One-pot synthesis of highly functionalized benzo [1,3] thiazine from isocyanides, aniline, and heterocumulene via Cu-catalyzed intramolecular C-H activation reactions

Article abstract of DOI:10.1002/jccs.201800493

A one-pot synthesis of functionalized benzo thiazine derivatives via a Cu-catalyzed, multicomponent reaction of isocyanides, aniline, and heterocumulenes in acetonitrile at room temperature was developed. Transition metal-catalyzed activation of C-H bonds

Full text of DOI:10.1002/jccs.201800493

Received: 26 December 2018
DOI: 10.1002/jccs.201800493
Accepted: 31 March 2019
A R T I C L E
One-pot synthesis of highly functionalized benzo [1,3] thiazine
from isocyanides, aniline, and heterocumulene via Cu-catalyzed
intramolecular C-H activation reactions
Hossein F. Dastjerdi1 | Manijeh Nematpour1 | Elham Rezaee1 | Mehdi Jahani2
Sayyed A. Tabatabai1
|
1Department of Pharmaceutical Chemistry,
School of Pharmacy, Shahid Beheshti
Abstract
University of Medical Sciences, Tehran, Iran
A one-pot synthesis of functionalized benzo thiazine derivatives via a Cu-catalyzed,
2Department of Chemistry, Sharif University
of Technology, Tehran, Iran
multicomponent reaction of isocyanides, aniline, and heterocumulenes in acetoni-
trile at room temperature was developed. Transition metal-catalyzed activation of
C-H bonds under mild copper-catalytic reaction conditions, using simple and avail-
able starting materials, also obtaining a pure product with high yield without apply-
ing column chromatography are the major advantages of the applied method
among the other ones used for this purpose. The structures are confirmed spectro-
scopically (1H- and 13C-NMR, IR, and EI-MS) and through elemental analyses.
Correspondence
Sayyed A. Tabatabai, Department of
Pharmaceutical Chemistry, School of
Pharmacy, Shahid Beheshti University of
Medical Sciences, Tehran, Iran.
Email: sa_tabatabai@sbmu.ac.ir
Funding information
K E Y W O R D S
National Institute for Medical Research
Development (NIMAD), Grant/Award
Number: 962440
aniline, benzo [1, 3] thiazine, C-H activation, copper iodide, heterocumulene, isocyanides
the pharmaceutical industry.[14,15] Among various methods,
transition metal-catalyzed activation of C-H bonds is an effec-
1 | INTRODUCTION
1,3-Thiazines are attractive heterocycles in the fields of medic-
inal and pharmaceutical chemistry and have a variety of bio-
logical properties such as fungicidal, antitumor, and
antibacterial.[1,2] Among these cores, the benzothiazine deriva-
tives are so considerable because of their anti-inflammatory,[3]
antihypertensive,[4] antibacterial,[5,6] fungicidal,[7] and antip-
roliferative[8] activities. Therefore, synthesis and study of phar-
maceutical and biological effects of these heterocyclic
compounds are of pharmacological interest.
There are some reported methods for synthesis of
benzothiazines in the literature but most of them have some dis-
advantages, for example low yields, use of hazardous organic
solvents, strongly acidic conditions, tedious workup proce-
dures, etc.[9–13] Therefore, development of effective synthetic
methods with acceptable protocols is still desirable. The ortho
C-H functionalization of aromatic compound is of considerable
current interest for the synthesis of heterocyclic compounds in
tive and major topic for this purpose.[16–18] Formerly, our
research group has reported various multicomponent reactions
(MCRs) for creating new heterocyclic compounds with the
copper-catalyzed C-H activation reaction.[19–22] In this study, a
novel protocol for the synthesis of some benzothiazine deriva-
tives with good yields by a copper-catalyzed, one-pot three
component reaction of aniline 2, isocyanides 4, and
heterocumulene 1 derivatives was reported (see Scheme 1).
Comparison between the conventional and the presented
method shows that our method has appreciable advantages
such as mild reaction conditions, simple workup procedures,
shorter reaction time, and purer products in high yields.
2 | RESULTS AND DISCUSSION
To obtain optimal catalysis conditions, various catalysts, sol-
vents and bases along with aniline, CS2 and isocyanides as
© 2019 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
J Chin Chem Soc. 2019;1–5.
http://www.jccs.wiley-vch.de
1

2
DASTJERDI ET AL.
with various electron-withdrawing or electron-donating sub-
stituents on the aromatic rings (see Table 2).
The structures of compounds 5a-j were assigned by
1
mass, H NMR, 13C NMR, and IR spectral data. The mass
spectrum of 5a displayed the molecular ion peak at m/
1
z = 348. The H NMR spectrum of 5a exhibited one singlet
for the NH group (δ = 5.87 ppm), and along with character-
istic multiplets for the phenyl protons. The 13C NMR spec-
trum of 5a exhibited 12 signals in agreement with the
proposed structure. The NMR spectra of other compounds
5b-j were alike to those of 5a.
A possible mechanism for product formation is shown in
Scheme 2. It has been suggested that the reaction of CuI
with L-proline combines a five-membered chelate A. The
chelation of Cu (I) with the SH moiety of nucleophilic
adduct 3 (generated from 1 and 2) under the oxidative addi-
tion reaction conditions afforded the intermediate B. In the
end, the intermediate B by Cu-coordinated isocyanide car-
bon atom 5 becomes stable. Reductive elimination of B gave
the product 5 leaving the chelate A and the catalyst.
SCHEME 1 Synthesis of various benzo [1, 3] thiazine
derivatives by the Cu-catalyzed intramolecular C-H activation reaction
of isocyanides, aniline, and heterocumulene
the model substrates were tested. As shown in Table 1, CuI
was found to be the most effective catalyst among the cop-
per salts, CuI, CuBr, CuCl, Cu(OAc)2, and CuSO4 (10 mol
% amount) and Cs2CO3 gave the best results among several
bases such as Cs2CO3, K2CO3, KOt-Bu, NaOH, and KOH.
Also, MeCN was screened as the best solvent for this reac-
tion. Therefore, the reaction is checked out in MeCN by
using 10 mol% of CuI as the catalyst, 1.5 mmol of Cs2CO3
as the base, 20 mol% of L-proline as the ligand, 1.5 mmol of
isocyanides, 1.0 mmol of aniline, and 3.0 mmol of CS2 at
room temperature (see Table 1).
3 | EXPERIMENTAL
Using the optimized conditions described above, various
benzo [1, 3] thiazine derivatives were synthesized from CuI
as the catalyst, Cs2CO3 as the base, L-proline as the ligand,
carbon disulfide or isothiocyanate, isocyanides, and anilines
Melting points (m.p) were measured on an Electrothermal
9,100 apparatus. Elemental analyses were performed using a
Heraeus CHN-O-Rapid analyzer. The IR spectra were
recorded using a Shimadzu IR-460 spectrometer. The mass
spectra were obtained using a FINNIGAN-MAT 8430 mass
TABLE 1 Optimization of reaction conditions for the formation
of product 5a from 1.5 mmol of isocyanides, 3.0 mmol of carbon
disulfide, 1.0 mmol of aniline, 10 mol% of copper salt as the catalyst,
and 1.5 mmol of the base, 20 mol% of L-proline as the ligand
1
spectrometer of 70 eV. The H NMR (500.1 MHz) and 13C
NMR (125.7 MHz) spectra were obtained on a BRUKER
DRX 500-AVANCE FT-NMR instrument with CDCl3 as a
Entry
1b
2
Catalyst
CuI
Solvent
MeCN
Acetone
DMF
Base
Yield (%)a
TABLE 2 Synthesis of various benzo [1, 3] thiazine derivatives
Cs2CO3
NaOH
Cs2CO3
KOt-Bu
K2CO3
KOH
88
60
61
70
41
72
64
35
31
34
20
18
21
–
CuI
3
CuI
4
CuI
Acetone
THF
5
CuCl
CuCl
CuBr
CuBr
CuBr
Cu(OAc)2
Cu(OAc)2
CuSO4
CuSO4
–
Yield of
5 (%)
Compound R1
R2
H
X
6
Acetone
MeCN
Acetone
DMF
7
KOt-Bu
KOH
5a
5b
5c
5d
5e
5f
4-Br-C6H4
S
88
8
Ph
Ph
Cl
Me
S
90
9
NaOH
KOt-Bu
Cs2CO3
K2CO3
Cs2CO3
Cs2CO3
S
79
10
11
12
13
14
MeCN
Acetone
THF
4-Br-C6H4 OMe
Ph
4-Br-C6H4 Me
S
80
H
N-C6H5
N-C6H5
N-4-BrC6H4
85
81
MeCN
MeCN
5g
5h
5i
H
H
89
Ph
Ph
Ph
Br
Me
N-4-NO2C6H4 87
N-4-NO2C6H4 82
Note: bold items are the best reagents and afforded the highest yield.
aReaction time 5 hr.
b5 mol% catalyst, reaction time was 8 hr.
5j
OMe N-4-NO2C6H4 77

DASTJERDI ET AL.
3
NMR (500 MHz, CDCl3): δH = 6.07 (s, 1 H, NH), 7.21 (d,
3J = 7.6 Hz, 2 H, Ar), 7.26 (t, 3J = 7.6 Hz, 1 H, Ar), 7.34 (t,
3
3J = 7.6 Hz, 2 H, Ar), 7.62 (d, J = 7.9 Hz, 1 H, Ar), 7.74
3
(s, 1 H, Ar), and 8.04 (d, J = 7.9 Hz, 1 H, Ar). 13C-NMR
(125.7 MHz, CDCl3): δC = 126.2 (2 CH), 127.4 (CH), 127.7
(CH), 130.0 (CH), 130.1 (CH), 131.6 (2 CH), 135.6 (C),
144.8 (C), 145.6 (C), 153.1 (C), 167.8 (C=N), and 194.9
(C=S). MS: m/z (%) = 306 (M + 2, 4), 304 (8), 226 (16),
194 (32), 111 (100), and 77 (25). Anal. Calc. for
C14H9ClN2S2: C, 55.16; H, 2.98; and N, 9.19; Found: C,
55.18; H, 3.00; and N, 9.14.
SCHEME 2 Possible mechanism for the preparation of compound 5
solvent. All solvents and reagents were purchased from
Merck without purification.
3.4 | 6-Methyl-4-(phenylimino)-1H-benzo[d]
[1,3]thiazine-2(4H)-thione (5c)
White powder; yield: 0.22 g (79%); mp: 165–167ꢀC. IR
(KBr) (νmax, cm−1): 3233, 1,621, 1,201, and 1,108. 1H-
NMR (500 MHz, CDCl3): δH = 2.48 (s, 3 H, Me), 6.17 (s,
1 H, NH), 7.22 (d, 3J = 7.7 Hz, 2 H, Ar), 7.29 (t,
3.1 | General procedure for preparation of
compounds 5
A mixture of CS2 (3.0 mmol) or isothiocyanate (1.5 mmol)
1 and aniline 2 (1.5 mmol) in MeCN (2 mL) was stirred for
10 min. Then, a mixture of isocyanides 4 (1.5 mmol),
Cs2CO3 (1.5 mmol), CuI (0.10 mmol), and 20 mol% of L-
proline in MeCN (2 mL) was slowly added to the first solu-
tion and the reaction mixture was stirred for 5 hr. and the
reaction progression was monitored by TLC (AcOEt/ hexane
1:5), the mixture was stirred for 20 min by adding aqueous
NH4Cl solution (3 mL) and CH2Cl2 (2 mL). And then, the
layers were separated. Under reduced pressure, the aqueous
layer was concentrated. The final solid product was washed
with diethyl ether.
3
3J = 7.7 Hz, 1 H, Ar), 7.33 (t, J = 7.7 Hz, 2 H, Ar), 7.41
3
(d, J = 8.0 Hz, 1 H, Ar), 7.49 (s, 1 H, Ar), and 7.91 (d,
3J = 8.0 Hz, 1 H, Ar). 13C-NMR (125.7 MHz, CDCl3):
δC = 32.2 (Me), 122.5 (C), 126.2 (2 CH), 127.5 (CH), 127.7
(2 CH), 130.0 (2 CH), 130.6 (CH), 131.6 (C), 143.8 (C),
147.2 (C), 167.5 (C=N), and 195.2 (C=S). MS: m/z (%)
= 284 (M+, 7), 207 (21), 194 (38), 91 (100), and 77 (27).
Anal. Calc. for C15H12N2S2: C, 63.35; H, 4.25; and N, 9.85;
Found: C, 63.37; H, 4.20; and N, 9.88.
3.5 | 4-(4-Bromophenyl)imino-6-methoxy-1H-
benzo[d][1,3]thiazine-2(4H)-thione (5d)
Cream powder; yield: 0.30 g (80%); mp: 160–163ꢀC. IR
(KBr) (νmax, cm−1): 3215, 1,671, 1,213, and 1,103. 1H-
NMR (500 MHz, CDCl3): δH = 3.64 (s, 3 H, OMe), 5.92 (s,
3.2 | 4-((4-Bromophenyl)imino)-1H-benzo[d]
[1,3]thiazine-2(4H)-thione (5a)
White powder; yield: 0.31 g (88%); mp: 178–180ꢀC. IR
(KBr) (νmax, cm−1): 3201, 1,634, 1,220, and 1,100. 1H-
NMR (500 MHz, CDCl3): δH = 5.87 (s, 1 H, NH), 7.08 (d,
3J = 8.0 Hz, 2 H, Ar), 7.19 (t, 3J = 7.7 Hz, 1 H, Ar),
3
1 H, NH), 7.21 (d, J = 7.8 Hz, 1 H, Ar), 7.28 (s, 1 H, Ar),
3
7.32-7.36 (m, 4 H, Ar), and 7.50 (d, J = 8.0 Hz, 1 H, Ar).
13C-NMR (125.7 MHz, CDCl3): δC = 55.0 (OMe), 126.2
(2 CH), 127.8 (CH), 128.8 (CH), 129.3 (CH), 130.0 (C),
132.5 (2 CH), 141.0 (C), 143.3 (C), 145.7 (C), 149.9 (C),
167.6 (C=N), and 195.3 (C=S). MS: m/z (%) = 378 (M+,
6), 271 (16), 207 (15), 154 (63), 91 (100), and 77 (21). Anal.
Calc. for C15H11BrN2OS2: C, 47.50; H, 2.92; and N, 7.39;
Found: C, 47.53; H, 2.97; and N, 7.41.
3
7.30–7.35 (m, 3 H, Ar), and 7.50 (d, J = 8.0 Hz, 2 H, Ar).
13C-NMR (125.7 MHz, CDCl3): δC = 122.5 (C), 125.1
(2 CH), 126.2 (CH), 128.7 (CH), 129.3 (CH), 130.0 (CH),
132.5 (2 CH), 134.0 (C), 142.2 (C), 148.1 (C), 161.0
(C=N), and 196.1 (C=S). MS: m/z (%) = 348 (M+, 5),
271 (43), 192 (12), 154 (100), and 77 (52). Anal. Calc. for
C14H9BrN2S2: C, 48.14; H, 2.60; and N, 8.02; Found: C,
48.12; H, 2.63; and N, 8.00.
3.6 | (1H-Benzo[d][1,3]thiazine-2,4-diylidene)
dianiline (5e)
3.3 | 6-Chloro-4-(phenylimino)-1H-benzo[d]
[1,3]thiazine-2(4H)-thione (5b)
Cream powder; yield: 0.28 g (85%); mp: 140–143ꢀC. IR
(KBr) (νmax, cm−1): 3216, 1,645, 1,633, 1,210, and 1,121.
1H-NMR (500 MHz, CDCl3): δH = 6.07 (s, 1 H, NH),
White powder; yield: 0.27 g (90%); mp: 163–165ꢀC. IR
(KBr) (νmax, cm−1): 3233, 1,651, 1,220, and 1,123. 1H-
7.29-7.36 (m, 7 H, Ar), 7.40 (d, J = 8.0 Hz, 1 H, Ar),
3

4
DASTJERDI ET AL.
3
1
7.47-7.51 (m, 4 H, Ar), 7.60 (t, J = 7.8 Hz, 1 H, Ar), and
7.97 (d, 3J = 8.0 Hz, 1 H, Ar). 13C-NMR (125.7 MHz,
CDCl3): δC = 122.6 (C), 127.5 (2 CH), 128.7 (2 CH), 129.2
(2 CH), 129.3 (CH), 129.4 (CH), 130.7 (2 CH), 132.6
(2 CH), 134.3 (2 CH), 134.4 (C), 142.1 (C), 147.2 (C),
155.7 (C=N), and 157.9 (C=N). MS: m/z (%) = 329 (M+,
12), 253 (18), 194 (100), and 77 (48). Anal. Calc. for
C20H15N3S: C, 72.92; H, 4.59; and N, 12.76. Found: C,
72.95; H, 4.56; and N, 12.80.
and 1,200. H-NMR (500 MHz, CDCl3): δH = 6.08 (s, 1 H,
3
3
NH), 7.21 (d, J = 7.8 Hz, 2 H, Ar), 7.27 (t, J = 7.8 Hz,
1 H, Ar), 7.30-7.36 (m, 4 H, Ar), 7.49 (d, J = 8.1 Hz, 2 H,
3
3
3
Ar), 7.63 (t, J = 7.7 Hz, 2 H, Ar), and 8.05 (d, J = 8.0,
1 H, Ar). 13C-NMR (125.7 MHz, CDCl3): δC = 122.6 (C),
126.2 (2 CH), 127.4 (2 CH), 127.8 (CH), 128.7 (2 CH),
129.2 (CH), 130.0 (2 CH), 130.1 (CH), 132.5 (C), 135.7
(CH), 144.9 (C), 144.9 (C), 147.8 (C), 149.9 (C), 155.1
(C=N), and 160.0 (C=N). MS: m/z (%) = 452 (M+, 6),
374 (27), 329 (33), 154 (100), 122 (47), 91 (37), and
77 (25). Anal. Calc. for C20H13BrN4O2S: C, 52.99; H, 2.89;
and N, 12.36; Found: C, 52.93; H, 2.84; and N, 12.35.
3.7 | 4-Bromo-N-(6-methyl-2-(phenylimino)-
1H-benzo[d][1,3]thiazine-4(2H)-ylidene)
aniline (5f)
Cream powder; yield: 0.34 g (81%); mp: 169–171ꢀC. IR
(KBr) (νmax, cm−1): 3218, 1,615, 1,600, 1,221, and 1,104.
1H-NMR (500 MHz, CDCl3): δH = 2.44 (s, 3 H, Me), 5.57
(s, 1 H, NH), 7.10 (d, 3J = 7.8 Hz, 2 H, Ar), 7.22 (t,
3J = 7.8 Hz, 1 H, Ar), 7.32-7.39 (m, 6 H, Ar), 7.52 (d,
3.10 | N-(6-Methyl-4-(phenylimino)-1H-benzo
[d][1,3]thiazine-2(4H)-ylidene)-
4-nitroaniline (5i)
Pale yellow powder; yield: 0.32 g (82%); mp: 203–205ꢀC.
IR (KBr) (νmax, cm−1): 3221, 1,672, 1,632, 1,534, 1,342,
and 1,215. 1H-NMR (500 MHz, CDCl3): δH = 2.48 (s, 3 H,
Me), 6.13 (s, 1 H, NH), 7.22 (d, 3J = 7.8 Hz, 2 H, Ar), 7.29
3
3J = 7.8 Hz, 2 H, Ar), and 7.93 (d, J = 8.0 Hz, 1 H, Ar).
13C-NMR (125.7 MHz, CDCl3): δC = 31.7 (Me), 122.2 (C),
124.8 (2 CH), 125.8 (CH), 127.1 (2 CH), 128.4 (CH), 129.0
(CH), 129.9 (CH), 130.3 (2 CH), 132.2 (2 CH), 133.4 (C),
136.3 (C), 141.7 (C), 144.3 (C), 147.0 (C), 154.8 (C=N),
and 159.7 (C=N). MS: m/z (%) = 421 (M+, 5), 343 (22),
266 (30), 154 (100), 91 (100), and 77 (40). Anal. Calc. for
C21H16BrN3S: C, 59.72; H, 3.82; and N, 9.95; Found: C,
59.76; H, 3.85; and N, 9.99.
3
(t, J = 7.8 Hz, 1 H, Ar), 7.33-7.36 (m, 5 H, Ar), 7.40
3
3
(d, J = 7.8 Hz, 1 H, Ar), 7.50 (d, J = 8.0 Hz, 2 H, Ar),
and 7.92 (d, J = 8.0 Hz, 1 H, Ar). 13C-NMR (125.7 MHz,
3
CDCl3): δC = 32.2 (Me), 122.6 (C), 126.2 (2 CH), 127.5
(CH), 127.7 (2 CH), 128.9 (2 CH), 129.2 (2 CH), 130.6
(CH), 132.6 (2 CH), 132.9 (C), 140.1 (C), 142.1 (C), 147.2
(C), 148.4 (C), 154.2 (C=N), and 160.7 (C=N). MS: m/z
(%) = 388 (M+, 4), 311 (21), 266 (29), 122 (43), 91 (100),
and 77 (87). Anal. Calc. for C21H16N4O2S: C, 64.93; H,
4.15; and N, 14.42; Found: C, 64.95; H, 4.18;
and N, 14.46.
3.8 | 4-Bromo-(N- 4-(phenylimino)-1H-benzo
[d][1,3]thiazine-2(4H)-ylidene)aniline (5g)
Cream powder; yield: 0.36 g (89%); mp: 182–184ꢀC. IR
(KBr) (νmax, cm−1): 3232, 1,644, 1,602, 1,211, and 1,100.
1H-NMR (500 MHz, CDCl3): δH = 6.27 (s, 1 H, NH), 7.09
3
3
3.11 | N-(6-Methoxy-4-(phenylimino)-1H-
benzo[d][1,3]thiazine-2(4H)-ylidene)-
4-nitroaniline (5j)
(d, J = 7.8 Hz, 2 H, Ar), 7.17 (t, J = 7.8 Hz, 1 H, Ar),
3
7.30-7.35 (m, 6 H, Ar), 7.49 (d, J = 8.0 Hz, 1 H, Ar), 7.62
(t, 3J = 7.8 Hz, 2 H, Ar), and 8.05 (d, 3J = 8.0 Hz, 1 H, Ar).
13C-NMR (125.7 MHz, CDCl3): δC = 122.5 (2 CH), 125.1
(CH), 126.2 (2 CH), 127.4 (C), 128.7 (C), 129.2 (2 CH),
130.0 (2 CH), 132.5 (2 CH), 135.7 (2 CH), 139.1 (C), 144.9
(C), 147.0 (C), 154.9 (C=N), and 159.6 (C=N). MS: m/z
(%) = 407 (M+, 4), 329 (14), 252 (35), 154 (100), and
77 (54). Anal. Calc. for C20H14BrN3S: C, 58.83; H, 3.46;
and N, 10.29; Found: C, 58.85; H, 3.49; and N, 10.31.
Pale yellow powder; yield: 0.31 g (77%); mp: 199–203ꢀC.
IR (KBr) (νmax, cm−1): 3245, 1,680, 1,650, 1,533, 1,300,
1
and 1,230. H-NMR (500 MHz, CDCl3): δH = 3.64 (s, 3 H,
OMe), 6.03 (s, 1 H, NH), 7.29-7.34 (m, 5 H, Ar), 7.47-7.49
3
(m, 5 H, Ar), 7.60 (t, J = 7.8 Hz, 1 H, Ar), and 7.96 (d,
3J = 8.0 Hz, 1 H, Ar). 13C-NMR (125.7 MHz, CDCl3):
δC = 52.9 (OMe), 122.5 (C), 128.8 (2 CH), 129.2 (2 CH),
129.3 (CH), 129.4 (2 CH), 132.3 (CH), 132.5 (2 CH), 133.3
(CH), 134.4 (2 CH), 138.6 (C), 140.9 (C), 142.0 (C), 152.7
(C), 156.8 (C=N), and 164.7 (C=N). MS: m/z (%) = 404
(M+, 4), 327 (21), 282 (29), 122 (43), 107 (100), and
77 (87). Anal. Calc. for C21H16N4O3S: C, 62.36; H, 3.99;
and N, 13.85; Found: C, 62.38; H, 3.94; and N, 13.80.
3.9 | N-(6-Bromo-4-(phenylimino)-1H-benzo
[d][1,3]thiazine-2(4H)-ylidene)-
4-nitroaniline (5h)
Pale yellow powder; yield: 0.39 g (87%); mp: 199–201ꢀC.
IR (KBr) (νmax, cm−1): 3300, 1,671, 1,622, 1,541, 1,342,

DASTJERDI ET AL.
5
[8] H. Matsuoka, N. Ohi, M. Mihara, H. Suzuki, K. Miyamoto,
N. Maruyama, K. Tsuji, N. Kato, T. Akimoto, Y. Takeda, J. Med.
Chem. 1997, 40, 105.
[9] A. Alizadeh, Z. Noaparast, H. Sabahnoo, N. Zohreh, Synlett 2010,
2010, 1469.
[10] I. Yavari, M. Nematpour, T. Damghani, Mol. Divers. 2013, 17, 801.
[11] R. R. SCHMIDT, Synthesis 1972, 1972, 333.
[12] V. N. Yuskovets, B. A. Ivin, Tetrahedron Lett. 2003, 44, 5279.
[13] M. Koketsu, K. Tanaka, Y. Takenaka, C. D. Kwong, H. Ishihara,
Eur. J. Pharm. Sci. 2002, 15, 307.
4 | CONCLUSIONS
In conclusion, one-pot Cu-catalyzed synthesis of various
benzo [1,3] thiazine derivatives using the intramolecular C-
H activation reaction of isocyanides, heterocumulenes (car-
bon disulfide or isothiocyanate), and aniline derivatives in
acetonitrile at room temperature is reported. Finally, readily
available starting materials and catalysts, simplicity of the
purification procedure with good yields are the main advan-
tages of this methodology.
[14] I. Yavari, M. Nematpour, Z. Hossaini, Monatsh. Chem. 2010,
141, 229.
[15] F. Kakiuchi, N. Chatani, Adv. Synth. Catal. 2003, 345, 1077.
[16] V. Ritleng, C. Sirlin, M. Pfeffer, Chem. Rev. 2002, 102, 1731.
[17] D. Yang, B. An, W. Wei, L. Tian, B. Huang, H. Wang, ACS
Comb. Sci. 2015, 17, 113.
[18] B. Song, B. Xu, Chem. Soc. Rev. 2017, 46, 1103.
[19] D. Alberico, M. E. Scott, M. Lautens, Chem. Rev. 2007, 107, 174.
[20] M. Nematpour, E. Rezaee, S. A. Tabatabai, M. Jahani, Synlett
2017, 28, 1441.
ACKNOWLEDGMENTS
This work was supported by the National Institute for
Medical Research Development (NIMAD, project No.
962440).
[21] M. Nematpour, E. Rezaee, M. Jahani, S. A. Tabatabai, Tetrahe-
dron Lett. 2018, 59, 2054.
[22] M. Nematpour, E. Rezaee, M. Jahani, S. A. Tabatabai, Ultrason.
Sonochem. 2019, 50, 1.
ORCID
Sayyed A. Tabatabai https://orcid.org/0000-0002-7363-
3517
SUPPORTING INFORMATION
REFERENCES
Additional supporting information may be found online in
the Supporting Information section at the end of this article.
[1] A. Nagaraj, C. S. Reddy, J. Iran. Chem. Soc. 2008, 5, 262.
[2] T. E.-S. Ali, A. M. El-Kazak, Eur. J. Chem. 2010, 1, 6.
[3] M. R. Gannarapu, S. B. Vasamsetti, N. Punna, N. K. Royya,
S. R. Pamulaparthy, J. B. Nanubolu, S. Kotamraju, N. Banda,
Eur. J. Chem. 2014, 75, 143.
[4] V. Cecchetti, F. Schiaffella, O. Tabarrini, A. Fravolini, Bioorg.
Med. Chem. Lett. 2000, 10, 465.
[5] P. B. Raghuwanshi, A. Doshi, Asian J. Chem. 1994, 6, 291.
[6] V. Cecchetti, A. Fravolini, F. Schiaffella, O. Tabarrini, W. Zhou,
P. G. Pagella, J. Heterocyclic Chem. 1992, 29, 375.
How to cite this article: Dastjerdi HF,
Nematpour M, Rezaee E, Jahani M, Tabatabai SA.
One-pot synthesis of highly functionalized benzo
[1,3] thiazine from isocyanides, aniline, and
heterocumulene via Cu-catalyzed intramolecular C-H
activation reactions. J Chin Chem Soc. 2019;1–5.
https://doi.org/10.1002/jccs.201800493
[7] A. Macchiarulo, G. Costantino, D. Fringuelli, A. Vecchiarelli,
F. Schiaffella, R. Fringuelli, Bioorg. Med. Chem. 2002, 10, 3415.