRMS (ESI) [M+H] Calcd for [C H ClN O S] 417.1040, found 417.1048.
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Ethyl (E)-3-(6-chloro-2-((4-methylbenzoyl)imino)benzo[d]thiazol-3(2H)-yl)propanoate (4x). The
o
1
product was obtained as a white needles, mp: 135–137 C (145.0 mg, 72%); H NMR (400 MHz,
CDCl ) δ 8.21 (d, J = 8.2 Hz, 2H), 7.63 (s, 1H), 7.39 (s, 2H), 7.25 (d, J = 7.3 Hz, 2H), 4.71 (t, J =
3
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
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4
4
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5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
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7
8
9
0
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.9 Hz, 2H), 4.09 (q, J = 7.3 Hz, 2H), 2.97 (t, J = 6.9 Hz, 2H), 2.41 (s, 3H), 1.18 (t, J = 7.6 Hz,
13
1
H); C{ H} NMR (100 MHz, CDCl ) δ 175.1, 171.1, 166.8, 142.9, 135.1, 133.5, 129.7, 129.4,
3
+
29.0, 128.5, 127.3, 122.7, 112.5, 61.3, 41.8, 32.3, 21.8, 14.1; HRMS (ESI) [M+H] Calcd for
[
C H ClN O S] 403.0883, found 403.0877.
20 20 2 3
Butyl (E)-3-(6-chloro-2-((4-methylbenzoyl)imino)benzo[d]thiazol-3(2H)-yl)propanoate (4y). The
o
1
product was obtained as a white needles, mp: 82–84 C (148.6 mg, 69%); H NMR (400 MHz,
CDCl ) δ 8.19 (d, J = 7.8 Hz, 2H), 7.60 (s, 1H), 7.377.36(m, 2H), 7.22 (d, J = 8.2 Hz, 2H), 4.68
3
(t, J = 7.1 Hz, 2H), 4.02 (t, J = 6.4 Hz, 2H), 2.95 (t, J = 6.9 Hz, 2H), 2.39 (s, 3H), 1.531.46 (m,
1
3
1
2
1
H), 1.281.23 (m, 2H), 0.85 (t, J = 7.6 Hz, 3H); C{ H} NMR (100 MHz, CDCl ) δ 175.1,
3
71.3, 166.8, 142.9, 135.1, 133.5, 129.7, 129.4, 129.0, 128.5, 127.3, 122.7, 112.5, 65.2, 41.9,
+
32.3, 30.5, 21.8, 19.1, 13.8; HRMS (ESI) [M+H] Calcd for [C H ClN O S] 431.1196, found
2
2
24
2
3
4
31.1205.
(E)-N-(3-(2-cyanoethyl)-6-fluorobenzo[d]thiazol-2(3H)-ylidene)benzamide (4z). The product was
o
1
obtained as a white needles, mp: 170–172 C (110.5 mg, 68%); H NMR (400 MHz, DMSO-d ) δ
6
8
.278.25 (m, 2H), 7.907.86 (m, 2H), 7.607.56 (m, 1H), 7.527.49 (m, 3H), 7.447.39 (m,
1
3
1
1H), 4.83 (t, J = 6.9 Hz, 2H), 3.17 (t, J = 6.2 Hz, 2H); C{ H} NMR (100 MHz, CDCl ) δ 175.1,
3
1
67.3, 159.7 (d, J = 245.6 Hz, 1C), 135.8, 132.6, 132.1, 129.6, 128.4, 116.9, 115.2 (d, J = 24.1
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+
Hz, 1C), 111.8 (d, J = 9.6 Hz, 1C), 110.4 (d, J = 26.0 Hz, 1C), 41.6, 16.3. HRMS (ESI) [M+H]
Calcd for [C H FN OS] 326.0763, found 326.0762.
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General experimental procedure for green one-pot synthesis of benzo[d]thiazolyl 5a-f: To a
solution of ortho-haloanilines 1 (0.5 mmol), aroyl isothiocyanates 2 (0.52 mmol) in tap water
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(
2.0 mL) Et N (2.0 equiv) was added. The reaction was then stirred at 90 °C until TLC revealed
3
complete conversion of the starting material. After the completion of the reactant, the reaction
mixture was then allowed to cool and diluted with H O and extracted with EtOAc (3X10 mL).
2
The combined organic layers were dried over Na SO , concentrated under vacuum, and purified
2
4
by column chromatography using 100−200 mesh size silica gels (hexane) to afford the
corresponding product.
N-(benzo[d]thiazol-2-yl)benzamide (5a). The product was obtained as a white needles, mp: 165–
o
1
1
7
67 C (113.1mg, 89%); H NMR (400 MHz, CDCl ) δ 12.10 (br s, 1H), 8.028.00 (m, 2H),
3
.83 (d, J = 7.8 Hz, 1H), 7.557.51 (m, 1H), 7.407.36 (m, 2H), 7.287.24 (m, 1H), 7.217.17
1
3
1
(
m, 1H), 7.107.08 (m, 1H); C{ H} NMR (100 MHz, CDCl ) δ 166.2, 160.0, 147.6, 133.0,
3
+
132.0, 131.8, 128.9, 128.0, 126.0, 124.0, 121.3, 120.6. HRMS (ESI) [M+H] Calcd for
[
C H N OS] 255.0592, found 255.0593.
14 11 2
N-(Benzo[d]thiazol-2-yl)-4-methylbenzamide (5b). The product was obtained as a white needles,
o
1
mp: 180–182 C (120.6 mg, 90%); H NMR (400 MHz, CDCl ) δ 11.73 (br s, 1H), 7.89 (d, J =
3
1
3
1
8
.8 Hz, 2H), 7.83–7.80 (m, 1H), 7.28–7.17 (m, 5H), 2.36 (s, 3H); C{ H} NMR (100 MHz,
CDCl ) δ 166.1, 160.0, 147.9, 143.9, 132.0, 129.7, 129.3, 128.1, 126.0, 123.9, 121.4, 120.8, 21.7.
3
+
HRMS (ESI) Calcd for [M+H] Calcd for [C H N OS] 269.0749, found 269.0750.
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N-(5-methylbenzo[d]thiazol-2-yl)benzamide (5c).The product was obtained as a white needles,
o
1
mp: 195–197 C (117.9 mg, 88%); H NMR (400 MHz, CDCl ) δ 12.47 (br s, 1H), 8.00 (d, J =
3
8.6 Hz, 2H), 7.66 (d, J = 8.6 Hz, 1H), 7.52 (t, J = 6.8 Hz, 1H), 7.37 (t, J = 7.7 Hz, 2H), 7.05 (d, J
1
3
1
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
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0
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0
=
7.7 Hz, 1H), 6.64 (s, 1H), 2.18 (s, 3H); C{ H} NMR (100 MHz, CDCl ) δ 166.4, 160.4,
3
1
47.7, 135.9, 132.8, 132.3, 128.9, 128.5, 128.2, 128.0, 127.3, 125.4, 120.7, 21.3. HRMS (ESI)
+
[
M+H] Calcd for [C H N OS] 269.0749, found 269.0734.
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3-Methyl-N-(5-methylbenzo[d]thiazol-2-yl)benzamide (5d).The product was obtained as a white
o
1
needles, mp: 212–214 C (114.3 mg, 81%); H NMR (400 MHz, CDCl ) δ 12.30 (br s, 1H), 7.74
3
(d, J= 7.8 Hz, 1H), 7.72–7.68 (m, 3H), 7.44–7.37 (m, 2H), 6.86–6.83 (m, 1H), 2.42 (s, 3H), 2.34
13
1
(
s, 3H); C{ H} NMR (100 MHz, CDCl ) δ 166.9, 159.9, 139.4, 139.1, 138.9, 138.86, 134.5,
3
+
1
31.3, 130.0, 129.0, 128.5, 128.2, 124.6, 21.3, 20.98. HRMS (ESI) [M+H] Calcd for
[C H N OS] 283.0905, found 283.0890.
1
6
15
2
N-(6-fluorobenzo[d]thiazol-2-yl)benzamide (5e).The product was obtained as a white needles,
o
1
mp: 191–193 C (112.8 mg, 83%); H NMR (400 MHz, CDCl ) δ 12.04 (br s, 1H), 8.04 (d, J =
3
8.8 Hz, 2H), 7.627.56 (m, 1H), 7.537.49 (m, 1H), 7.467.42 (m, 2H), 7.187.14 (m, 1H),
13
1
7
1
.016.96 (m, 1H); C{ H} NMR (100 MHz, CDCl ) δ 166.0, 159.8, 159.5 (d, J = 237.7 Hz,
3
C), 143.9, 133.2, 132.7 (d, J = 10.5 Hz, 1C), 131.7, 130.0, 129.0, 128.0, 121.3, 114.5 (d, J = 24.9
+
Hz, 1C), 107.8 (d, J = 4.8 Hz, 1C), 107.5 (d, J = 3.8 Hz, 1C). HRMS (ESI) [M+H] Calcd for
[
C H FN OS] 273.0498, found 273.0500.
14 10 2
N-(6-Chlorobenzo[d]thiazol-2-yl)benzamide (5f).The product was obtained as a white needles,
o
1
mp: 223–225 C (112.3 mg, 78%); H NMR (400 MHz, CDCl ) δ 10.99 (br s, 1H), 8.13 (s, 1H),
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.00 (d, J = 7.3 Hz, 2H), 7.647.61 (m, 1H), 7.577.55 (m, 1H), 7.527.48 (m, 3H); C{ H}
NMR (100 MHz, CDCl ) δ 165.6, 161.4, 150.3, 133.5, 132.2, 131.5, 129.2, 127.8, 123.3, 120.9,
3
+
119.2. HRMS (ESI) [M+H] Calcd for [C H ClN OS] 289.0202, found 289.0190.
1
4
10
2
0
1
2
3
4
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6
7
8
9
0
1
2
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9
0
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N-((2-iodophenyl)carbamothioyl)-4-methylbenzamide (6). The product was obtained as an off
o
1
white needles, mp: 160–162 C (188.6 mg, 95%); H NMR (400 MHz, CDCl ) δ 12.38 (s, 1H),
3
9
2
1
.22 (s, 1H), 7.907.86 (m, 2H), 7.817.79 (m, 2H), 7.40 (t, J = 7.3 Hz, 1H), 7.31 (d, J = 7.3 Hz,
1
3
1
H), 7.036.99 (m, 1H), 2.42 (s, 3H); C{ H} NMR (100 MHz, CDCl ) δ 179.7, 166.6, 144.8,
3
+
39.7, 139.3, 129.7, 128.8, 128.4, 127.8, 127.6, 127.3, 95.5, 21.6; HRMS (ESI) [M+H] Calcd for
[
C H IN OS] 396.9872, found 396.9880.
15 14 2
Supporting Information Available: The Supporting Information is available free of charge on
the ACS Publications website at DOI: .
1
13
1
H, C{ H} and HRMS spectra of synthesized compounds and XRay data (PDF)
X-ray crystallographic data of compounds 4c, 4d, and 5e (CIF).
AUTHOR INFORMATION
Corresponding Author
*
E-mail: averma@acbr.du.ac.in.
ORCID
Akhilesh K. Verma: 0000-0001-7626-5003
Notes
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The authors declare no competing financial interest.
Acknowledgement: We gratefully acknowledge the DST-SERB and CSIR for financial support
and USIC, the University of Delhi for providing instrumentation facilities. K.M.S., R.K.S. and
S.K. are thankful to CSIR for fellowship.
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