Cu(i) catalysed annulation of isothiocyanates/isocyanates with 2-iodo-sulfonamides: Synthesis of benzodithiazines, benzothiadiazinones, benzothiazinylidene-anilines and benzothiazolylidene-anilines

Article abstract of DOI:10.1039/c9ob00994a

An efficient Cu(i)-catalysed cyclisation reaction of 2-iodobenzene sulfonamides with aryl-isothiocyanates and isocyanates that affords functionalised benzodithiazines and benzothiadiazinones, respectively, has been developed. Thus, in the reaction with ar

Full text of DOI:10.1039/c9ob00994a

View Article Online
View Journal
Organic &
Biomolecular
Chemistry
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: K. C. Kumara
Swamy, S. Kondipati and A. Siva Reddy, Org. Biomol. Chem., 2019, DOI: 10.1039/C9OB00994A.
Volume 15
Number 47
21 December 2017
Pages 9945-10124
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Organic &
Biomolecular
Chemistry
Accepted Manuscripts are published online shortly after acceptance,
rsc.li/obc
before technical editing, formatting and proof reading. Using this free
service, authors can make their results available to the community, in
citable form, before we publish the edited article. We will replace this
Accepted Manuscript with the edited and formatted Advance Article as
soon as it is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes to the
text and/or graphics, which may alter content. The journal’s standard
Terms & Conditions and the Ethical guidelines still apply. In no event
ISSN 1477-0520
PAPER
I . J. Dmochowski et al.
Oligonucleotide modifi cations enhance probe stability for
shall the Royal Society of Chemistry be held responsible for any errors
single cell transcriptome in vivo analysis (TIVA)
or omissions in this Accepted Manuscript or any consequences arising
from the use of any information it contains.
rsc.li/obc

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 1 of 14
View Article Online
DOI: 10.1039/C9OB00994A
Journal Name
ARTICLE
Cu(I) catalysed annulation of isothiocyanates/ isocyanates with 2-
iodo-sulfonamides:
Synthesis
of
benzodithiazines,
and
benzothiadiazinones,
benzothiazolylidene-anilines
benzothiazinylidene-anilines
Received 00th January 20xx,
Accepted 00th January 20xx
K. Sandeep,a Alla Siva Reddy b and K. C. Kumara Swamy*a
DOI: 10.1039/x0xx00000x
An efficient Cu(I)-catalysed cyclisation reaction of 2-iodobenzene sulfonamides with aryl-isothiocyanates and isocyanates
that affords functionalised benzodithiazines and benzothiadiazinones, respectively, has been developed. Thus, in the
reaction with aryl isothiocyanate (Ar-N=C=S), the C=S moiety participates in the cyclisation leading to a dithiazine. By
contrast, in the case of aryl isocyanate (Ar-N=C=O), the N=C part is involved in the cyclisation and a thiadiazinone is
obtained. Analogous reactions of isothiocyanates with N-tosyl-2-iodo-anilines and 2-iodo-benzyl sulfonamides afford
(benzothiazin-2-ylidene)anilines and (benzothiazol-2-ylidene)anilines, respectively. Probable mechanistic pathways are
briefly discussed.
www.rsc.org/
reported
a cascade synthesis of 1,3-benzothiazoles using 2-
haloarylisothiocyanates (Scheme 1f).23 Our group synthesised
benzosultams through copper catalysis that entails the use of
elemental sulfur and selenium (Scheme 1g).24 An important review
on [Cu]-catalysed domino reactions by Xi and coworkers has
appeared in the year 2014.25
Introduction
The sulfonamide moiety is a robust constituent of numerous
pharmaceutical molecules.1,2 Sulfonamides have drawn enormous
attention in exploring new synthetic methodologies for
peptidomimetics that represent a broad array of sulfa-antibiotics.3-5
Recent trends show that their cyclic counterparts (sultams) have
gained prominence in medicinal chemistry.6-8 Compounds affluent
with benzosultam core manifest diverse biological activities like
O
O
O
O
O
O
S
Me
S
O
O
S
Et
O
O
S
N
OMe
H
O
H
H2N
S
N
N
N
O
H
Me
O
O
antimalarial,9 anti-inflammatory (e.g., Ampiroxicam, Calpain
I
HN
Et
Brinzolamide
carbonic anhydrase inhibitor
OCO2Et
Ampiroxicam
inhibitor),10 and enzyme inhibition (e.g., brinzolamide,
trichloromethiazide) (Fig. 1). In addition to these, fused
Calpain I inhibitor
COX II inhibitor
benzosultams can be used as protecting groups, chiral auxiliaries,
Cl
H
12
and directed metallation groups (DMGs).11,
Among the fused
Cl
S
S
Cl
S
S
N
N
N
Cl
Cl
benzosultams, benzodithiazine-1,1-dioxide shows inhibitory
N
N
HN
Me
S
SO2NH2
properties against HIV,13-15 and hypoglycemia.16
O
O
O
O
Me
O
O
Me
Anti-HIV activity
II
I
Anti- HIV activity
Trichloromethiazide
(diuretic drug)
An important synthetic approach towards benzothiazine dioxides
involves intramolecular cyclisation of terminal alkenes as reported
by Che et al. (Scheme 1a).17 Murakami et al. demonstrated the
reaction between benzothiatriazine and allenes under [Ni] catalysis
that involves dinitrogen elimination (Scheme 1b).18 Mondal and co-
workers reported a method utilizing Sonogashira coupling of
alkynes to 2-bromobenzene sulfonamides (Scheme 1c).19 Cramer’s
group reported Rh(III)-catalysed synthesis of sultams via C-H
activation, directed by acyl group tethered to nitrogen (Scheme
1d).20 The groups of Rao and Volla independently obtained sultam
scaffolds by reacting allenes with aryl sulfonamides (Scheme 1d)
using cobalt catalysis and by employing C-H activation.21 Guo‘s
Figure 1. Selected pharmacologically active benzosultams.
In addition to those shown in Scheme 1, use of heterocumulenes is
known to generate many useful heterocycles that are relevant to
our present study. Thus for the synthesis of pyrimido[1,2-
c][1,3]benzothiazin-6-imines, Ohno’s group utilized base catalysed
reaction
of
2-(2-haloaryl)tetrahydropyrimidines
with
heterocumulenes such as carbon disulfide, isothiocyanates and
isocyanates (Scheme 2a).26a While the research groups of Bao and
Wu have reported CuI catalysed synthesis of 2-aminobenzothiazoles
by treating 2-iodo-anilines with isothiocyanates,26b-c Li as well as
Ding have shown that similar reaction can be accomplished by using
FeF3 or FeCl3 (Scheme 2b).26d-f Interesting modifications using
Merrifeld resin or simply base mediated synthesis have also been
subsequently reported by the groups of L. Wang and R. Wang
respectively.26g-h Interestingly, in a later work, Zhang et al reported
a tandem reaction of 2-iodoanilines with isothiocyanates leading to
2-aminobenzothiazoles that utilised only 1,10-phenanthroline.26i
Even a combination of CS2 and amine/thiol can be utilized under
[Cu]-catalyzed conditions as shown by Ma’s group (Scheme 2c).27
group
reported
CuI-NPs
catalysed
from
synthesis
isothiocyanates
of
and
benzoimidazothiazineimines
benzimidazoles (Scheme 1e).22 Patel and coworkers have earlier
a. School of Chemistry, University of Hyderabad, Hyderabad 500 046, Telangana,
India. Tel: (+91)-40-231348560; E-mail: kckssc@uohyd.ac.in, kckssc@yahoo.com.
†Electronic Supplementary Information (ESI) available: [Crystal data and copies of
1H/13
C NMR spectra]. CCDC numbers are 1857227-1857231. See DOI:
10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 2 of 14
ARTICLE
Journal Name
Carbodiimides form another group of substrates that can be
utilized, as shown by Xi and co-workers (Scheme 2d).28a Use of an
N
X
N
Y
Y=C=Z
NaH
View Article Online
DOI: 10.1039/C9OB00994A
N
N
(a)
(b)
H
DMF/ 80 oC/ 12 h
ref. 26a
amide Instead of an amine can lead to
a six-membered
Z
dihydroquinazolin-4(1H)-ones (Scheme 2e).28b Li and coworkers
have also reported interesting cyclisation reactions of
isothiocyanates to obtain N,S-containing heterocycles.28c-e We have
Y, Z = S, NR, or O
X = Br, F
NCS
NH2
N
S
conditions
NH
been investigating the reactivity of sultam motifs and
R1
I
R
R
29-30
isothiocyanates/isocyanates,25,
and in this paper, we report
R1
conditions: (i) CuI/phen//K2CO3/DMSO/95 oC/ 24 h (ref. 26b)
(ii) CuI/phen/DABCO/toluene/50 oC/ 2-48 h (ref. 26c)
(iii) FeF3/phen/Et3N/DMSO/ 80 oC/2-4 h (refs. 26d-e)
access to functionalised benzosultams by copper-catalysed one pot
cyclisation of substituted sulfonamides (cf. Scheme 2f-g).
Specifically, we would like to highlight the following: (i) While the
C=S moiety forms a part of the sultam ring in the reaction with
isothiocyanates, the N=C moiety becomes a part of the sultam ring
in the case of isocyanates, reflecting the differing nucleophilicity of
the N, S and O centers. Although earlier reports have mentioned
the differences between isothiocyanates/isocyanates,31-33 our
method offers two types of cyclisation under the same conditions
yielding different type of products. (ii) The reaction can be extended
to 2-iodo-benzyl sulfonamides and N-tosyl-2-iodo-anilines leading
to six- and five-membered ring sultams.
(iv) FeCl3/phen/DABCO/PTC-4/H2O/80 oC/overnight (ref. 26f)
(v) Phen/NaHCO3/H2O/80 oC/ 2 h (ref. 26i)
N
S
NH2
N
S
conditions
SR1
or
NR1R2
CS2
(c)
R
I
R
R
conditions: (i) HNR1R2/CuCl2.H2O/K2CO3/DMF/110 oC/6 h (ref. 27a) or
(ii) HSR1/CuBr/K2CO3/DMF/110 oC/12 h (ref. 27b)
R1
N
NH2
N
CuI/NaOt-Bu/NMP
NHR2
(d)
(e)
C N
90-120 oC/24 h
ref. 28a
R2
N
R
I
R
R1
O
O
CuI/DMEDA
NH2
NH
O
O
O
O
NHR1
R1
ArNCS
S
S
N
Cs2CO3/toluene
120 oC/24 h
ref. 28b
[Au]
Br
N
S
R
R
(a)
(b)
ref. 17
Ar
Me
This work
O
O
O
O
O
O
N
S
R
S
Me
Me
Ac
S
Me
R
R
X = S
N
N
N
[Ni]
.
O
O
R1
ref. 18
S
N
N
S
I
R
Conditions
N
Ar
(f)
H
NCX
Ar-
O
O
O
O
R1
O
O
S
Me
S
N
S
R
N
[Pd]
X = O
R1
N
H
(c)
(d)
R1
ref. 19
Br
R1
N
O
Ts
Ar
Ts
N
O
O
O
O
O
O
Ts
[Rh]
NH
R
S
S
N
AQ
S
[Co]
R = Ac
N
N
N
H
Ts
H
R4
N
R2
R3
R2
R4
R3
I
R3
R1
(g)
R
NCS
R1
I
R1
Ar-
N
.
R2 R3
R2
S
N
Conditions
S
Conditions
Ar
ref. 20
ref. 21 (a)
Ar
AQ = 8-aminoquinolinyl
Conditions: CuI/ K2CO3, 1,10-phenanthroline, THF, 80 o
C
N
N
CuI NPs
ref. 22
(e)
(f)
Ar-NCS
N
Scheme 2 Selected reactions of cumulenes and the present work.
N
R1
R1
S
N
Ar
H
X
X = Br, I
Results and Discussion
NCS
CuI/ 1,10-phen
N
PhSH
SPh
S
+
K2CO3
ref. 23
I
The sulfonamide precursors 1a-j used for the present study
were prepared by following literature procedures;32,
these
34
O
O
O
O
X (3 equiv)
precursors are shown in Figure 2 along with the isothiocyanates 2a-
o. In the case of iodination of naphthalene sulfonamide, we
S
I
R
S
R
N
CuI / K2CO3
N
(g)
H
R1
R1
H2O (1.5 equiv)
ref. 24
X
observed
methylnaphthalene-2-sulfonamide
a
3:1 isomeric mixture, most likely of 1-iodo-N-
(1f) and 3-iodo-N-
R2
R2
X = S or Se
methylnaphthalene-2-sulfonamide that was used as such. Our
preliminary exploration commenced by choosing the reaction
between 1a and 2a as model substrates for the identification of
controlling factors such as catalyst, solvent, base and ligand as
presented in Table 1. To begin with, we used 5 mol% copper(I)
iodide as the catalyst in 1,4-dioxane as the solvent at 80 oC and
obtained the desired dihydrobenzo[1,4,2]dithiazine-1,1-dioxide 3aa
in 43% yield (Table 1, entry 1). Use of toluene improved the yield to
68% (entry 2). Solvents like CH3CN, DCE, PEG-400, DMF (entries 3-6)
were ineffective. The best result of 92% yield was achieved when
THF was used as the solvent (entry 7). Copper catalysts like CuO,
CuBr2, CuBr, CuCl, Cu(OAc)2, Cu(OTf)2, and Cu(OPiv)2 were
separately examined and were found to be less effective (entries
8−14). Thus CuI (entry 7) turned out to be the best choice. Other
workers also have observed that CuI in general works better than
Scheme 1 Selected synthetic strategies for benzosultams.
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 3 of 14
Organic & Biomolecular Chemistry
Please do not adjust margins
Journal Name
ARTICLE
CuBr,35 although there are exceptions.36 No product was identified
in the absence of the catalyst (entry 15). Bases, such as KOtBu,
Na2CO3, Cs2CO3, K3PO4, reduced the yield of the product (entries 16-
19). Ligands such as pyridine, PPh3, Et3N, and TMEDA (entries
20−23) proved ineffective in promoting the reaction. In the absence
of ligand or base, low yields or traces of the product were observed
(entries 24-25). Lowering of catalyst loading to 2.5 mol% also
decreased the yield (entry 26). Considering the reaction time, the
best result for this reaction is by using copper(I) iodide in THF at 80
°C/ 12 h (Table 1, entry 7). The structure of 3aa was confirmed by
1H/ 13C NMR, mass spectrometry and single crystal X-ray diffraction
[Fig. 3 (left)].
5
6
7
8
CuI
CuI
PEG-
400
DMF
K2CO3
K2CO3
K2CO3
K2CO3
1,10-
32
View Article Online
pDhOenI:a1n0t.1h0r3o9l/inCe9OB00994A
1,10-
phenanthroline
1,10-
phenanthroline
1,10-
25
92
CuI
THF
CuO
THF
trace
phenanthroline
9
CuBr2
CuBr
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
KOtBu
Na2CO3
Cs2CO3
1,10-
phenanthroline
1,10-
phenanthroline
1,10-
phenanthroline
1,10-
phenanthroline
1,10-
phenanthroline
1,10-
phenanthroline
1,10-
phenanthroline
1,10-
phenanthroline
1,10-
phenanthroline
1,10-
phenanthroline
1,10-
phenanthroline
Pyridine
PPh3
trace
trace
trace
15
10
11
12
13
14
15
16
17
18
CuCl
Isothiocyanates
Iodo-sulfonamides
O
O
R2-NCS
R
S
Cu(OAc)2
Cu(OTf)2
Cu(OPiv)2
-
N
R2 = Ph
2a
( )
H
R1
X
2b
)
4-MeO-C6H4
4-F3C-C6H4
3-Cl-C6H4
cyc-C6H11
4-O2N-C6H4
4-NC-C6H4
4-Cl-C6H4
4-Me-C6H4
2,4,6-Me3C6H2
CH2=CH-CH2
iPr
(
35
2c
(
)
R = Me, R1 = Me, X = I
R = Me, R1 = OMe, X = I
R = Me, R1 = tBu, X = I
R = Me, R1 = Ph,
R = Bn, R1 = Me, X = I
R = Me, R1 = H
R = Me, R1 = F,
R = Me, R1 = H,
R = Me, R' = H,
(1a)
(1b)
(1c)
(1d)
(1e)
(1g)
(1h)
(1i)
2d
(
)
25
2e
(
)
2f
(
(
(
)
X = I
2g
)
NR
2h
)
X = I
X = I
2i
(
)
CuI
43
2j
(
)
X = Br
2k
(
)
1j
X = Cl (
)
CuI
58
2l
(
)
Me
2m
( )
n-Bu
HN
I
2n
)
(2o)
3,5-CF3-C6H3
Et
(
S
O
CuI
47
(1f)
O
(Major isomer;
see text)
19
CuI
THF
K3PO4
62
Figure 2 Sulfonamide and isothiocyanate precursors used in this study.
20
21
22
23
24
25
CuI
CuI
CuI
CuI
CuI
CuI
THF
THF
THF
THF
THF
THF
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
-
25
37
25
trace
23
Et3N
TMEDA
-
1,10-
phenanthroline
1,10-
trace
c
26
CuId
THF
K2CO3
29
phenanthroline
Figure 3 ORTEP (ellipsoid contour probability 50%) of compound 3aa (CCDC
no. 1857227). Selected bond lengths [Å] with esds in parentheses: C(6)-S(2)
1.7648(17), N(1)-C(7) 1.403(2), C(7)-S(2) 1.7815(17), N(2)-C(7) 1.258(2)..
aReaction conditions: amide (0.3 mmol), isothiocyanate (0.36 mmol),
catalyst (5 mol %), ligand (10 mol %), base (0.6 mmol), solvent (2 mL), 80 oC
(oil bath). bIsolated yields. cReaction was performed at 100 oC (oil bath) for 2
d. d2.5 mol% catalyst was used. 1,10-phen.=1,10-phenanthroline.
Table 1 Optimisation study of [Cu]-catalysed reaction between 1a
and 2aa
Gratifyingly, the above reaction proceeded smoothly with iodo-
O
O
S
Me
NCS
O
O
[Cu]-catalyst
ligand
sulfonamides
1a-j
with
the
respective
N
S
I
Me
N
dihydrobenzo[1,4,2]dithiazine-1,1-dioxides 3aa-3hi being obtained
in good to excellent yields (Scheme 3). The reaction is compatible
with electron neutral (Ph), electron rich (4-OMe) and electron
deficient (4-CF3, 3-Cl) isothiocyanates with sulfonamide 1a affording
the sultams (3aa-3ae) in 77-92% yields. The reaction of methoxy-
substituted sulfonamide 1b with isothiocyanate proceeded
smoothly to generate the anticipated products (3bb-3bm) in
excellent yields. Not only aromatic but alicyclic (3be) and aliphatic
(3bk, 3bm) isothiocyanates underwent reaction making this
strategy viable to a range of substrates. Annulated products 3ca-
3ch were obtained in good to excellent yields 80-88% (Scheme 3),
using sulfonamide 1c bearing tert-butyl substituent at para position.
Structure of 3cc was also confirmed by X-ray analysis [cf. Fig. 4, left].
Excellent yields of 3dc, 3di, and 3dl (77-89%) were obtained using
biphenyl sulfonamide (1d). Subsequently, N-benzyl-substituted
H
Me
S
N
base, solvent
80 oC, 12 h
Me
3aa
1a
2a
ent
ry
[Cu]
(5 mol%)
solvent
base
ligand
yield
[%]b
1
2
3
4
CuI
dioxane
toluene
CH3CN
DCE
K2CO3
K2CO3
K2CO3
K2CO3
1,10-
phenanthroline
1,10-
phenanthroline
1,10-
phenanthroline
1,10-
43
68
CuI
CuI
CuI
28
trace
phenanthroline
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 4 of 14
ARTICLE
Journal Name
R2
sulfonamide (1e) was also employed as the substrate, and the
desired sultams 3ea and 3ef-3eg were obtained with yields ranging
from 76-86%. It may be noted that only one isomer with aryl group
at C=N moiety cis to the ring sulfur is formed, most likely to avoid
steric interactions with the NR group of the six-membered ring. In
the case of 1-iodo-naphthalene-2-sulfonamide (1f), two isomers
were detected (Scheme 3, 3fa-3fd) due to the possibility of
iodination on both sides of naphthalene sulfonamide. We were able
to identify the minor isomeric product (3fb’) in one case by single
crystal X-ray crystallography [cf. Fig. 4, right].37 Electron-neutral as
well as electron-withdrawing group containing sulfonamides (1g-h)
also afforded the products 3gi-3hi in good yields. This methodology
also yields the desired sultam 3gi in 80% yield when bromine (cf. 1i),
instead of iodine, is present at the ortho position; the chloro
precursor 1j did not react. Interestingly, the newly introduced sulfur
in 3ch is resistant to oxidation by m-CPBA (mp, tlc, 1H NMR
evidence).
N
View Article Online
Me
O
2
HN
S
2a-f
R -NCS (
)
I
O
O
DOI: 10.1039/CS9OB0M0e994A
O
O
N
S
S
R
CuI (5 mol %)
S
I
R
or
N
or
N
O
H
O
K2CO3 (2 equiv)
1,10-phenanthroline
R1
O
S
N
R2
R1
O
THF, 80 o
C
1a-i
3
O
O
O
O
O
O
O
S
S
Me
S
S
Me
N
S
S
Me
S
Me
N
N
N
N
N
Me
N
Me
Me
N
Me
S
3ab
3ac (77%)
3ad (84%)
(83%)
3aa
(92%)
Cl
(X-ray)
CF3
Me
OMe
O
O
O
O
O
O
O
S
O
S
Me
S
S
S
S
Me
N
Me
N
N
N
N
N
MeO
Cl
S
N
MeO
3bd
N
Me
MeO
3ba
S
3ae
(86%)
3be
(80%)
O
(77%)
(72%)
O
O
O
O
S
O
O
O
S
S
Me
S
S
Me
Me
S
Me
N
N
N
N
MeO
N
MeO
N
MeO
S
N
MeO
S
N
3bg
(86%)
3bi
3bh
(74%)
O
3bf
(85%)
O
(78%)
Cl
Me
NO2
Me
N
CN
O
O
O
O
O
O
S
Me
S
Me
S
S
Me
S
S
N
N
N
N
MeO
S
N
MeO
iPr
S
N
MeO
Me
N
MeO
Me
3bk
3bj
(62%)
3bl (80%)
3bm (64%)
(74%)
Me
Me
O
O
O
S
O
O
O
O
O
S
S
Me
Me
N
S
Me
N
N
S
S
Me
N
N
N
N
tBu
S
tBu
S
tBu
N
3dc
(79%)
3ca
3cc
(80%)
(88%)
3ch
(85%)
(X-ray)
CF3
Bn
N
Figure 4 ORTEPs (ellipsoid contour probability 50%) for compounds 3cc (left,
CCDC no. 1857231) and 3fb’ (right, CCDC no. 1857229). Selected bond
lengths [Å] with esds in parentheses: 3cc S(2)-C(6) 1.7649(15), S(2)-C(7)
1.7772(16), C(7)-N(2) 1.257(2), C(7)-N(1) 1.398(19). 3fb’ N(1)-C(11) 1.419(5),
N(2)-C(11) 1.260(5), S(2)-C(5) 1.750(5), S(2)-C(11) 1.776(4).
CF3
Cl
O
O
O
O
N
O
O
O
O
S
S
S
Me
N
S
S
Me
N
S
S
Bn
N
N
N
Me
N
S
Me
iPr
3dl
3di
(77%)
3ef
(80%)
(89%)
O
3ea
(86%)
MeO
NO2
Me
O
Cl
S
Bn
The versatility of the optimised Cu(I) catalysed annulation
strategy for sultam analogues was not limited to isothiocyanates.
Indeed this protocol could be successfully extended to isocyanates.
To test this, we performed the reaction between iodo-sulfonamide
1a and phenyl isocyanate 4a. The reaction proceeded smoothly
giving the desired product 5aa in 88% yield, but with a switch in
cyclisation mode which involves nitrogen, rather than an oxygen
atom, as a part of the ring. An interesting feature of this protocol is
the formation of a cyclic urea analogue. Substituents on aryl
isocyanates were well tolerated under the standard reaction
conditions (cf. 5ab-5dd; Scheme 4). Electron-rich aryl isocyanates
sustained well, furnishing the desired products (e.g., 5ab, 5bb, 5gb-
5hb) in good yields. Utilizing aryl isocyanates with substituents such
as -Cl, -F, and -Br also, the desired products (cf. 5ac-5ae) were
obtained in high yields. Sulfonamides 1b-d and 1g-1h also gave
decent yields with different isocyanates under these conditions (79-
92%, 5bb-5dd, 5gb-5hb). The solid state structure of product 5ad is
shown in Fig. 5.
N
N
S
N
N
Me
O
Me
Me
O
Me
S
N
N
S
S
N
S
N
O
S
S
O
O
O
CN
major isomer (see text)
3fb
3eg
(76%)
3fa
(90%)
3fd
(84%)
O
(88%)
O
O
O
N
O
O
S
S
S
S
S
Me
Me
N
Me
N
F
N
N
S
N
3hi
(80%)
3gi
3fb'
X-ray
1g
1i
85% using
80% using
CH3
CH3
OMe
Scheme
3 Substrate scope for [Cu]-catalysed annulation reaction of
substituted iodo-sulfonamides with isothiocyanates.
Figure 5 ORTEP (ellipsoid contour probability 50%) for compound 5ad (CCDC
no. 1857230). Selected bond lengths [Å] with esds in parentheses: N(2)-C(6)
1.390(9), N(1)-C(13) 1.398(11), N(2)-C(7) 1.474(10), O(3)-C(13) 1.237(11).
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 5 of 14
Organic & Biomolecular Chemistry
Please do not adjust margins
Journal Name
ARTICLE
We then applied the above annulation approach to 2-iodo-N-
View Article Online
tosyl system and to our delight, obtained benzo[d]thiazol-2(3H)-
DOI: 10.1039/C9OB00994A
O
O
NCO
R
CuI (5 mol %)
ylidene-anilines in good to excellent yields. We then checked the
substrate scope. As illustrated in Scheme 6, all the reactions tested
worked smoothly and the annulation products (9a-9k) were
obtained in moderate to good yields (up to 79%). Aryl
isothiocyanates bearing electron-donating (Me, isopropyl; cf. 9d-9e)
as well as electron withdrawing (CF3, Cl) (9b-c, 9f) substituents
showed good compatibility. An alkyl isothiocyanate also worked
well (e.g., 9g). Electron donating (methyl) group on sulfonamides
also worked well to yield annulated products (9h-9i) in god yield.
Even heterocyclic sulfonyl moiety in place of tosyl furnished the
desired products (9j-9k) in good yields. Reaction using isocyanates,
though, did not work. The structure of 9b was further confirmed by
single crystal X-ray analysis [cf. Figure 6].We believe that this
approach is better than the previous routes both in terms of cost
and the number of steps involved in the synthesis of
thiazolylidenes.38
S
N
Me
O
N
K2CO3 (2 equiv)
1a-d or 1f
R1
1,10-phenanthroline
THF, 80 o
C
4a
4b
)
R = H ( ), Me (
4c
4d
)
Cl ( ), F (
4e
5
Br (
)
R
O
O
O
O
O
O
O
O
S
N
Me
O
S
N
Me
O
S
N
Me
O
S
N
Me
O
N
N
N
N
Me
Me
Me
5ab
Me
5aa
(88%)
5ad
(82%)
(86%)
(X-ray)
5ac
(78%)
F
S
N
Me
Cl
O
O
O
O
O
O
O
O
S
N
Me
O
S
N
Me
O
Me
O
S
Me
O
N
N
N
N
Ph
Me
tBu
N
MeO
5dd
(87%)
5cc
(85%)
5bb
(92%)
5ae
(73%)
F
R1
S
R1
S
Cl
Br
Me
NCS
O
O
CuI (5 mol %)
O
O
O
O
O
O
N
S
N
Me
S
N
Me
O
K2CO3 (2 equiv)
N
NH
N
N
1,10-phenanthroline
S
O
F
R
R
R
I
THF, 80 o
C
: R = H, R1 = p-tolyl
9
2
8a
R
: R = Me, R1 = p-tolyl
: R = H, R1 = 2-thiophenyl
8b
8c
5gb
(87%)
5hb
(79%)
Me
Me
Me
Me
Me
Me
Scheme
4 Substrate scope for [Cu]-catalysed annulation Reaction of
substituted iodo-sulfonamides with phenyl Isocyanates.
O
O
O
N
O
N
O
O
S
N
O
N
S
N
S
N
O
N
S
N
S
S
We have also been able to demonstrate the synthetic potential of
the above annulation strategy to 2-iodo-benzyl systems to furnish
(benzo[1,3]thiazin-2-ylidene)anilines under the above conditions
(Scheme 5). The major difference is that unlike in the previous
approach, the sulfonyl moiety tethered to the nitrogen exists
outside the ring. Both electron-donating groups (Me; 7f-7g) and -
withdrawing groups (Cl, CF3; 7c-7d) furnished the corresponding
products in excellent yields in 70-81%. The reaction did not work
with isocyanates, but worked well with aliphatic isothioyanates (cf.
7e, 7h).
S
S
Cl
9d
(78%)
9a
9b
(X-ray)
9c
(77%)
(77%)
(75%)
CF3
Me
Me
Me
Me
Me
O
S
O
N
O
O
N
O
S
N
O
N
O
O
S
N
S
N
N
S
Me
N
iPr
S
S
S
CH3
CF3
9h
(62%)
9f (61%)
9g (79%)
(using EtNCS)
CF3
9e (65%)
F3C
Me
S
S
O
O
NCS
O
O
O
O
S
O
N
S O
CuI (5 mol %)
K2CO3 (2 equiv)
S
O
N
S
N
S
N
N
N
N
N
O
H
N
S
Me
S
1,10-phenanthroline
THF, 80 oC, 12h
S
S
I
R
Cl
9k
Cl
(62%)
9i
9j
(74%)
(66%)
R
2
6
7
Scheme 6 Substrate scope for [Cu]-catalysed annulation reaction of n-(2-
iodophenyl)-4-methylbenzene sulfonamide with isothiocyanates.
O
O
O
O
S
S
S
S
N
N
N
N
O
O
O
O
S
N
S
N
S
N
S
N
7c
(70%)
7a
7b
7d
(71%)
(80%)
(81%)
Cl
O
OMe
CF3
O
O
S
O
O
S
S
S
N
N
N
N
N
O
O
O
S
N
S
N
S
N
S
Figure 6 ORTEP (ellipsoid contour probability 50%) for compound 9b (CCDC
no. 1857228). Selected bond lengths [Å] with esds in parentheses: S(2)-C(12)
1.749(2), S(2)-C(13) 1.759(2), C(13)-N(2) 1.262(3), C(13)-N(1) 1.408(3).
Me
Me
CH3
7e
(76%)
7h
(81%)
7f
(74%)
7g
(76%)
(using EtNCS)
Me
Me
Scheme 5 Substrate scope for [Cu]-catalysed annulation reaction of n-(2-
iodobenzyl)benzene sulfonamide with isothiocyanates.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 6 of 14
ARTICLE
Journal Name
O
O
A
working hypothesis to account for the formation of
View Article Online
DOI: 10.1039/C9OB00994A
S
Me
N
functionalised benzodithiazines (3) and benzothiadiazinones (5) is
depicted in Scheme 7. The catalytic cycle commences with the
abstraction of proton by the base, generating the nitrogen-centered
anion A. This is consistent with the observation that the compound
4-Me-C6H4SO2NHMe reacted readily with 4-iodoanisole under our
conditions to form 4-Me-C6H4SO2N(Me)C6H4-OMe (1H NMR,
HRMS),39 suggesting that the NH moiety can undergo
deprotonation leading to the anion under the conditions employed
(Scheme 8a); however, the reaction of 2-iodo-4-MeO-
C6H4SO2NHMe with iodo-anisole was very sluggish (tlc; Scheme 8b)
probably due to steric factors. We also treated (p-tolyl)SO2NHMe,
which is devoid of iodine at the ortho-position, with p-
tolylisothiocyanate under our reaction conditions, assuming that
the reaction stops at thioamide (Scheme 8c). Although the reaction
mixture showed that much of (p-tolyl)SO2NHMe was consumed
(tlc), we could not identify any intermediate clearly. On the basis of
these data, we think that species A may attack the carbon of
isothiocyanate 2 and then CuI is inserted with concomitant
generation of active Cu(III) intermediate C. The reaction of aryl
iodides with ligated CuI to form Cu(III) species been proposed
earlier by others.40 As mentioned by Ma and co-workers, details of
the reaction are highly dependent on the type of bidentate neutral
ligand used, but the oxidation state of copper may shuttle between
I and III.40a Subsequent attack of sulfur anion onto copper leads to
the seven-membered cyclic species which upon reductive
elimination gives the sultam 3 and regenerates CuI to finish the
catalytic cycle. In an analogous manner, the isocyanates 4 react
with the iodosulfonamides to give the intermediate B. The main
difference, however, is that the negative charge in this case resides
on the more nucleophilic nitrogen. Subsequently, the nitrogen
inserted sultam 5. Formation of products 7 and 9 may be
rationalised in a manner similar to that for 3. As an alternative, it is
also possible to have intermediates of type D-G in our reaction;
binding of amidic nitrogen to copper has been suggested
elsewhere.40c-d In the absence of any substantial evidence in favour
of either pathway, we limit our discussion on the mechanism here.
H
Me
I
1
K2CO3
-H+
O
Ar
Ar
O
N=C=S
2
N=C=O
4
S
Me
N
CuI
CuI
Me
I
1, 10-phenanthroline
1, 10-phenanthroline
A
O
O
Me
O
O
S
Me
S
N
O
N
N
N
Ar
Me
S
[Cu]
I
Ar
Me
[Cu]
I
I
I
B
C
Reductive
Elimination
-CuI, -I-
-CuI, -I-
O
Reductive
Elimination
O
O
O
S
S
Me
Me
N
N
Me
S
N
Me
N
O
Ar
Ar
5
3
Me
S
O
S
O
O
O
Ar
Me
N
O
O
O
S
Me
N
O
N
S
Me
S
N
N
O
[Cu]
Me
I
Me
N
[Cu]
I
Me
[Cu]
Me
[Cu]
I
Ar
E
F
G
D
I
Scheme 7 Plausible pathways for the formation of 3 and 5; also shown at
the bottom are other possible intermediates.
O
O
I
O
S
Me
O
CuI (5 mol %)
K2CO3 (2 equiv)
N
S
Me
N
(a)
(b)
H
Me
1,10-phenanthroline
THF, 80 oC, 12 h
Me
OMe
I
OMe
O
O
CuI (5 mol %)
K2CO3 (2 equiv)
S
Me
Me
N
Too sluggish
(No Reaction)
H
1,10-phenanthroline
THF, 80 oC, 12 h
MeO
I
OMe
NCS
O
O
S
S
Me
NH
O
O
N
CuI (5 mol %)
K2CO3 (2 equiv)
S
N
(c)
Me
H
1,10-phenanthroline
THF, 80 oC, 12 h
Me
Me
Not detected
Me
Scheme 8 Control experiments to check the reaction pathways.
Conclusions
We have developed an efficient [Cu]-catalysed synthetic
protocol
for
the
construction
Although
of
the
benzodithiazines/benzothiadiazinones.
nucleophilicities of oxygen and sulfur in isocyanates/
isothiocyanates can be expected to be different, manifestation of
this difference has not been clearly demonstrated before; in the
present work, we have shown that this feature gives rise to vastly
different cyclisation products. The practicality of this method is
exemplified by the use of inexpensive copper catalyst, ample
substrate scope, excellent stereoselectivity, and good functional
group tolerance. This methodology is elaborated further for the
facile
construction
of
(benzothiazinylidene)anilines
and
(benzothiazolylidene)anilines. It may be noted that allenes and
6 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 7 of 14
Organic & Biomolecular Chemistry
Please do not adjust margins
Journal Name
ARTICLE
o
keteniminium species (resonance forms of ynamides) have a central monitored by TLC. After cooling to rt (25 C), the reaction mixture
View Article Online
sp-hybridized carbon that is susceptible for attack from a species was filtered through celite, the solvent was removed under
DOI: 10.1039/C9OB00994A
like A shown in Scheme 6 and hence may be useful substrates vacuum, and the crude product was purified by column
under appropriate conditions.
chromatography by using silica gel with ethyl acetate/hexane (5:95)
mixture as the eluent to afford the corresponding sultam. Details on
optimisation studies are given in Table 1. All the products were
isolated in essentially the same manner.
Experimental
General Information
(Z)-2,6-Dimethyl-3-(phenylimino)-2,3-
Chemicals and solvents were purified when required according to
standard procedures.41 All reactions, unless stated otherwise, were
dihydrobenzo[e][1,4,2]dithiazine 1,1-dioxide (3aa). White solid,
Yield 0.088 g (92%). Mp 157-159 oC; Rf = 0.53 (95:5 hexane/ethyl
acetate); IR (neat) ν 3047, 2946, 1621, 1589, 1467, 1413, 1383,
1349, 1186, 1116, 1051, 904, 819, 772, 698, 680 cm-1; 1H NMR (500
MHz, CDCl3) δ (ppm) 7.88 (d, J = 8.0 Hz, 1H), 7.42-7.39 (m, 2H), 7.28-
7.25 (m, 1H), 7.22- 7.19 (m, 1H), 7.14 (s, 1H), 6.94 (d, J = 8.5 Hz, 2H),
3.53 (s, 3H), 2.40 (s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 147.0,
146.6, 144.3, 133.3, 129.7, 129.4, 128.5, 128.2, 124.8, 124.1, 121.0,
31.9, 21.6; HRMS (ESI) Calcd. for C15H15N2O2S2 (M++H): m/z
319.0569. Found: 319.0577. This compound was crystallised from
ethyl acetate/hexane (2:1) mixture at 25 oC. X-ray structure was
determined for this sample.
1
performed in a dry nitrogen atmosphere. H and 13C spectra were
recorded in CDCl3 (unless stated otherwise) with shifts referenced
to SiMe4 (δ = 0) Infrared spectra were recorded neat or by using KBr
pellets. Melting points were determined by using a local hot-stage
melting point apparatus and are uncorrected (not calibrated). For
TLC, glass microslides were coated with silica-gel-GF254 (mesh size
75 μ) and spots were identified using iodine or UV chamber as
appropriate. For column chromatography, silica gel of 100−200
mesh size was used. LC−MS or HRMS (ESI-TOF) equipment was used
to record mass spectra for isolated compounds where appropriate.
All the isothiocyanates (2a-2o) and isocyanates (4a-4e) were bought
from chemical vendors.
(Z)-3-((4-Methoxyphenyl)imino)-2,6-dimethyl-2,3-
dihydrobenzo[e][1,4,2]dithiazine 1,1-dioxide (3ab). White solid,
Yield 0.087 g (83%). Mp 160-162 oC; Rf = 0.43 (95:5 hexane/ethyl
acetate); IR (neat) ν 2951, 2836, 1613, 1503, 1348, 1243, 1186,
1034, 992, 899, 834, 811, 733 cm-1; 1H NMR (500 MHz, CDCl3) δ
(ppm) 7.85 (d, J = 8.0 Hz, 1H), 7.24 (d, J = 8.0 Hz, 1H), 7.13 (s, 1H),
6.95-6.92 (m, 2H), 6.89-6.87 (m, 2H), 3.84 (s, 3H), 3.50 (s, 3H), 2.39
(s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 157.0, 147.0, 144.3,
139.7, 133.4, 129.8, 128.4, 128.1, 124.0, 122.0, 114.6, 55.5, 32.0,
21.6; HRMS (ESI) Calcd. for C16H17N2O3S2 (M++H): m/z 349.0675,
Found: 349.0685.
(Z)-2,6-Dimethyl-3-((4-(trifluoromethyl)phenyl)imino)-2,3-
dihydrobenzo[e][1,4,2]dithiazine 1,1-dioxide (3ac). White solid,
Yield 0.089 g (77%). Mp 146-148 oC; Rf = 0.53 (95:5 hexane/ethyl
acetate); IR (KBr) ν 2951, 1913, 1604, 1412, 1353, 1324, 1177, 1121,
1060, 994, 902, 848, 796, 746, 680, 633, 604 cm-1; 1H NMR (500
MHz, CDCl3) δ (ppm) 7.89 (d, J = 8.0 Hz, 1H), 7.65 (d, J = 8.5 Hz, 2H),
7.16 (s, 1H), 7.03 (d, J = 8.0 Hz, 2H), 3.52 (s, 3H), 2.41 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ (ppm) 149.8, 147.9, 144.6, 133.1, 129.4,
129.1, 128.5, 126.7 (q, 33.0 Hz), 126.6 (q, 7.0 Hz), 124.2 (q, 270.0
Hz), 121.3, 31.9, 21.5; HRMS (ESI) Calcd. for C16H14F3N2O2S2 (M++H):
m/z 387.0443. Found: 387.0448.
Synthesis of the precursors 2-Iodobenzenesulfonamides 1a−j and
26, 13
8b-c: Precursors 1a-j25,
were procured locally or prepared
according to literature procedures. Compounds 642 and 8a-c43 were
prepared by using literature procedures, but precursors 8b-c are
new.
N-(2-iodo-4-methylphenyl)-4-methylbenzenesulfonamide
(8b).
White solid, Yield 1.45 g (89%). Mp 130-132 oC; Rf = 0.53 (95:5
hexane/ethyl acetate); IR (neat) ν 3251, 2920, 1745, 1597, 1482,
1402, 1375, 1333, 1304, 1257, 1224, 1183, 1164, 1090, 1035, 968,
892, 857, 830, 811, 785, 706, 670 cm-1; 1H NMR (500 MHz, CDCl3) δ
(ppm) 7.61 (br m, 2H), 7.54-7.47 (br m, 2H), 7.21 (br m, 2H), 7.12 (s,
1H), 6.69 (s, 1H), 238 (s, 3H), 2.24 (s, 3H); 13C NMR (125 MHz, CDCl3)
δ (ppm) 144.1, 139.3, 137.2, 136.1, 135.0, 130.2, 129.6, 127.5,
122.9, 92.8, 21.6, 20.2; LC/MS: m/z 388 [M + 1]+ ; Anal. calcd for
C14H14INO2S: C, 43.42; H, 3.64; N, 3.62. Found C, 43.36; H, 3.59; N,
3.66.
N-(2-iodophenyl)thiophene-2-sulfonamide (8c). White solid, Yield
o
2.1 g (77%). Mp 138-141 C; Rf = 0.53 (95:5 hexane/ethyl acetate);
(Z)-3-((3-Chlorophenyl)imino)-2,6-dimethyl-2,3-
IR (neat) ν 3243, 3115, 1735, 1575, 1502, 1470, 1442, 1329, 1273,
1221, 1148, 1091, 1068, 1043, 1012, 943, 902, 857, 834, 749, 710,
675, 633 cm-1; 1H NMR (500 MHz, CDCl3) δ (ppm) 7.73-7.70 (m, 2H),
7.59-7.58 (m, 1H), 7.49-7.48 (m, 1H), 7.39-7.36 (m, 1H), 7.04-7.03
(m, 1H), 6.93-6.90 (m, 2H); 13C NMR (125 MHz, CDCl3) δ (ppm)
139.2, 139.1, 137.2, 133.1, 133.0, 129.6, 127.5, 127.4, 123.4, 93.0;
LC/MS: m/z 366 [M + 1]+ ; Anal. calcd for C10H8INO2S2: C, 32.89; H,
2.21; N, 3.84. Found C, 32.83; H, 2.26; N, 3.81.
dihydrobenzo[e][1,4,2]dithiazine 1,1-dioxide (3ad). White solid,
Yield 0.089 g (84%). Mp 186-188 oC; Rf = 0.53 (95:5 hexane/ethyl
acetate); IR (KBr) ν 2950, 1622, 1585, 1464, 1351, 1187, 1046, 994,
1
932, 817, 681 cm-1; H NMR (500 MHz, CDCl3) δ (ppm) 7.88 (d, J =
8.0 Hz, 1H), 7.32 (dd→t, J = 8.0 Hz, 1H), 7.29-7.27 (m, 1H), 7.28-7.23
(m, 2H), 6.95-6.94 (m, 1H), 6.83 (d, J = 8 Hz, 1H), 3.50 (s, 3H), 2.41
(s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 148.0, 147.8, 144.4,
134.9, 133.2, 130.4, 129.4, 128.5, 129.0, 124.7, 124.2, 121.2, 119.3,
31.9, 21.6; HRMS (ESI) Calcd. for C15H14ClN2O2S2 (M++H): m/z
353.0180, 355.0150. Found: 353.0185, 355.0146.
(Z)-3-(Cyclohexylimino)-2,6-dimethyl-2,3-
General procedure for the [Cu]-catalysed reaction of 2-
iodobenzenesulfonamides with isothiocyanates and isocyanates
dihydrobenzo[e][1,4,2]dithiazine 1,1-dioxide (3ae). White solid,
Yield 0.075 g (77%). Mp 147-150 oC; Rf = 0.60 (95:5 hexane/ethyl
acetate); IR (neat) ν 2932, 2855, 1625, 1588, 1448, 1348, 1174,
1050, 996, 827, 782, 679, 633 cm-1; 1H NMR (500 MHz, CDCl3) δ
(ppm) 7.84 (d, J = 8.0 Hz, 1H), 7.26 (s, 1H), 7.23 (d, J = 8.0 Hz, 1H),
3.54-3.49 (m, 1H), 3.31 (s, 3H), 2.43 (s, 3H), 1.82-1.76 (m, 4H), 1.67-
1.63 (m, 1H), 1.49-1.27 (m, 5H); 13C NMR (100 MHz, CDCl3) δ (ppm)
A mixture of 2-iodobenzene sulfonamide (0.3 mmol), phenyl
isothiocyanate/ isocyanate (0.36 mmol), CuI (5 mol%), and ligand
(10 mol%) was taken in a Schlenk tube under nitrogen atmosphere.
To this, THF (2 mL) was added, and the mixture was stirred at 80 °C
(oil bath temperature) for 12 h. The completion of the reaction was
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 7
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 8 of 14
ARTICLE
Journal Name
144.0, 141.4, 134.2, 129.9, 128.5, 127.9, 124.1, 59.0, 33.4, 32.1, MHz, CDCl3) δ (ppm) 7.90 (d, J = 8.4 Hz, 1H), 7.35 (d, J = 8.4 Hz, 2H),
25.6, 24.4, 21.5; HRMS (ESI) Calcd. for C15H20N2O2S2Na m/z (M+ + 6.95-6.93 (m, 1H), 6.86 (d, J = 8.4 Hz, 2H), 6.83 -6.83 Vi(emw ,Ar1tiHcle),O3n.l8in4e
DOI: 10.1039/C9OB00994A
2
0
Na): m/z 347.0858. Found: 347.0864.
(s, 3H), 3.50 (s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 162.9,
147.5, 145.1, 131.5, 130.1, 129.5, 128.1, 126.1, 122.4, 113.4, 113.0,
(Z)-6-Methoxy-2-methyl-3-(phenylimino)-2,3-
dihydrobenzo[e][1,4,2]dithiazine 1,1-dioxide (3ba). White solid, 56.0, 31.8; HRMS (ESI) Calcd. for C15H14ClN2O3S2 (M++H): m/z
Yield 0.086 g (86%). Mp 159-162 oC; Rf = 0.53 (95:5 hexane/ethyl 369.0129, 371.0099. Found: 369.0134, 371.0102.
acetate); IR (neat) ν 3024, 2946, 1623, 1588, 1478, 1341, 1279,
(Z)-6-Methoxy-2-methyl-3-(p-tolylimino)-2,3-
1232, 1188, 1113, 1047, 896, 771, 700, 617 cm-1; 1H NMR (500 MHz, dihydrobenzo[e][1,4,2]dithiazine 1,1-dioxide (3bi). White solid,
CDCl3) δ (ppm) 7.90 (d, J = 9.0 Hz, 1H), 7.42-7.39 (m, 2H), 7.21 Yield 0.077 g (74%). Mp 158-160 oC; Rf = 0.53 (95:5 hexane/ethyl
(d→ft, J = 7.5 Hz, 1H), 6.96-6.92 (m, 3H), 6.825-6.820 (d, J = 2.5 Hz, acetate); IR (neat) ν 2945, 1606, 1585, 1504, 1478, 1346, 1276,
1H), 3.83 (s, 3H), 3.52 (s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 1235, 1188, 1114, 1047, 900, 822, 807, 734, 682 cm-1; 1H NMR (400
162.8, 146.8, 146.6, 131.8, 129.4, 128.2, 126.0, 124.8, 121.0, 113.3, MHz, CDCl3) δ (ppm) 7.89 (d, J = 8.8 Hz, 1H), 7.21 (d, J = 8.0 Hz, 2H),
112.9, 55.9, 31.8; HRMS (ESI) Calcd. for C15H15N2O3S2 (M++H): m/z 6.93-6.91 (m, 1H), 6.86-6.82 (m, 3H), 3.82 (s, 3H), 3.51 (s, 3H), 2.40
335.0519. Found: 335.0523.
(s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 162.8, 146.6, 144.0,
134.4, 131.9, 130.0, 128.2, 126.0, 120.8, 113.2, 112.9, 55.9, 31.8,
(Z)-3-((3-Chlorophenyl)imino)-6-methoxy-2-methyl-2,3-
dihydrobenzo[e][1,4,2]dithiazine 1,1-dioxide (3bd). White solid, 21.0; HRMS (ESI) Calcd. for C16H17N2O3S2 (M++H): m/z 349.0675.
Yield 0.080 g (72%). Mp 205-207 oC; Rf = 0.53 (95:5 hexane/ethyl Found: 349.0685.
acetate); IR (neat) ν 2945, 1626, 1585, 1475, 1347, 1278, 1234,
(Z)-3-(Mesitylimino)-6-methoxy-2-methyl-2,3-
1
1188, 1116, 1046, 995, 923, 815, 736, 697 cm-1; H NMR (400 MHz, dihydrobenzo[e][1,4,2]dithiazine 1,1-dioxide (3bj). White solid,
CDCl3) δ (ppm) 7.90 (d, J = 8.8 Hz, 1H), 7.32 (d→t, J = 8.0 Hz, 1H), Yield 0.084 g (74%). Mp 198-200 oC; Rf = 0.62 (95:5 hexane/ethyl
7.18-7.15 (m, 1H), 6.96-6.93 (m, 2H), 6.85-6.81 (m, 2H), 3.84 (s, 3H), acetate); IR (neat) ν 2940, 1625, 1586, 1478, 1340, 1189, 1048, 886,
3.50 (s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 162.9, 147.82, 857, 736, 680 cm-1; H NMR (500 MHz, CDCl3) δ (ppm) 7.92 (d, J =
1
147.80, 134.9, 131.4, 128.0, 126.1, 124.7, 121.2, 119.3, 113.5, 113.0, 9.0 Hz, 1H), 6.94-6.91 (m, 3H), 6.80-6.79 (m, 1H), 3.83 (s, 3H), 3.57
56.0, 31.8; HRMS (ESI) Calcd. for C15H14ClN2O3S2 (M++H): m/z (s, 3H), 2.33 (s, 3H), 2.11 (s, 6H); 13C NMR (125 MHz, CDCl3) δ (ppm)
369.0129, 371.0099. Found: 369.0137, 371.0113.
162.8, 146.9, 141.3, 133.9, 132.2, 129.0, 128.0, 127.8, 126.2, 113.1,
112.5, 55.8, 31.7, 20.9, 17.7; HRMS (ESI) Calcd. for C18H21N2O3S2
(Z)-3-(Cyclohexylimino)-6-methoxy-2-methyl-2,3-
dihydrobenzo[e][1,4,2]dithiazine 1,1-dioxide (3be). White solid, (M++H): m/z 377.0988. Found: 377.0993.
Yield 0.082 g (80%). Mp 150-152 oC; Rf = 0.60 (95:5 hexane/ethyl
(Z)-3-(Allylimino)-6-methoxy-2-methyl-2,3-
acetate); IR (neat) ν 2930, 2854, 1625, 1585, 1477, 1345, 1277, dihydrobenzo[e][1,4,2]dithiazine 1,1-dioxide (3bk). White solid,
1
1235, 1174, 1115, 1047, 995, 964, 858, 830, 736, 680, 635 cm-1; H Yield 0.056 g (62%). Mp 77-79 oC; Rf = 0.48 (95:5 hexane/ethyl
NMR (400 MHz, CDCl3) δ (ppm) 7.88 (d, J = 8.4 Hz, 1H), 6.95-6.89 acetate); IR (neat) ν 2946, 2844, 1624, 1586, 1478, 1412, 1278,
1
(m, 2H), 3.88 (s, 3H), 3.54-3.49 (m, 1H), 3.31 (s, 3H), 1.82-1.76 (m, 1240, 1176, 1116, 1048, 827, 683 cm-1; H NMR (500 MHz, CDCl3) δ
4H), 1.67-1.64 (m, 1H), 1.51-1.30 (m, 5H); 13C NMR (100 MHz, CDCl3) (ppm) 7.88 (d, J = 9.0 Hz, 1H), 6.95-6.91 (m, 2H), 6.05-5.97 (m, 1H),
δ (ppm) 162.7, 141.1, 131.9, 129.1, 126.0, 113.1, 112.7, 59.0, 55.9, 5.33-5.28 (m, 1H), 5.19-5.16 (m, 1H), 4.12-4.10 (m, 2H), 3.87 (s, 3H),
33.4, 32.0, 25.6, 24.4; HRMS (ESI) Calcd. for C15H20N2O3S2Na 3.37 (s, 3H); 13C NMR (125 MHz, CDCl3) δ (ppm) 162.8, 144.9, 134.5,
(M++Na): m/z 363.0808. Found: 363.0815.
131.4, 129.0, 126.1, 115.8, 113.2, 112.9, 56.0, 52.4, 31.8; HRMS
(Z)-6-Methoxy-2-methyl-3-((4-nitrophenyl)imino)-2,3-
(ESI) Calcd. for C12H15N2O3S2 (M++H): m/z 299.0519. Found
dihydrobenzo[e][1,4,2]dithiazine 1,1-dioxide (3bf). White solid, 299.0521.
Yield 0.089 g (78%). Mp 247-249 oC; Rf = 0.32 (95:5 hexane/ethyl
(Z)-3-((2-Isopropylphenyl)imino)-6-methoxy-2-methyl-2,3-
acetate); IR (neat) ν 2963, 1580, 1509, 1474, 1343, 1262, 1187, dihydrobenzo[e][1,4,2]dithiazine 1,1-dioxide (3bl). White solid,
1
1018, 856, 793, 700 cm-1; H NMR (500 MHz, CDCl3) δ (ppm) 8.30- Yield 0.090 g (80%). Mp 78-80 oC; Rf = 0.62 (95:5 hexane/ethyl
8.27 (m, 2H), 7.93 (d, J = 8.5 Hz, 1H), 7.07-7.04 (m, 2H), 6.99-6.97 acetate); IR (neat) ν 2962, 1626, 1586, 1479, 1349, 1235, 1047,
(m, 1H), 6.85-6.84 (m, 1H), 3.86 (s, 3H), 3.53 (s, 3H); 13C NMR (100 1183, 1046, 901, 791, 753, 681 cm-1; H NMR (400 MHz, CDCl3) δ
1
MHz, CDCl3) δ (ppm) 163.1, 152.7, 148.1, 144.6, 130.8, 127.8, 126.3, (ppm) 7.92 (d, J = 8.8 Hz, 1H), 7.39-7.37 (m, 1H), 7.24-7.20 (m, 2H),
125.3, 121.7, 113.7, 113.1, 56.0, 31.8; HRMS (ESI) Calcd. For 6.94-6.92 (m, 1H), 6.88-6.84 (m, 1H), 6.823-6.820 (m, 1H), 3.83 (s,
C15H13N3O5S2Na (M++Na): m/z 402.0189. Found: 402.0196.
(Z)-4-((6-Methoxy-2-methyl-1,1-
3H), 3.56 (s, 3H), 3.07-2.96 (m, 1H), 1.23 (d, J = 7.2 Hz, 6H); 13C NMR
(100 MHz, CDCl3) δ (ppm) 162.8, 146.3, 144.0, 139.7, 132.0, 128.2,
126.4, 126.2, 126.1, 125.3, 120.4, 113.1, 112.8, 55.9, 31.8, 28.5,
dioxidobenzo[e][1,4,2]dithiazin-3(2H)-ylidene)amino)benzonitrile
(3bg). White solid, Yield 0.093 g (86%). Mp 229-232 oC; Rf = 0.32 22.9. HRMS (ESI) Calcd. for C18H21N2O3S2 (M++H): m/z 377.0988.
(95:5 hexane/ethyl acetate); IR (neat) ν 2950 (w), 2226, 1624, 1585, Found: 377.0994.
1478, 1350, 1278, 1235, 1190, 1115, 1046, 901, 846, 798, 736, 694
(Z)-3-(Butylimino)-6-methoxy-2-methyl-2,3-
cm-1; 1H NMR (500 MHz, CDCl3) δ (ppm) 7.93 (d, J = 9.0 Hz, 1H), dihydrobenzo[e][1,4,2]dithiazine 1,1-dioxide (3bm). White solid,
7.70-7.68 (m, 2H), 7.03-7.01 (m, 2H), 6.98-6.96 (m, 1H), 6.85-6.84 Yield 0.060 g (64%). Mp 60-62 oC; Rf = 0.53 (95:5 hexane/ethyl
(m, 1H), 3.86 (s, 3H), 3.51 (s, 3H); 13C NMR (100 MHz, CDCl3) δ acetate); IR (neat) ν 2957, 2931, 1629, 1586, 1477, 1438, 1345,
(ppm) 163.0, 150.7, 148.0, 133.6, 130.9, 127.8, 126.3, 122.0, 119.0, 1278, 1239, 1175, 1115, 1048, 828, 808, 680 cm-1; 1H NMR (400
113.6, 113.1, 108.1, 56.0, 31.8; HRMS (ESI) Calcd. for C16H14N3O3S2 MHz, CDCl3) δ (ppm) 7.87 (d, J = 8.4 Hz, 1H), 6.94-6.89 (m, 2H), 3.87
(M++H): m/z 360.0471. Found: 360.0496.
(s, 3H), 3.42 (t, J = 7.2 Hz, 2H), 3.31 (s, 3H), 1.71-1.64 (m, 2H), 1.48-
(Z)-3-((4-Chlorophenyl)imino)-6-methoxy-2-methyl-2,3-
1.39 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
dihydrobenzo[e][1,4,2]dithiazine 1,1-dioxide (3bh). White solid, (ppm) 162.7, 143.2, 131.7, 129.0, 113.1, 112.8, 55.9, 50.0, 32.7,
Yield 0.094 g (85%). Mp 148-150 oC; Rf = 0.53 (95:5 hexane/ethyl 31.8, 20.5, 13.9; HRMS (ESI) Calcd. for C13H19N2O3S2 (M++H): m/z
acetate); IR (neat) ν 2947, 1619, 1585, 1481, 1439, 1349, 1277, 315.0832. Found: 315.0837.
1235, 1188, 1116, 1046, 899, 835, 784, 682, 659 cm-1; 1H NMR (400
8 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 9 of 14
Organic & Biomolecular Chemistry
Please do not adjust margins
Journal Name
ARTICLE
(Z)-6-(tert-Butyl)-2-methyl-3-(phenylimino)-2,3-
acetate); IR (neat) ν 2961, 1619, 1586, 1462, 1444, 1351, 1264,
View Article Online
dihydrobenzo[e][1,4,2]dithiazine 1,1-dioxide (3ca). White solid, 1183, 1118, 993, 901, 831, 790, 761, 681,D6O2I8: 1c0m.10-13;9/HC9NOMB0R09(4904A0
Yield 0.095 g (88%). Mp 140-142 oC; Rf = 0.60 (95:5 hexane/ethyl MHz, CDCl3) δ (ppm) 8.08 (d, J = 8.0 Hz, 1H), 7.67-7.65 (m, 1H), 7.56-
acetate); IR (neat) ν 2964, 1620, 1587, 1351, 1269, 1191, 1048, 993, 7.54 (m, 3H), 7.51-7.45 (m, 3H), 7.42-7.39 (m, 1H), 7.26-7.23 (m,
901, 832, 769, 696 cm-1; 1H NMR (500 MHz, CDCl3) δ (ppm) 7.92 (d, 2H), 6.92-6.89 (m, 1H), 3.61 (s, 3H), 3.08-3.01 (m, 1H), 1.25 (d, J =
J = 8.5 Hz, 1H), 7.48-7.46 (m, 1H), 7.43-7.40 (m, 2H), 7.35-7.34 (m, 6.8 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ (ppm) 146.4, 146.3, 144.0,
1H), 7.23-7.20 (m, 1H), 6.97-6.95 (m, 2H), 3.53 (s, 3H), 1.31 (s, 9H); 139.7, 138.3, 134.5, 130.7, 129.2, 129.1, 127.3, 126.5, 126.47,
13C NMR (100 MHz, CDCl3) δ (ppm) 157.4, 147.1, 146.6, 133.2, 126.43, 126.3, 126.0, 125.4, 124.7, 120.4, 32.0, 28.5, 23.0; HRMS
129.5, 129.4, 125.2, 124.8, 124.7, 124.0, 121.0, 35.4, 31.9, 30.9; (ESI) Calcd. for C23H23N2O2S2 (M++H): m/z 423.1195, Found:
HRMS (ESI) Calcd. for C18H21N2O2S2 (M++H): m/z 361.1039. Found: 423.1200.
1
361.1048.
(Z)-6-(tert-Butyl)-2-methyl-3-((4-
(trifluoromethyl)phenyl)imino)-2,3-
(Z)-2-Benzyl-6-methyl-3-(phenylimino)-2,3-
dihydrobenzo[e][1,4,2]dithiazine 1,1-dioxide (3ea). White solid.
o
Yield: 0.102 g (86%). Mp: 167-169 C; Rf = 0.43 (95:5 hexane/ethyl
dihydrobenzo[e][1,4,2]dithiazine 1,1-dioxide (3cc). White solid, acetate); IR (KBr) ν 2921, 1617, 1587, 1342, 1176, 1115, 1052, 1021,
Yield 0.102 g (80%). Mp 218-220 oC; Rf = 0.60 (95:5 hexane/ethyl 872, 767, 752, 698 cm-1; 1H NMR (500 MHz, CDCl3) δ (ppm) 7.91 (d, J
acetate); IR (KBr) ν 2962, 1623, 1605, 1352, 1324, 1271, 1193, 1159, = 8.0 Hz, 1H), 7.39-7.34 (m, 4H), 7.30-7.26 (m, 4H), 7.0-7.12 (m, 1H),
1120, 1065, 902, 847, 797, 743, 634 cm-1; 1H NMR (500 MHz, CDCl3) 7.11 (s, 1H), 6.80 (d, J = 7.5 Hz, 2H), 5.34 (s, 2H), 2.39 (s, 3H); 13C
δ (ppm) 7.93 (d, J = 10.5 Hz, 1H), 7.66 (d, J = 10.5 Hz, 2H), 7.51 (dd, J NMR (100 MHz, CDCl3) δ (ppm) 146.5, 145.9, 144.2, 136.3, 134.0,
= ~ 10.5, 2.0 Hz, 1H), 7.362-7.358 (m, 1H), 7.05 (d, J = 10.5 Hz, 2H), 129.7, 129.3, 128.6, 128.41, 128.40, 128.3, 127.6, 124.7, 124.1,
3.53 (s, 3H), 1.32 (s, 9H); δ 13C NMR (100 MHz, CDCl3) δ (ppm) 120.7, 49.1, 21.6; HRMS (ESI) Calcd. for C21H19N2O2S2 (M++H): m/z
157.7, 149.8, 148.1, 133.1, 129.0, 126.7 (q, 33.0 Hz), 126.6 (q, 7.0 395.0882. Found: 395.0889.
Hz), 125.2, 125.0, 124.1 (q, 270.0 Hz), 121.3, 35.5, 31.9, 30.9; HRMS
(Z)-2-Benzyl-6-methyl-3-((4-nitrophenyl)imino)-2,3-
(ESI) Calcd. for C19H20F3N2O2S2 (M++H): m/z 429.0913. Found: dihydrobenzo[e][1,4,2]dithiazine 1,1-dioxide (3ef). White solid,
429.0921. This compound was crystallised from DCM/hexane (2:1) Yield 0.105 g (80%). Mp 98-100 oC; Rf = 0.38 (95:5 hexane/ethyl
mixture at 25 oC. X-ray structure was determined for this acetate); IR (neat) ν 3060, 1620, 1584, 1514, 1341, 1182, 1112,
compound.
(Z)-6-(tert-Butyl)-3-((4-chlorophenyl)imino)-2-methyl-2,3-
1056, 880, 852, 781, 700, 653 cm-1; 1H NMR (500 MHz, CDCl3) δ
(ppm) 8.22-8.21 (m, 2H), 8.208-8.208 (m, 1H), 7.94 (d, J = 8.0 Hz,
dihydrobenzo[e][1,4,2]dithiazine 1,1-dioxide (3ch). White solid, 1H), 7.34-7.27 (m, 5H), 7.15 (s, 1H), 6.88-6.86 (m, 2H), 5.31 (s, 2H),
Yield 0.101 g (85%). Mp 192-194 oC; Rf = 0.60 (95:5 hexane/ethyl 2.43 (s, 3H); 13C NMR (125 MHz, CDCl3) δ (ppm) 152.5, 147.5, 144.7,
acetate); IR (neat) ν 2958, 1623, 1585, 1481, 1350, 1192, 1114, 144.6, 135.9, 133.7, 128.8, 128.7, 128.5, 128.3, 127.8, 125.3, 124.3,
1047, 899, 835, 790, 663, 644 cm-1; 1H NMR (500 MHz, CDCl3) δ 121.4, 49.3, 21.6; HRMS (ESI) Calcd. for C21H18N3O4S2 (M++H): m/z
(ppm) 7.92 (d, J = 8.0 Hz, 1H), 7.50-7.48 (m, 1H), 7.38-7.36 (m, 3H), 440.0733. Found: 440.0738.
6.91-6.88 (m, 2H), 3.51 (s, 3H), 1.32 (s, 9H); 13C NMR (100 MHz,
(Z)-4-((2-Benzyl-6-methyl-1,1-dioxidobenzo[e][1,4,2]dithiazin-
CDCl3) δ (ppm) 157.6, 147.8, 145.2, 133.2, 130.1, 129.9, 129.2, 3(2H)-ylidene)amino)benzonitrile (3eg). White solid. Yield: 0.096 g
125.2, 124.9, 124.1, 122.4, 35.5, 31.9, 30.9; HRMS (ESI) Calcd. for (76%). Mp 120-122 oC; Rf = 0.38 (95:5 hexane/ethyl acetate); IR
C18H20ClN2O2S2 (M++H): m/z 395.0649, 397.0620. Found: 395.0653, (neat) ν 2962, 2226, 1622, 1593, 1497, 1355, 1182, 1056, 878, 846,
397.0615.
(Z)-2-Methyl-6-phenyl-3-((4-(trifluoromethyl)phenyl)imino)-
816, 734, 700, 676 cm-1; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.93 (d, J
= 8.4 Hz, 1H), 7.65-7.62 (m, 2H), 7.33-7.26 (m, 6H), 7.14 (s, 1H),
2,3-dihydrobenzo[e][1,4,2]dithiazine 1,1-dioxide (3dc). White 6.85-6.82 (m, 2H), 5.30 (s, 2H), 2.42 (s, 3H); 13C NMR (100 MHz,
solid, Yield 0.106 g (79%). Mp 171-173 oC; Rf = 0.65 (95:5 CDCl3) δ (ppm) 150.6, 147.2, 144.6, 135.9, 133.7, 133.5, 128.8,
hexane/ethyl acetate); IR (neat) ν 3060, 2946, 1602, 1505, 1459, 128.7, 128.4, 128.3, 127.8, 124.3, 121.7, 119.0, 108.0, 49.2, 21.6;
1402, 1354, 1324, 1064, 902, 849, 763, 639, 603 cm-1; 1H NMR (400 HRMS (ESI) Calcd. for C22H18N3O2S2 (M++H): m/z 420.0835. Found:
MHz, CDCl3) δ (ppm) 8.07 (d, J = 8.0 Hz, 1H), 7.70-7.66 (m, 3H), 7.57- 420.0838.
7.53 (m, 3H), 7.51-7.45 (m, 3H), 7.06 (d, J = 8.0 Hz, 2H), 3.57 (s, 3H);
(Z)-3-Methyl-2-(phenylimino)-2,3-dihydronaphtho[1,2-
13C NMR (100 MHz, CDCl3) δ (ppm) 149.7, 147.8, 146.6, 138.1, e][1,4,2]dithiazine 4,4-dioxide (3fa). (Isomers ratio 3:1). White
134.3, 129.9, 129.25, 129.22, 127.8 (q, 33.0 Hz), 126.7 (q, 7.0 Hz), solid, Yield 0.096 g (90%). Mp 179-181 oC; Rf = 0.53 (95:5
124.8 (q, 270.0 Hz), 121.3, 32.0; HRMS (ESI) Calcd. for hexane/ethyl acetate); IR (KBr) ν 2941, 1620, 1590, 1485, 1348,
C21H16F3N2O2S2 (M++H): m/z 449.0600. Found: 449.0604.
(Z)-2-Methyl-6-phenyl-3-(p-tolylimino)-2,3-
1265, 1187, 1147, 1004, 897, 813, 769, 693 cm-1; H NMR (500
1
MHz, CDCl3) (Major isomer) δ (ppm) 8.04-8.00 (m, 2H), 7.93 (d, J =
dihydrobenzo[e][1,4,2]dithiazine 1,1-dioxide (3di). White solid, 8.5 Hz, 2H), 7.69-7.64 (m, 2H), 7.47-7.41 (m, 2H), 7.30-7.25 (m, 1H),
Yield 0.106 g (89%). Mp 165-167 oC; Rf = 0.65 (95:5 hexane/ethyl 7.02 (d, J = 7.5 Hz, 2H), 3.59 (s, 3H); For the minor isomer, peaks at
acetate); IR (neat) ν 3027, 1605, 1584, 1504, 1351, 1188, 1056, 899,
824, 763, 735, 683 cm-1; 1H NMR (500 MHz, CDCl3) δ (ppm) 8.05 (d, J
= 8.5 Hz, 1H), 7.67-7.64 (m, 1H), 7.54-7.50 (m, 3H), 7.49-7.43 (m,
3H), 7.25 (d, J = 8 Hz, 2H), 6.88 (d, J = 8.4 Hz, 2H), 3.57 (s, 3H), 2.41
(s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 146.6, 146.3, 144.0,
138.3, 134.6, 134.5, 130.6, 130.0, 129.2, 129.0, 127.3, 126.6, 126.0,
124.6, 120.8, 32.1, 21.1; HRMS (ESI) Calcd. for C21H19N2O2S2 (M++H):
m/z 395.0882. Found: 395.0889.
 8.53 and 3.58 were clear, but other peaks were merged with the
major isomer; 13C NMR (100 MHz, CDCl3) δ (ppm) 146.5, 134.7,
133.5, 129.8, 129.3, 129.0, 128.3, 128.0, 128.1, 128.0, 124.8, 124.1,
121.0, 31.9 (peaks due to individual isomers could not be
distinguished clearly except for the methyl carbon at  32.2); HRMS
(ESI) Calcd. for C18H15N2O2S2 (M++H): m/z 355.0569. Found:
355.0578.
(Z)-2-((4-Methoxyphenyl)imino)-3-methyl-2,3-
(Z)-3-((2-Isopropylphenyl)imino)-2-methyl-6-phenyl-2,3-
dihydronaphtho[1,2-e][1,4,2]dithiazine 4,4-dioxide (3fb). (Isomers
ratio 3:1). White solid, Yield 0.101 g (88%). Mp 159-161 oC; Rf = 0.53
(95:5 hexane/ethyl acetate); IR (neat) ν 2952, 2834, 1613, 1502,
dihydrobenzo[e][1,4,2]dithiazine 1,1-dioxide (3dl). White solid,
Yield 0.098 g (77%). Mp 195-197 oC; Rf = 0.65 (95:5 hexane/ethyl
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 9
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 10 of 14
ARTICLE
Journal Name
1461, 1346, 1290, 1243, 1186, 1032, 1003, 899, 833, 809, 732, 687, 1H), 3.41 (s, 3H), 2.29 (s, 3H); 13C NMR (125 MHz, CDCl3) δ (ppm)
View Article Online
1
649 cm-1; H NMR (400 MHz, CDCl3) (Major isomer) δ (ppm) 8.03- 150.7, 145.2, 137.7, 137.0, 130.2, 129.3, 12D4O.6I,: 1102.210.73,9/1C291O.7B,0101989.43A,
8.00 (m, 2H), 7.90 (d, J = 8.4 Hz, 2H), 7.67-7.57 (m, 2H), 7.01-6.91 27.2, 22.0; HRMS (ESI) Calcd. for C15H14N2O3SNa (M++Na): m/z
(m, ca 4H), 3.86 (s, 3H), 3.57 (s, 3H); For the minor isomer, peaks at 325.0617. Found: 325.0641.
2,6-Dimethyl-4-(p-tolyl)-2H-benzo[e][1,2,4]thiadiazin-3(4H)-
one 1,1-dioxide (5ab). White solid, Yield 0.078 g (82%). Mp 165-167
oC; Rf = 0.42 (95:5 hexane/ethyl acetate); IR (neat) ν 2920, 1696,
 8.50, 3.86 and 3.56 were clear, but other peaks were merged with
the major isomer [By comparing these data with the 1H NMR
spectrum of the single crystal for which an X-ray structure was
determined,26 the minor isomer is identified as 3fb’]; 13C NMR (100
MHz, CDCl3) δ (ppm) 157.0, 145.5, 139.6, 134.7, 133.6, 129.8, 129.5,
129.3, 129.1, 129.0, 128.0, 127.5, 127.4, 124.9, 124.1, 122.1, 119.3,
114.7, 114.6, 55.5, 31.9 (peaks due to individual isomers could not
be distinguished clearly except for a methyl carbon at  32.3);
HRMS (ESI) Calcd. for C19H16N2O3S2Na (M++Na): m/z 407.0495.
Found: 407.0500.
1
1603, 1515, 1345, 1267, 1179, 1148, 1081, 931, 802, 673 cm-1; H
NMR (500 MHz, CDCl3) δ (ppm) 7.79 (d, J = 8 Hz, 1H), 7.37 (d, J = 8.0
Hz, 2H), 7.23 (d, J = 8.5 Hz, 2H), 7.10 (d, J = 8.0 Hz, 1H), 6.45 (s, 1H),
3.39 (s, 3H), 2.47 (s, 3H), 2.89 (s, 3H); 13C NMR (125 MHz, CDCl3) δ
(ppm) 150.8, 145.3, 139.4, 137.8, 134.4, 130.8, 128.9, 124.6, 122.6,
121.6, 118.4, 27.2, 22.0, 21.3; HRMS (ESI) Calcd. for C16H17N2O3S
(M++H): m/z 317.0954. Found: 317.0960.
4-(4-Chlorophenyl)-2,6-dimethyl-2H-benzo[e][1,2,4]thiadiazin-
3(4H)-one 1,1-dioxide (5ac). White solid. Yield 0.079 g (78%). Mp
162-164 C; Rf = 0.42 (9:1 hexane/ethyl acetate); IR (neat) ν 2957,
(Z)-2-((3-Chlorophenyl)imino)-3-methyl-2,3-
dihydronaphtho[1,2-e][1,4,2]dithiazine 4,4-dioxide (3fd). (Isomers
ratio 3:1). White solid, Yield 0.097 g (84%). Mp 181-183 oC; Rf = 0.53
(95:5 hexane/ethyl acetate); IR (neat) ν 2946, 1623, 1585, 1499,
1464, 1413, 1349, 1314, 1259, 1188, 1004, 923, 867, 814, 784, 739,
o
1702, 1603, 1495, 1423, 1335, 1268, 1175, 1154, 1082, 1020, 927,
849, 808, 746, 669, 612 cm-1; 1H NMR (500 MHz, CDCl3) δ (ppm)
7.82 (d, J = 8.5 Hz, 1H), 7.55 (d, J = 8.5 Hz, 2H), 7.31 (d, J = 8.5 Hz,
2H), 7.12 (d, J ~ 8.5 Hz, 1H), 6.39 (s, 1H), 3.40 (s, 3H), 2.31 (s, 3H);
13C NMR (125 MHz, CDCl3) δ (ppm) 150.6, 145.4, 137.4, 135.5,
135.3, 130.7, 130.4, 124.8, 122.8, 121.9, 118.1, 27.3, 22.0; HRMS
(ESI) Calcd. for C15H14ClN2O3S (M++H): m/z 337.0408, 339.0379.
Found: 337. 0413, 339.0379.
1
697, 649 cm-1. (Major isomer) H NMR (400 MHz, CDCl3) δ (ppm)
8.03-8.00 (m, 2H), 7.92 (d, J = 8.8 Hz, 2H), 7.67-7.66 (m, ca 2H),
7.39-7.32 (m, 1H), 7.20 (d, J ~ 8.8 Hz, 1H), 7.03-7.02 (m, 1H), 6.91-
6.89 (m, 1H), 3.57 (s, 3H); For the minor isomer, peaks at  8.51,
7.00 and 3.56 were clear, but other peaks were merged with the
major isomer; 13C NMR (100 MHz, CDCl3) δ (ppm) 147.7, 146.5,
135.0, 134.6, 133.3, 130.7, 129.44, 129.42, 129.3, 130.0, 129.44,
128.6, 128.2, 127.7, 127.5, 124.8, 124.0, 121.3, 119.4, 31.9 (peaks
due to individual isomers could not be distinguished clearly except
4-(4-Fluorophenyl)-2,6-dimethyl-2H-benzo[e][1,2,4]thiadiazin-
3(4H)-one 1,1-dioxide (5ad). White solid, Yield 0.083 g (86%). Mp
o
178-180 C; Rf = 0.42 (95:5 hexane/ethyl acetate); IR (neat) ν 3075,
2946, 1696, 1603, 1505, 1417, 1345, 1268, 1237, 1175, 1144, 1082,
942, 865, 813, 741, 679 cm-1; 1H NMR (400 MHz, CDCl3) δ (ppm)
7.81 (d, J = 8.0 Hz, 1H), 7.37-7.34 (m, 2H), 7.28-7.25 (m, 2H), 7.13-
7.11 (m, 1H), 6.39 (s, 1H), 3.39 (s, 3H), 2.31 (s, 3H); 13C NMR (100
MHz, CDCl3) δ (ppm) 162.7 (d, J = 248.2 Hz), 150.8, 145.4, 137.6,
132.95, 132.92, 131.2 (d, J = 8.9 Hz), 124.8, 122.8, 121.8, 118.1,
for the methyl carbon at
 32.2); HRMS (ESI) Calcd. for
C18H14ClN2O2S2 (M++H): m/z 389.0180, 391.0150. Found: 389.0185,
391. 0150.
(Z)-2-Methyl-3-(p-tolylimino)-2,3-
dihydrobenzo[e][1,4,2]dithiazine 1,1-dioxide (3gi): Yield: 0.081 g
(85% using 1g, White solid); mp 171-173 oC; Rf = 0.53 (95:5
hexane/ethyl acetate); IR (neat) ν 3090, 2941, 1620, 1580, 1502,
1455, 1434, 1341, 1258, 1271, 1208, 1186, 1171, 1129, 1117, 1054,
992, 941, 900, 826, 806, 759, 733, 713, 674 cm-1; (major isomer) 1H
NMR (500 MHz, CDCl3) δ (ppm) 8.01-7.99 (m, 1H), 7.56-7.53 (m,
1H), 7.48-7.45 (m, 1H), 7.35-7.33 (m, 1H), 7.23-7.21 (m, 2H), 6.85 (d,
J = 8 Hz, 2H), 3.53 (s, 3H), 2.40 (s, 3H); 13C NMR (125 MHz, CDCl3): δ
(ppm) 146.5, 143.9, 136.2, 134.4, 133.0, 130.1, 129.1, 128.1, 127.4,
124.1, 120.8, 32.0, 21.1; HRMS (ESI) Calcd. for C15H15N2O2S2 (M++H):
m/z 319.0569, Found: 319.0578.
117.2 (d,
J = 23.0 Hz), 27.3, 22.0; HRMS (ESI) Calcd. for
C15H13N2O3SNa (M++Na): m/z 343.0523. Found: 343.0530.
4-(4-Bromophenyl)-2,6-dimethyl-2H-benzo[e][1,2,4]thiadiazin-
3(4H)-one 1,1-dioxide1,1-dioxide (5ae). White solid, Yield 0.084 g
(73%). Mp 174-176 oC; Rf = 0.42 (95:5 hexane/ethyl acetate); IR
(neat) ν 1695, 1601, 1482, 1450, 1409, 1311, 1270, 1209, 1151,
1
1094, 1062, 1004, 935, 861, 804, 739, 702, 661, 604, 559 cm-1; H
NMR (500 MHz, CDCl3) δ (ppm) 7.82 (d, J = 8.0 Hz, 1H), 7.73-7.70
(m, 2H), 7.27-7.24 (m, 2H), 7.13-7.11 (m, 1H), 6.40 (s, 1H), 3.39 (s,
3H), 2.32 (s, 3H); 13C NMR (125 MHz, CDCl3) δ (ppm) 150.6, 145.4,
137.4, 136.1, 133.4, 131.1, 124.8, 123.4, 122.8, 122.0, 118.1, 27.3,
21.1; HRMS (ESI) Calcd. for C15H14BrN2O3S (M++H): m/z 380.9903,
382.9883. Found: 380.9905, 382.9923.
(Z)-6-Fluoro-2-methyl-3-(p-tolylimino)-2,3-
dihydrobenzo[e][1,4,2]dithiazine 1,1-dioxide (3hi): Yield 0.078 g
(82%, White solid); mp 179-182 oC; Rf = 0.53 (95:5 hexane/ethyl
acetate); IR (neat) ν 3089, 2949, 1625, 1573, 1501, 1466, 1410,
1386, 1345, 1301, 1260, 1212, 1169, 1126, 1106, 1044, 1000, 931,
901, 854, 816, 734, 714, 683 cm-1; (major isomer) 1H NMR (500
MHz, CDCl3) δ (ppm) 8.02-8.00 (m, 1H), 7.23 (d, J = 8 Hz, 2H), 7.18-
7.16 (m, 1H), 7.15-7.14 (m, 1H), 6.84 (d, J = 8.5 Hz, 2H), 3.53 (s, 3H),
2.40 (s, 3H); 13C NMR (125 MHz, CDCl3) δ (ppm) 164.5 (d, J = 256.2
Hz), 145.6, 143.6, 134.7, 133.1 (d, J = 9.3 Hz), 132.4 (d, J = 3.4 Hz),
130.1, 126.8 (d, J = 9.8 Hz), 120.0, 115.5 (d, J = 25.3 Hz), 114.8 (d, J =
22.7 Hz), 32.2, 21.0; HRMS (ESI) Calcd. for C15H14FN2O2S2 (M++H):
m/z 337.0475, Found: 337.0483.
6-Methoxy-2-methyl-4-(p-tolyl)-2H-benzo[e][1,2,4]thiadiazin-
3(4H)-one 1,1-dioxide (5bb). White solid, Yield 0.092 g (92%). Mp
o
193-195 C; Rf = 0.42 (95:5 hexane/ethyl acetate); IR (neat) ν 3069,
2922, 1691, 1585, 1511, 1446, 1417, 1356, 1311, 1266, 1225, 1168,
1
1135, 1078, 1025, 1004, 935, 837, 804, 739, 690, 669, 608 cm-1; H
NMR (400 MHz, CDCl3) δ (ppm) 7.84 (d, J = 8.8 Hz, 1H), 7.44 (d, J =
8.0 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H), 6.80-6.78 (m, 1H), 6.094-6.088
(m, 1H), 3.70 (s, 3H), 3.39 (s, 3H), 2.45 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ (ppm) 163.8, 150.8, 139.6, 139.4, 134.4, 130.8, 128.9,
124.7, 116.7, 109.1, 103.9, 55.7, 27.1, 21.3; HRMS (ESI) Calcd. for
C16H17N2O4S (M++H): m/z 333.0904. Found: 333.0907.
2,6-Dimethyl-4-phenyl-2H-benzo[e][1,2,4]thiadiazin-3(4H)-one
1,1-dioxide (5aa). White solid, Yield 0.080 g (88%). Mp 176-178 C;
Rf = 0.42 (95:5 hexane/ethyl acetate); IR (neat) ν 2962, 1696, 1603,
o
6-(tert-Butyl)-4-(4-chlorophenyl)-2-methyl-2H-
benzo[e][1,2,4]thiadiazin-3(4H)-one 1,1-dioxide (5cc). White solid,
Yield 0.097 g (85%). Mp 157-159 oC; Rf = 0.42 (95:5 hexane/ethyl
acetate); IR (neat) ν 2953, 2921, 2847, 1687, 1593, 1572, 1495,
1495, 1448, 1412, 1340, 1314, 1268, 1149, 1077, 1025, 937, 818,
1
751, 694, 607 cm-1; H (400 MHz, CDCl3) δ (ppm) 7.82 (d, J = 8 Hz,
1H), 7.61-7.52 (m, 3H), 7.38-7.36 (m, 2H), 7.12-7.09 (m, 1H), 6.39 (s,
10 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 11 of 14
Organic & Biomolecular Chemistry
Please do not adjust margins
Journal Name
ARTICLE
1458, 1417, 1331, 1307, 1266, 1196, 1151, 1090, 1012, 927, 812, 2H), 7.60 (d→t, J = 7.6 Hz, 1H), 7.49-7.43 (m, 3H), 7.36-7.31 (m, 2H),
View Article Online
784, 739, 686, 641, 604 cm-1; 1H NMR (500 MHz, CDCl3) δ (ppm) 7.29-7.16 (m, 1H), 6.87-6.84 (m, 2H), 6.63-6D.6O0I:(1m0.,120H39),/C59.0O2B0(s0,929H4)A,
7.85 (d, J = 8.5 Hz, 1H), 7.55 (d, J = 8.5 Hz, 2H), 7.35-7.33 (m, 3H), 3.81 (s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 156.6, 147.3, 140.5,
6.608-6.605 (m, 1H), 3.37 (s, 3H), 1.18 (s, 9H); 13C NMR (125 MHz, 139.1, 133.3, 133.0, 131.3, 128.9, 128.6, 127.4, 127.0, 126.7, 121.7,
CDCl3) δ (ppm) 158.5, 150.7, 137.3, 135.7, 135.2, 130.7, 130.3, 114.3, 55.4, 49.5; HRMS (ESI) Calcd. for C21H19N2O3S2 (M++H): m/z
122.6, 121.9, 121.4, 114.9, 35.4, 30.8, 27.2; HRMS (ESI) Calcd. for 411.0832. Found: 411.0837.
C18H20ClN2O3S (M++H): m/z 379.0878, 381.0848. Found: 379.0887,
381.0873.
(Z)-3-(Phenylsulfonyl)-N-(4-(trifluoromethyl)phenyl)-3,4-
dihydro-2H-benzo[e][1,3]thiazin-2-imine (7c). White solid, Yield
0.087 g (70%). Mp 142-144 oC; Rf = 0.45 (95:5 hexane/ethyl
4-(4-Fluorophenyl)-2-methyl-6-phenyl-2H-
benzo[e][1,2,4]thiadiazin-3(4H)-one 1,1-dioxide (5dd). White solid, acetate); IR (KBr) ν 3065, 1632, 1604, 1476, 1446, 1358, 1324, 1252,
Yield 0.100 g (87%). Mp 189-191 oC; Rf = 0.42 (95:5 hexane/ethyl 1169, 1121, 1083, 1013, 967, 844, 788, 752, 723, 685 cm-1; 1H NMR
acetate); IR (neat) ν 3052, 2958, 2921, 1699, 1589, 1564, 1511, (500 MHz, CDCl3) δ (ppm) 7. 85 (d, J = 8.5 Hz, 2H), 7.63 (t, J = 7.5 Hz,
1478, 1442, 1409, 1331, 1266, 1221, 1180, 1143, 1078, 1017, 984, 1H), 7.60 (d, J = 8.5 Hz, 2H), 7.52-7.46 (m, 3H), 7.39-7.33 (m, 2H),
914, 825, 800, 763, 747, 682 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.21-7.20 (m, 1H), 6.19 (d, J = 8.0 Hz, 2H), 5.05 (s, 2H); 13C NMR (125
(ppm) 8.02 (d, J = 8.0 Hz, 1H), 7.54-7.51 (m, 1H), 7.46-7.39 (m, 7H), MHz, CDCl3) δ (ppm) 150.3, 148.3, 138.9, 133.5, 133.0, 130.6, 129.1,
7.31-7.28 (m, 2H), 6.807-6.805 (m, 1H), 3.45 (s, 3H); 13C NMR (100 128.7, 128.6, 127.1 (q, 33.0 Hz), 126.7 (q, 270.0 Hz), 126.3 (q, 7.0
MHz, CDCl3) δ (ppm) 162. 7 (d, J = 248.5 Hz), 150.8, 147.5, 138.8, Hz), 125.4, 120.9, 49.5; HRMS (ESI) Calcd. for C21H16F3N2O2S2
138.1, 132.9 (d, J = 3.2 Hz), 131.2 (d, J = 8.8 Hz), 129.2, 129.0, 127.3, (M++H): m/z 449.0600. Found: 449.0605.
123.4, 123.1, 122.8, 117.3 (d, J = 22.9 Hz), 116.5, 27.4; HRMS (ESI)
(Z)-N-(3-Chlorophenyl)-3-(phenylsulfonyl)-3,4-dihydro-2H-
Calcd. for C20H16FN2O3S (M++H): m/z 383.0860. Found 383.0863. benzo[e][1,3]thiazin-2-imine (7d). White solid, Yield 0.101 g (81%).
This compound was crystallised from DCM/hexane (2:1) mixture at Mp 173-174 oC; Rf = 0.45 (95:5 hexane/ethyl acetate); IR (neat) ν
room temperature. X-ray structure was determined for this 3064, 1627, 1585, 1469, 1444, 1357, 1265, 1171, 1083, 966, 889,
1
compound.
2-Methyl-4-(p-tolyl)-2H-benzo[e][1,2,4]thiadiazin-3(4H)-one
782, 752, 728, 688 cm-1; H NMR (500 MHz, CDCl3) δ (ppm) 7.86-
7.84 (m, 2H), 7.63-7.60 (m, 1H), 7.51-7.46 (m, 3H), 7.38-7.32 (m,
o
1,1-dioxide (5gb). White solid, Yield 0.079 g (87%). Mp 169-174 C; 2H), 7.24-7.20 (m, 2H), 7.19-7.09 (m, 1H), 6.62-6.61 (m, 1H), 6.57-
Rf = 0.42 (95:5 hexane/ethyl acetate); IR (neat) ν 3081, 2924, 1678, 6.56 (m, 1H), 5.03 (s, 2H); 13C NMR (125 MHz, CDCl3) δ (ppm) 148.5,
1583, 1510, 1481, 1418, 1331, 1292, 1265, 1232, 1175, 1140, 1106, 139.0, 134.6, 133.5, 133.0, 130.8, 130.1, 129.0, 128.7, 128.6, 127.7,
1077, 1042, 1020, 985, 945, 921, 851, 809, 784, 754, 738, 721, 664, 127.1, 126.6, 124.3, 120.9, 119.0, 49.5; HRMS (ESI) Calcd. for
601 cm-1; 1H NMR (500 MHz, CDCl3) δ (ppm) 7.94-7.92 (m, 1H), 7.47- C20H16ClN2O2S2 (M++H): m/z 415.0336, 417.0312. Found: 415.0307,
7.44 (m, 1H), 7.39 (d, J = 8.0 Hz, 2H), 7.30-7.24 (m, 3H), 6.66 (d, J = 417.0293.
8.5 Hz, 1H), 3.42 (s, 3H), 2.47 (s, 3H); 13C NMR (125 MHz, CDCl3) δ
(Z)-N-Cyclohexyl-3-(phenylsulfonyl)-3,4-dihydro-2H-
(ppm) 150.7, 139.5, 137.8, 134.4, 133.9, 130.8, 128.9, 124.4, 123.6, benzo[e][1,3]thiazin-2-imine (7e). White solid, Yield 0.088 g (76%).
122.6, 118.2, 27.3, 21.4. HRMS (ESI) Calcd. for C15H15N2O3S (M++H): Mp 125-127 oC; Rf = 0.55 (95:5 hexane/ethyl acetate); IR (neat) ν
m/z 303.0798. Found: 303.0806.
2928, 2853, 1634, 1445, 1352, 1263, 1168, 1087, 962, 785, 751,
6-Fluoro-2-methyl-4-(p-tolyl)-2H-benzo[e][1,2,4]thiadiazin-
724, 688 cm-1; 1H NMR (500 MHz, CDCl3) δ (ppm) 7.76-7.74 (m, 2H),
3(4H)-one 1,1-dioxide (5hb). White solid, Yield 0.076 g (79%). Mp 7.53-7.49 (m, 1H), 7.43-7.36 (m, 3H), 7.31-7.28 (m, 2H), 7.22-7.20
o
183-187 C; Rf = 0.42 (95:5 hexane/ethyl acetate); IR (neat) ν 2360, (m, 1H), 4.89 (s, 2H), 3.40-3.33 (m, 1H), 1.74-1.63 (m, 5H), 1.44-1.21
1700, 1610, 1584, 1510, 1490, 1230, 1341, 1310, 1288, 1253, 1210, (m, 5H); 13C NMR (125 MHz, CDCl3) δ (ppm) 142.3, 139.7, 133.6,
1174, 1130, 1108, 1079, 1010, 934, 874, 851, 825, 805, 784, 744, 132.8, 131.4, 128.7, 128.4, 128.2, 127.1, 127.0, 126.8, 60.2, 49.6,
713, 680 cm-1; 1H NMR (500 MHz, CDCl3) δ (ppm) 8.02-8.00 (m, 1H), 32.9, 25.6, 24.4; HRMS (ESI) Calcd. for C20H22N2O2S2Na (M++H): m/z
7.23 (d, J = 8 Hz, 2H), 7.23 (d, J = 8 Hz, 2H), 7.01-7.00 (m, 1H), 6.43- 409.1015. Found: 409.1030.
6.40 (m, 1H), 3.41 (s, 3H), 2.56 (s, 3H); 13C NMR (125 MHz, CDCl3) δ
(Z)-3-(Phenylsulfonyl)-N-(p-tolyl)-3,4-dihydro-2H-
(ppm) 165.5 (d, J = 253.0 Hz), 150.6, 140.4 (d, J = 10.7 Hz), 139.92, benzo[e][1,3]thiazin-2-imine (7f). White solid, Yield 0.087 g (74%).
133.90, 131.1, 128.8, 125.4 (d, J = 11.3 Hz), 120.4, 111.3 (d, J = 23.5 Mp 159-162 oC; Rf = 0.53 (95:5 hexane/ethyl acetate); IR (KBr) ν
Hz), 105.7 (d, J = 28.0 Hz), 27.5, 21.4; HRMS (ESI) Calcd. for 3049, 2930, 1629, 1503, 1475, 1355, 1169, 1082, 964, 823, 789,
C15H14FN2O3S (M++H): m/z 321.0704. Found: 321.0710.
(Z)-N-Phenyl-3-(phenylsulfonyl)-3,4-dihydro-2H-
751, 722, 684 cm-1; 1H NMR (500 MHz, CDCl3) δ (ppm) 7.84 (d, J = 7
Hz, 2H), 7.59 (t, J = 7.5 Hz, 1H), 7.49-7.43 (m, 3H), 7.35-7.29 (m, 2H),
benzo[e][1,3]thiazin-2-imine (7a). White solid, Yield 0.081 g (71%). 7.18-7.16 (m, 1H), 7.12 (d, J = 8 Hz, 2H), 6.68 (d, J = 8 Hz, 2H), 5.03
Mp 195-197 oC; Rf = 0.53 (95:5 hexane/ethyl acetate); IR (neat) ν (s, 2H), 2.35 (s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 147.2,
3063, 1626, 1590, 1481, 1445, 1355, 1266, 1170, 1082, 965, 791, 144.7, 139.1, 134.0, 133.3, 133.1, 131.3, 129.6, 128.9, 128.64,
1
754, 719, 689 cm-1; H NMR (400 MHz, CDCl3) δ (ppm) 7.86 (d, J = 128.60, 127.4, 127.0, 126.7, 120.5, 49.5, 21.0; HRMS (ESI) Calcd. for
7.6 Hz, 2H), 7.60 (dd →t, J = 7.6 Hz, 1H), 7.50-7.44 (m, 3H), 7.34- C21H19N2O2S2 (M++H): m/z 395.0882. Found: 395.0889.
7.30 (m, 4H), 7.28-7.12 (m, 2H), 6.68-6.66 (m, 2H), 5.04 (s, 2H); 13C
(Z)-N-Mesityl-3-(phenylsulfonyl)-3,4-dihydro-2H-
NMR (100 MHz, CDCl3) δ (ppm) 147.4, 147.3, 139.0, 133.4, 133.0, benzo[e][1,3]thiazin-2-imine (7g). White solid, Yield 0.096 g (76%).
131.2, 129.0, 128.9, 128.6, 127.5, 127.0, 126.7, 124.4, 120.6, 49.5; Mp 180-182 oC; Rf = 0.53 (95:5 hexane/ethyl acetate); IR (neat) ν
HRMS (ESI) Calcd. for C20H17N2O2S2 (M++H): m/z 381.0726. Found: 2915, 1639, 1476, 1445, 1355, 1265, 1170, 1141, 1119, 1085, 792,
381.0730.
(Z)-N-(4-Methoxyphenyl)-3-(phenylsulfonyl)-3,4-dihydro-2H-
746 cm-1; 1H NMR (400 MHz, CDCl3) δ (ppm) 8.06 (d, J = 8.0 Hz, 2H),
7.63-7.59 (m, 1H), 7.52-7.45 (m, 3H), 7.34-7.29 (m, 2H), 7.22-7.18
benzo[e][1,3]thiazin-2-imine (7b). White solid, Yield 0.098 g (80%). (m, 1H), 6.87 (s, 2H), 5.01 (s, 2H), 2.31 (s, 3H), 1.89 (s, 6H); 13C NMR
Mp 172-174 oC; Rf = 0.45 (95:5 hexane/ethyl acetate); IR (KBr) ν (100 MHz, CDCl3) δ (ppm) 146.4, 142.4, 140.0, 133.4, 133.2, 133.0,
1620, 1502, 1446, 1354, 1290, 1242, 1169, 1082, 1032, 964, 832, 131.4, 128.9, 128.7, 128.61, 128.60, 127.9, 127.3, 127.0, 126.4, 50.1,
790, 703, 685 cm-1; 1H NMR (400 MHz, CDCl3) δ (ppm) 7.84-7.82 (m,
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 11
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 12 of 14
ARTICLE
Journal Name
20.9, 17.5; HRMS (ESI) Calcd. for C23H23N2O2S2 (M++H): m/z (d, J = 8.5 Hz, 2H), 7.35-7.31 (m, 3H), 7.31-7.25 (m, 1H), 7.17-7.12
423.1195. Found: 423.1201.
(m, 4H), 6.65-6.63 (m, 1H), 2.61-2.52 (m, 1H), 2.48 (s,V3ieHw),Ar1ti.c0le2O(ndli,neJ
DOI: 10.1039/C9OB00994A
= 7.0 Hz, 6H); 13C NMR (125 MHz, CDCl3) δ (ppm) 151.8, 147.9,
(Z)-N-Ethyl-3-(phenylsulfonyl)-3,4-dihydro-2H-
benzo[e][1,3]thiazin-2-imine (7h). White solid, Yield 0.081 g (81%). 145.2, 140.2, 136.8, 136.0, 129.4, 128.6, 126.7, 126.6, 126.0, 125.1,
Mp 140-145 oC; Rf = 0.45 (95:5 hexane/ethyl acetate; IR (neat) ν 124.6, 123.0, 122.3, 119.4, 115.9, 27.8, 23.3, 21.7; HRMS (ESI)
2970, 1685, 1631, 1445, 1340, 1285, 1266, 1164, 1114, 1072, 967, Calcd. for C23H23N2O2S2 (M++H): m/z 423.1195. Found: 423.1207.
908, 871, 838, 794, 748, 718, 683. cm-1; 1H NMR (500 MHz, CDCl3) δ
(Z)-N-(3,5-Bis(trifluoromethyl)phenyl)-3-tosylbenzo[d]thiazol-
(ppm) 7.75-7.73 (m, 2H), 7.52-7.49 (m, 1H), 7.42-7.35 (m, 3H), 7.29- 2(3H)-imine (9f). White solid, Yield 0.094 g (61%). Mp 130-135 oC; Rf
7.27 (m, 2H), 7.20-7.18 (m, 1H), 4.87 (s, 2H), 3.37 (q, J = 7.5 Hz, 2H), = 0.53 (95:5 hexane/ethyl acetate); IR (neat) ν 2925, 1701, 1603,
1.75 (t, J = 7.5 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ (ppm) 144.5, 1546, 1453, 1422, 1340, 1267, 1216, 1174, 1148, 1076, 1024, 952,
139.5, 133.3, 133.0, 131.1, 128.7, 128.4, 128.3, 127.2, 127.1, 126.7, 813, 735, 647 cm-1; H NMR (400 MHz, CDCl3) δ (ppm) 8.28 (d, J =
1
49.6, 45.8, 15.2; HRMS (ESI) Calcd. for C16H17N2O2S2 (M++H): m/z 8.0 Hz, 1H), 7.97 (d, J = 8.4 Hz, 2H), 7.62 (s, 1H), 7.41-7.37 (m, 3H),
333.0726. Found: 333.0731.
7.31-7.23 (m, 2H), 7.13 (s, 2H). 2.50 (s, 3H); 13C NMR (100 MHz,
(Z)-N-Phenyl-3-tosylbenzo[d]thiazol-2(3H)-imine (9a). White CDCl3) δ (ppm) 155.1, 150.7, 146.2, 136.5, 134.8, 132.9 (m), 129.5.
solid, Yield 0.088 g (77%). Mp 221-223 oC; Rf = 0.53 (95:5 129.0, 127.3, 125.3, 123.1 (q, 270.0 Hz), 121.9, 121.12, 121.10,
hexane/ethyl acetate); IR (neat) ν 1644, 1590, 1453, 1369, 1255, 118.0, 117.9 (m), 116.6, 21.7; HRMS (ESI) Calcd. for C22H15F6N2O2S2
1
1174, 1143, 959, 808, 753, 697, 678, 654 cm-1; H NMR (400 MHz, (M++H): m/z 517.0474. Found: 517.0479.
CDCl3) δ (ppm) 8.24 (d, J = 8.4 Hz, 1H), 8.00 (d, J = 8.4 Hz, 2H), 7.37-
(Z)-N-Ethyl-3-tosylbenzo[d]thiazol-2(3H)-imine (9g). White
7.31 (m, 5H), 7.23-7.12 (m, 3H), 6.77-6.75 (m, 2H), 2.49 (s, 3H); 13C solid, Yield 0.079 g (79%). Mp 110-115 oC; Rf = 0.53 (95:5
NMR (100 MHz, CDCl3) δ (ppm) 152.4, 149.9, 145.5, 136.5, 135.1, hexane/ethyl acetate); IR (neat) ν 2968, 1914, 1651, 1592, 1492,
129.5, 129.3, 128.9, 126.7, 124.8, 124.6, 123.0, 122.2, 120.4, 116.3, 1458, 1397, 1367, 1348, 1307, 1236, 1177, 1145, 1086, 1032, 1009,
21.8; HRMS (ESI) Calcd. for C20H16N2O2S2Na (M++Na): m/z 403.0545. 961, 891, 861, 814, 789, 748, 677, 658 cm-1; 1H NMR (500 MHz,
Found: 403.0552.
CDCl3) δ (ppm) 8.30 (d, J = 8.5 Hz, 1H), 7.87 (d, J = 8.5 Hz, 2H), 7.38-
7.26 (m, 4H), 7.16-7.13 (m, 1H), 3.18 (q, J = 7.5 Hz, 2H), 2.42 (s, 3H),
(Z)-3-Tosyl-N-(4-(trifluoromethyl)phenyl)benzo[d]thiazol-
o
2(3H)-imine (9b). White solid, Yield 0.100 g (75%). Mp 193-195 C; 1.15 (t, J = 7.5 Hz, 3H); 13C NMR (125 MHz, CDCl3): δ (ppm) 149.4,
Rf = 0.53 (95:5 hexane/ethyl acetate; IR (KBr) ν 1642, 1603, 1458, 145.1, 136.5, 135.3, 129.1, 128.8, 126.5, 124.5. 123.3, 122.2, 116.4,
1379, 1260, 1224, 1123, 1065, 1013, 958, 790, 748, 660 cm-1; 1H 50.4, 21.7, 15.2; HRMS (ESI) Calcd. for C16H17N2O2S2 (M++H): m/z
NMR (400 MHz, CDCl3) δ (ppm) 8.27 (d, J = 8.4 Hz, 1H), 7.99 (d, J = 333.0726. Found: 333.0730.
8.4 Hz, 2H), 7.59 (d, J = 8.4 Hz, 2H), 7.37-7.33 (m, 3H), 7.26-7.18 (m,
(Z)-6-methyl-3-tosyl-N-(4-
2H), 6.84 (d, J = 8.4 Hz, 2H), 2.49 (s, 3H); 13C NMR (100 MHz, CDCl3) (trifluoromethyl)phenyl)benzo[d]thiazol-2(3H)-imine (9h). White
δ (ppm) 153.4, 152.7, 145.8, 136.4, 135.0, 129.4, 128.9, 127.0, solid, Yield 0.087 g (62%). Mp 183-185 oC; Rf = 0.53 (95:5
126.9 (q, 33.0 Hz), 126.8 (q, 7.0 Hz), 126.4, 125.0 (q, 270.0 Hz), hexane/ethyl acetate; IR (KBr) ν 2924, 2360, 2113, 1738, 1639,
122.9, 122.4, 122.3, 120.8, 116.3, 21.7; HRMS (ESI) Calcd. for 1600, 1473, 1410, 1371, 1319, 1263, 1222, 1156, 1134, 1103, 1062,
C21H16F3N2O2S2 (M++Na): m/z 449.0600. Found: 449.0607. This 1012, 962, 866, 842 805, 788, 703, 629 cm-1; 1H NMR (500 MHz,
compound was crystallised from ethyl acetate/hexane (2:1) mixture CDCl3) δ (ppm) 8.14 (d, J = 9.0 Hz, 1H), 7.97 (d, J = 8.5 Hz, 2H), 7.59
at 25 oC. X-ray structure was determined for this compound.
(d, J = 8.5 Hz, 2H), 7.36 (d, J = 8.0 Hz, 2H), 7.16-7.14 (m, 1H), 7.05 (s,
(Z)-N-(3-Chlorophenyl)-3-tosylbenzo[d]thiazol-2(3H)-imine
1H), 6.85 (d, J = 8.5 Hz, 2H), 2.49 (s, 3H), 2.36 (s, 3H); 13C NMR (125
(9c). White solid, Yield 0.095 g (77%). Mp 177-179 oC; Rf = 0.53 (95:5 MHz, CDCl3) δ (ppm); 153.6, 152.7, 145.7, 135.2, 135.0, 134.1,
hexane/ethyl acetate; IR (KBr) ν 3065, 2970, 1646, 1584, 1459, 129.4, 128.9, 127.8, 127.5, 126.8 (q, 33.0 Hz), 126.4 (q, 4.0 Hz),
1372, 1246, 1217, 1183, 1086, 1034, 966, 884, 804, 759, 717, 694, 126.4 (J = 32.5 Hz), 123.2, 122.5, 122.3, 120.8, 116.1, 21.8, 20.8;
657 cm-1; 1H NMR (500 MHz, CDCl3) δ (ppm) 8.25 (d, J = 8.0 Hz, 1H), LC/MS: m/z 463 [M + 1]+; Anal. calcd for C22H17F3N2O2S2: C, 57.13; H,
7.97 (d, J = 8.0 Hz, 2H), 7.37-7.32 (m, 3H), 7.27-7.18 (m, 3H), 7.09 (d, 3.71; N, 6.06. Found C, 57.26; H, 3.75; N, 6.12.
J = 7.5 Hz, 1H), 6.69-6.67 (m, 2H), 2.49 (s, 3H); 13C NMR (125 MHz,
(Z)-N-(3-chlorophenyl)-6-methyl-3-tosylbenzo[d]thiazol-2(3H)-
CDCl3) δ (ppm) 153.4, 150.9, 145.7, 136.4, 135.0, 134.9, 130.6, imine (9i). White solid, Yield 0.085 g (66%). Mp 174-177 oC; Rf =
129.4, 128.9, 126.9, 125.0, 124.6, 122.6, 122.2, 120.8, 118.7, 116.3, 0.53 (95:5 hexane/ethyl acetate; IR (KBr) ν 3095, 2922, 1634, 1582,
21.8; HRMS (ESI) Calcd. for C20H16ClN2O2S2 (M++H): m/z 415.0336, 1453, 1401, 1379, 1343, 1307, 1252, 1219, 1185, 1147, 1091, 1067,
417.0307. Found 415.0343, 417.0308.
1
1035, 1013, 964, 887, 863, 787, 754, 717, 688, 669, 631 cm-1; H
(Z)-N-(p-Tolyl)-3-tosylbenzo[d]thiazol-2(3H)-imine (9d). White NMR (500 MHz, CDCl3) δ (ppm) 8.11 (d, J = 8.5 Hz, 1H), 7.95 (d, J =
solid; Yield 0.093 g (78%). Mp 196-198 oC; Rf = 0.53 (95:5 8.5 Hz, 2H), 7.35 (d, J = 8.5 Hz, 2H), 7.24 (t, J = 8.0 Hz, 1H), 7.14-7.10
hexane/ethyl acetate); IR (neat) ν 2920, 1639, 1601, 1503, 1458, (m, 2H), 7.04 (s, 1H), 6.68-6.65 (m, 2H), 2.49 (s, 3H), 2.36 (s, 3H); 13
C
1376, 1258, 1219, 1176, 1138, 958, 746, 660 cm-1; 1H NMR (400 NMR (125 MHz, CDCl3) δ (ppm): 153.6, 150.9, 145.6, 135.1, 135.0,
MHz, CDCl3) δ (ppm) 8.23 (d, J = 8.4 Hz, 1H), 7.98 (d, J = 8.4 Hz, 2H), 134.9, 134.2, 130.5, 129.4, 128.9, 127.6, 124.5, 122.53, 122.45,
7.35-7.33 (m, 3H), 7.32-7.12 (m, 4H), 6.65 (d, J = 8.4 Hz, 2H), 2.47 (s, 120.8, 118.8, 116.2, 21.7, 20.8; LC/MS: m/z 429 [M + 1]+; Anal. calcd
3H), 2.34 (s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 152.1, 147.4, for C22H17ClN2O2S2: C, 58.80; H, 3.99; N, 6.53. Found C, 58.72; H,
145.4, 136.4, 135.2, 134.2, 130.0, 129.3, 128.9, 126.6, 124.8, 120.2, 3.94; N, 6.58.
116.3, 21.8, 21.0; HRMS (ESI) Calcd. for C21H19N2O2S2 (M++H): m/z
395.0882. Found: 395.0891.
(Z)-N-phenyl-3-(thiophen-2-ylsulfonyl)benzo[d]thiazol-2(3H)-
imine (9j). White solid, Yield 0.083 g (74%). Mp 167-169 oC; Rf =
(Z)-N-(2-Isopropylphenyl)-3-tosylbenzo[d]thiazol-2(3H)-imine
(9e). White solid, Yield 0.082 g (65%). Mp 150-152 oC; Rf = 0.60 0.45 (95:5 hexane/ethyl acetate; IR (KBr) ν 3082, 1709, 1638, 1590,
(95:5 hexane/ethyl acetate); IR (neat) ν 2961, 1646, 1458, 1375, 1482, 1453, 1395, 1374, 1339, 1304, 1249, 1215, 1182, 1165, 1130,
1254, 222, 1176, 1139, 1089, 1064, 1032, 959, 793, 749, 677, 659 1090, 1065, 1019, 956, 906, 852, 778, 755, 716, 697, 677, 629, 601;
cm-1; 1H NMR (500 MHz, CDCl3) δ (ppm) 8.27 (d, J = 8.5 Hz, 1H), 7.98 1H NMR (500 MHz, CDCl3) δ (ppm) 8.19-8.18 (m, 1H), 8.02-8.01 (m,
12 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 13 of 14
Organic & Biomolecular Chemistry
Please do not adjust margins
Journal Name
ARTICLE
1H), 7.76-7.75 (m, 1H), 7.40-7.37 (m, 2H), 7.34-7.30 (m, 1H), 7.24-
7.22 (m, 1H), 7.20-7.16 (m, 3H), 6.94-6.92 (m, 2H); 13C NMR (125
MHz, CDCl3) δ (ppm) 152.2, 149.7, 137.6, 135.9, 135.8, 134.7, 129.5,
127.0, 126.7, 125.0, 124.9, 123.0, 122.2 120.5, 116.3; LC/MS: m/z
373 [M + 1]+ ; Anal. calcd for C17H12N2O2S3: C,54.82; H, 3.25; N, 7.52.
Found C, 54.75; H, 3.21; N, 7.56.
P. Fraikin, P. Lestage, L. Danober, J. -Y. Thomas, D. -H.
View Article Online
Caignard and B. Pirotte, J. Med. ChDeOmI:.1,02.0100379,/5C09,O3B105039;9(4eA)
K. C. Majumdar and S. Mondal, Chem. Rev., 2011, 111,
7749.
C. Valente, R. C. Guedes, R. Moreira, J. Iley, J. Gut and P. J.
Rosenthal, Bioorg. Med. Chem. Lett., 2006, 16, 4115.
9
(Z)-N-(3-chlorophenyl)-3-(thiophen-2-
10 (a) J. G. Lombardino, E. H. Wiseman and W. M. Mclamore,
J. Med. Chem., 1971, 14, 1171; (b) J. G. Lombardino and E.
H. Wiseman, J. Med. Chem., 1972, 15, 848; (c) C. Nicolas,
M. Verny, I. Giraud, M. Ollier, M. Rapp, J. C. Maurizis and
J. C. Madelmont, J. Med. Chem., 1999, 42, 5235; (d) S. Xu,
C. A. Rouzer and L. J. Marnett, IUBMB Life, 2014, 66, 803.
11 G. Kumaraswamy, M. Padmaja, B. Markondaiah, N. Jena,
B. Sridhar and M. U. Kiran, J. Org. Chem., 2006, 71, 337.
12 K. H. Ahn, H. H. Baek, S. J. Lee and C. W. Cho, J. Org.
Chem., 2000, 65, 7690.
13 L. Zhuang, J. S. Wai, M. W. Embrey, T. E. Fisher, M. S.
Egbertson, L. S. Payne, Jr; J. Guare, J. P. Vacca, D. J.
Hazuda, P. J. Felock, A. L. Wolfe, K. A. Stillmock, M. V.
Witmer, G. Moyer, W. A. Schleif, L. J. Gabryelski, Y. M.
Leonard, J. J. Lynch, S. R. Michelson and S. D. Young, J.
Med. Chem., 2003, 46, 453.
ylsulfonyl)benzo[d]thiazol-2(3H)-imine (9k). White solid, Yield
0.076 g (62%). Mp 160-163oC; Rf = 0.45 (95:5 hexane/ethyl acetate;
IR (KBr) ν 2923, 2048, 1630, 1577, 1472, 1369, 1306, 1272, 1247,
1222, 1170, 1153, 1135, 1084, 1070, 1017, 967, 866, 811, 799, 778,
694, 662, 613; 1H NMR (500 MHz, CDCl3) δ (ppm) 8.20-8.18 (m, 1H),
8.00-7.99 (m, 1H), 7.78-7.77 (m, 1H), 7.35-7.29 (m, 2H), 7.27-7.24
(m, 1H), 7.21-7.13 (m, 3H), 6.93-6.92 (m, 1H), 6.85-6.83 (m, 1H); 13
C
NMR (125 MHz, CDCl3) δ (ppm) 153.2, 150.7, 137.4, 135.9, 135.8,
135.00, 134.96, 130.6, 127.1, 126.9, 125.1, 124.8, 122.6, 122.3,
120.9, 118.9, 116.3; LC/MS: m/z 407 [M + 1]+ ; Anal. calcd for
C17H12N2O2S3: C, 50.18; H, 2.72; N, 6.88. Found C, 50.09; H, 2.69; N,
6.92.
14 W. R. Buckheit, V. Fliaka-Boltz, D. W. Decker, L. J.
Roberson, C. A. Pyle, L. E. White, B. J. Bowden, J. H. Barth
and T. K. Antonucci, Antiviral Res., 1994, 25, 43.
Conflicts of interest
There are no conflicts to declare.
15 E. M. Arranz, J. A. Diaz, S. T. Ingate, M. Witvrouw, C.
Pannecouque, J. Balzarini, E. D. Clercq and S.Vega, Bioorg.
Med. Chem., 1999, 7, 2811.
Acknowledgments
We thank the Department of Science and Technology (DST, New
Delhi) for J C Bose fellowship and equipment [FIST and PURSE-Phase
2 programs], and the University Grants Commission (UGC, New
Delhi) under UPE program (also for equipment). S. K. and A.S.R
thanks UGC (New Delhi) for a fellowship and Dr. K. Selvaraj for
technical help.
16 J. K. Wales, S. V. Krees, A. M. Grant, J. K. Vikroa and F. W.
Wolff, J. Pharm. Exp. Ther., 1968, 164, 421.
17 X. Y. Liu, C. H. Li and C. M. Che, Org. Lett., 2006, 8, 2707.
18 T. Miura, M. Yamauchi, A. Kosaka and M. Murakami,
Angew. Chem., Int. Ed., 2010, 49, 4955.
19 S. Debnath and S. Mondal, J. Org. Chem., 2015, 80, 3940.
20 M. V. Pham, B. Ye and N. Cramer, Angew. Chem., Int. Ed.,
2012, 51, 10610.
21 (a) T. Lan, L. Wang and Y. Rao, Org. Lett. 2017, 19, 972; (b)
N. Thrimurtulu, R. Nallagonda and C. M. R. Volla, Chem.
Commun., 2017, 53, 1872.
22 X. Guo, L. Wang, J. Hu and M. Zhang, RSC Adv., 2018, 8,
22259.
23 S. Murru, P. Mondal, R. Yella and B. K. Patel, Eur. J. Org.
Chem., 2009, 31, 5406.
24 A. Siva Reddy and K. C. Kumara Swamy, Org. Lett., 2015,
17, 2996.
Notes and references
1
(a) P. Mujumdar and S. –A. Poulsen, J. Nat. Prod., 2015,
78, 1470; (b) P. Mujumdar, K. Teruya, K. F. Tonissen, D.
Vullo, C. T. Supuran, T. S. Peat and S. -A. Poulsen, J. Med.
Chem., 2016, 59, 5462.
2
M. Sadeghzadeh, S. Sheibani, M. Ghandi, F. J. Daha, M.
Amanlou, M. Arjmand and A. H. Bozcheloie, Eur. J. Med.
Chem., 2013, 64, 488-497.
25 Q. Liao, X. Yang and C. Xi, J. Org. Chem., 2014, 79, 8507.
26 (a) T. Mizuhara, S. Oishi, N. Fujii and H. Ohno, J. Org.
Chem., 2010, 75, 265; (b) G. Shen, X. Lv and W. Bao, Eur. J.
Org. Chem., 2009, 34, 5897; (c) Q. Ding, X. He and J. Wu, J.
Comb. Chem., 2009, 11, 587; (d) J.-W. Qiu, X.-G. Zhang, R.-
Y. Tang, P. Zhong, J.-H. Li, Adv. Synth. Catal. 2009, 351,
2319; (e) Y. -J. Guo, R.-Y. Tang, P. Zhong, J.-H. Li,
Tetrahedron Lett. 2010, 51, 649; (f) Q. Ding, B. Cao, X. Liu,
Z. Zong, Y.-Y. Peng, Green Chem. 2010, 12, 1607; (g) J.
Yang, P. Li and L. Wang, Tetrahedron 2011, 67, 5543; (h)
R. Wang, Z. Chen, L. Yue, W. Pan and J. -J. Zhao,
Tetrahedron Lett., 2012, 53, 4529; (i) W. Zhang, Y. Yue, L.
Song, Y. -Y. Xu, Y. -J. Tian and Y. -J. Guo, Adv. Synth. Catal.,
2012, 354, 2283.
3
4
C. Gennari, B. Salom, D. Potenza and A. Williams, Angew.
Chem., Int. Ed., 1994, 33, 2067.
K. G. Carson, C. F. Schwender, H. N. Shroff, N. A. Cochran,
D. L. Gallant and M. J. Briskin, Bioorg. Med. Chem. Lett.,
1997, 7, 711.
W. R. Roush, S. L. Gwaltney II, J. Cheng, K. A. Scheidt, J. H.
McKerrow and E. Hansell, J. Am. Chem. Soc., 1998, 120,
10994.
N. P. Lad, S. Kulkarni, R. Sharma, M. Mascarenhas, M. R.
Kulkarni and S. S. Pandit, Eur. J. Med. Chem., 2017, 126,
870.
5
6
7
8
J. Drews, Science 2000, 287, 1960.
(a) A. Mustafa, Chem. Rev., 1954, 54, 195; (b) G. J. Wells,
M. Tao, K. A. Josef and R. Bihovsky, J. Med. Chem., 2001,
44, 3488; (c) R. Bihovsky, M. Tao, J. P. Mallamo and G. J.
Wells, Bioorg. Med. Chem. Lett., 2004, 14, 1035; (d) P.
Francotte, P. Tullio, E. Goffin, G. Dintilhac, E. Graindorge,
27 (a) D. Ma, X. Lu, L. Shi, H. Zhang, Y. Jiang and X. Liu,
Angew. Chem., Int. Ed., 2011, 50, 1118; (b) L. Shi, X. Liu, H.
Zhang, Y. Jiang and D. Ma, J. Org. Chem., 2011, 76, 4200.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 13
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 14 of 14
ARTICLE
Journal Name
28 (a) F. Wang, S Cai, Q. Liao and C. Xi, J. Org. Chem., 2011,
View Article Online
76, 3174; (b) F. Wang, P. Zhao and C. Xi, Tetrahedron Lett.,
2011, 52, 231; (c) L. -R. Wen, Q. -Y. Shen, W. -S Guo and
M. Li, Org. Chem. Front., 2016, 3, 870; (d) L. -R. Wen, Q.
Dou, Y. -C. Wang, J. -W. Zhang, W. -S. Guo, and M. Li, J.
Org. Chem., 2017, 82, 1428; (e) L. -R. Wen, C. -C Zhou, M. -
Z. Zhu, S. -G. Xie, W. -S. Guo and M. Li, Org. Biomol.
Chem., 2019, 17, 3356.
DOI: 10.1039/C9OB00994A
29 A. Siva Reddy, A. L. Siva Kumari and K. C. Kumara Swamy,
Adv. Synth. Catal., 2016, 358, 1625.
30 M. Anitha and K. C. Kumara Swamy, Org. Biomol. Chem.,
2018, 16, 402.
31 In one case, some minor differences were observed. See:
L. Zirngibl and S. W. Tam, Helvetica Chim. Acta 1970, 53,
1927.
32 (a) S. L. MacNeil, O. B. Familoni and V. Snieckus, J. Org.
Chem., 2001, 66, 3662; (b) M. N. Reddy and K. C. Kumara
Swamy, Synthesis 2014, 46, 1091.
33 However, some very interesting reactions using
isothiocyanates have been recently reported. See, for
example: (a) M. Sengoden, R. Irie, T. Punniyamurthy, J.
Org. Chem., 2016, 81, 11508; (b) A. Modi, W. Ali, B. K.
Patel, Org. Lett., 2017, 19, 432.
34 D. K. Barange, V. R. Batchu, D. Gorja, V. R. Pattabiraman,
L. K. Tatini, J. M. Babu and M. Pal, Tetrahedron 2007, 63,
1775.
35 (a) H. Xu and H. Fu, Chem. Eur. J., 2012, 18, 1180; (b) K.
Kundu, K. Mitra and A. Majee, RSC Adv., 2015, 5, 13220;
(c) X. Pang, C. Chen, M. Li and C. Xi, Beilstein J. Org.
Chem., 2015, 11, 2365; (d) M. Kuil, L. Bekedam, G. M.
Visser, A. van den Hoogenband, J. W. Terpstra, P. C. J.
Kamer, P. W. N. M. van Leeuwen and G. P. F. van
Strijdonck, Tetrahedron Lett., 2005, 46, 2405.
36 W. Ding, S. Mai and Q. Song, Beilstein J. Org. Chem., 2015,
11, 2158.
37 The benzylic α-site is perhaps more reactive than the
remaining β-site for iodination and hence the minor
isomer has iodine at the β-site. The assignment of the
structure to the minor isomer is primarily based on the 1H
NMR peak observed at δ 8.50; this peak could be readily
seen in the 1H NMR spectrum recorded for the single
crystal for which the X-ray data was collected.
38 I. Handke, E. Schaumann and R. Ketcham, J. Org. Chem.,
1988, 53, 5298.
39 This is a known compound. See: R. Anana, P. N. P. Rao, Q.
-H. Chenb and E. E. Knaus, Bioorg. Med. Chem., 2006, 14,
5259.
40 See, for example: (a) S. Bhunia, G. G. Pawar, S. Vijay
Kumar, Y. Jiang and D. Ma, Angew. Chem., Int. Ed., 2017,
56, 16136; (b) H. -J. Cristau, A. Ouali, J. -F Spindler and M.
Taillefer, Chem. Eur. J., 2005, 11, 2483; (c) A. Klapars, X.
Huang and S. L. Buchwald, J. Am. Chem. Soc., 2002, 124,
7421; (d) J. Zhao, S. Niu, X. Jiang, Y. Jiang, X. Zhang, T. Sun
and D. Ma, J. Org. Chem., 2018, 83, 6589.
41 W. L. F. Armarego, D. D. Perrin and D. R. Perrin,
Purification
of
Laboratory
Chemicals.
Oxford:
Butterworth-Heinemann, 4th Edition, 1996.
42 K. C. Majumdar, S. Mondal, N. De, Synthesis 2009, 18,
3127.
43 M. J. Zenner, R. C. Larock,. J. Org. Chem., 1999, 64, 7312.
14 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins