Base induced synthesis of 4H-1,4-benzothiazines and their computational studies

Article abstract of DOI:10.1039/c5ra12442e

A one pot synthesis of 1,4-benzothiazines from 1,3-benzothiazolium cations and α-haloketones through ring expansion under ultrasonication was carried out by employing optimal 5% sodium hydroxide and characterization was done with the help of various spectroscopic techniques viz. NMR, IR and mass spectrometry. Single crystal X-ray diffraction and computational studies of (4-bromophenyl)(4-methyl-4H-benzo[b][1,4]thiazin-2-yl)methanone (3c) were also performed. Different concentrations of different bases (NaOH, Na₂CO₃, NaHCO₃ solutions etc.) were used to obtain 1,4-benzothiazine derivatives. But, the best results were obtained with 5% NaOH solution (3.7 equivalents) for the synthesis of single product 1,4-benzothiazine derivatives while, with other concentrations, the reaction did not proceed to a single product. Quantum chemical calculations were done to find the optimized geometry and to correlate the experimental and calculated values of the bond parametres and ¹³C NMR chemical shifts of the synthesized compound. The optimized geometry was obtained using density functional theory (DFT) with the basis set 6-31G(d). The theoretical values of the ¹H NMR chemical shifts were in agreement with the experimental values. The photophysical properties of some of the synthesized compounds were studied with the help of ultraviolet-visible and fluorescence spectroscopy.

Full text of DOI:10.1039/c5ra12442e

View Article Online
View Journal
RSC Advances
This article can be cited before page numbers have been issued, to do this please use: S. preet and D. S.
Cannoo, RSC Adv., 2015, DOI: 10.1039/C5RA12442E.
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Accepted Manuscripts are published online shortly after
acceptance, 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. This Accepted Manuscript will be replaced by the edited,
formatted and paginated article as soon as this 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 shall the Royal Society of Chemistry be held
responsible for any errors or omissions in this Accepted Manuscript
or any consequences arising from the use of any information it
contains.
www.rsc.org/advances

Page 1 of 21
RSC Advances
View Article Online
DOI: 10.1039/C5RA12442E
Graphical Abstract
CH
3
N
H
CH
N+
3
S
CO
BrCH COAr-X
2
I-
S
X
Monoclinic

RSC Advances
Page 2 of 21
View Article Online
DOI: 10.1039/C5RA12442E
1
2
Base induced synthesis of 4H-1,4-benzothiazines and their computational
studies
1
1*
3
4
5
6
Simer Preet , Damanjt Singh Cannoo
1*
Department of Chemistry, Sant Longowal Institute of Engineering and Technology, Longowal - 148106,
Distt. Sangrur (Pb.), India. E-mail: djs6311@gmail.com
Fax: 91-1672-280072; Tel: 91-1672-253200 (O)
7
8
Abstract
9
0
1
2
3
4
5
6
7
8
A one pot synthesis of 1,4-benzothiazines from 1,3-benzothiazolium cations and α-haloketones through ring expansion under ultrasonication
was carried out by employing optimized 5% sodium hydroxide and the characterization was done with the help of various spectroscopic
techniques viz. NMR, IR and Mass Spectrometry. Single crystal X-Ray diffraction and computational study of (4-Bromophenyl)(4-methyl-4H-
1
1
1
1
1
1
1
1
1
2 3 3
benzo[b][1,4]thiazin-2-yl)methanone (3c) was also studied. Different concentartion of different bases ( NaOH, Na CO , NaHCO solutions etc.)
were used to get 1,4-benzothiazine derivatives. But, the best results were obtained with 5% NaoH solution (3.7 equivalent) for thesynthesis of
single product 1,4-benzothiazine derivatives while, with other concentration, reaction has not proceed to single product. Quantum chemical
13
calculations was done to find the optimized geometry and to correlate the experimental and calculated values of bond parametres and C NMR
chemical shifts of the synthesized compound. The optimized geometry was obtained by density functional theory (DFT) with the basis set 6-
1
31G (d). The theoretical values of H NMR chemical shifts were in consonant with the experimental values. The photophysical properties of
some of the synthesized compounds was done with the help of ultraviolet-visible and flourescence spectroscopy.
1
9
Keywords: benzothiazole, α-haloketone, one pot, ultrasonication
2
2
2
2
2
2
2
2
2
2
0
1
2
3
4
5
6
7
8
9

Page 3 of 21
RSC Advances
View Article Online
DOI: 10.1039/C5RA12442E
3
3
0
1
1. Introduction
1
3
3
3
3
2
3
4
5
Heterocyles having more than one heteroatom have been in the focus due to their multifarious biological activities. Amongst
these, the six membered heterocycles especially 1,4-benzothiazines, owing to the presence of nitrogen, carbon and sulfur
linkage have attained an important place due to their wide range of applications in different fields like pharmaceutical,
2
medicinal, therapeutic, agricultural etc. 1,4-benzothiazine derivatives possess numerous biological activities viz. antibiotic,
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
anticancer, antiviral, antifungal, antimicrobial, and antiparkinson, anti inflammatory, antihypertensive, anti tumor, anti aldoso
3-7
reductase, anti rheumatic, anti arrhythmic, anti HIV anti allergic etc. Even some of these moieties have been known to be
8
better antipyretics and analgesics in comparison with aspirin. A well known anti-psychotic drug, phenothiazine comprises of
9
benzothiazine core nucleus. It has been reported that a slight change in the substituents of 1,4-benzothiazine derivatives can
9
cause a significant change in their activities.
In view of above, various synthetic methodologies have been developed to synthesize 1,4-benzothiazines and their
4,5,10
derivatives viz. cyclocondensations and fewer ring transformations.
The most general one involves cyclocondensation of 2-
aminobenzothiazole with α,β-unsaturated acids or esters, electron deficient alkynes; cyclocondensations of 2-
aminobenzothiaoles with α-haloketones; condensation and oxidative cylization of N-unsubstituted and N,N-dialkyldithioanilines
with 1,3-dicarbonyls or esters; ring expansions of benzothiazolines by using different oxidants like iodine and sulfuryl chloride
4
,10
to synthesize 1,4-benzothiazine and their derivatives.
Even, ring contractions of benzothiazepinones were also reported in
4
the literature for the synthesis of above said moieties. The present finding belongs to ring expansion category by greener
method i.e ultrasonication. Ultrasonication has been an advantageous finding in the synthetic world especially in case of
reactions which require harsh reaction conditions and prolonged/long reaction time. Ultrasonication has been an enabling key
advantage over conventional procedure and taken up organic synthesis to a reliable, sophisticated and level headed pathway
with reduction in temperature and reaction time, higher yields, selectivity and reproducibility, optimization, avoids toxicity,
2,3,4,5,6,9,11,12,13,14,15
reduce multistep reactions to single step, less byproducts.
The present paper discussses the synthesis of 1,4-benzothiazine derivatives using a greener synthetic pathway i.e
ultrasonication method and their characterization by NMR, IR, UV-Vis, Flourescence and Mass Spectrometry. Also, single crystal
1
13
X-ray diffraction and computational study was done. H and C NMR is a basic tool for the structural elucidation of any organic
molecule. So, experimental and calculated chemical shifts obtained are correlated to confirm the structure of the compound 3
(c).
5
8
2. Computational study

RSC Advances
Page 4 of 21
View Article Online
DOI: 10.1039/C5RA12442E
1
13
16
5
6
6
6
6
6
6
6
6
6
6
7
7
7
7
7
7
7
7
7
7
8
8
8
8
8
8
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
The optimized molecular geometry, H and C NMR calculations were performed with the Gaussian 09W by DFT methods
with B3LYP (Beck three parameter Lee-Yang-Parr) exchange correlation functional, which combines the hybrid exchange
1
7
18
functional of Becke , with the gradient- correlation functional of Lee et al. The 6-31G (d) basis set was used for calculation in
1
13
the gas phase of the structure 3 (c). The optimized geometry with the 6-31G (d) basis set was used in the H and C NMR
calculations in the DFT to characterize all stationary points as minima. The calculated geometrical parameters viz. Bond lengths
and bond angles were compared with the experimental geometrical parameters obtained from single crystal X-ray data of
compound 3 (c). The optimized structural parameters using B3LYP/6-31G(d) are listed in Table 1 along with an optimized
structure with atom number in Figure 1. Table 1 shows that optimized parameters were in good agreement with X-ray crystal
structure. The optimized bond length of C (11) -S and C (9) -N is 1.796 Å and 1.368 Å respectively. However, actual bond
lengths of C (11) -S and C (9) -N is 1.773 Å and 1.361 Å. The optimized bond angles for C (9) -N(1) -C(10) and C (7) –C (8) -S(1)
are 123.1° and 118.2° respectively. Whereas actual bond angles are 123.1° and 114.4°. The largest difference between
calculated and experimental bond lengths and bond angles are about -0.04 Å at S (1) –C (8) and -3.8° in C (7) –C (8) –S (1)
respectively. The slight deviation in single crystal X-ray data and the computed geometrical data is due to the fact that crystal
packing interactions in the solid state are dominant in comparison with optimized geometry of a molecule in the gas phase.
1
9-22
Shielding tensors of structure of compound 3 (c) were computed within the GIAO approach
. By applying the
similar methods and 6-31G(d) basic set used for geometrical optimization. It is pertinent to optimize the geometry of TMS and
1
13
chloroform molecule in order to express the chemical shift in ppm. H and C NMR spectra were calculated by 6-31G (d) basis
set for structure of compound 3 (c). The equation, δi = σTMS – σi have been used to convert the calculated isotropic shielding
1
13
constants σi to chemical shifts relative to TMS. Experimental and calculated H and C NMR chemical shifts (ppm) of compound
1
3(c) has been enlisted in Table 2. Only a single value for hydrogen atoms of CH groups is available in experimental H NMR. So,
3
1
the average of calculated H NMR chemical shift values was used.
1
In H NMR of compound 3 (c), singlet of =C-H comes at δ= 13.1556 in comparison to experimental value which comes
at δ= 6.5332. The average calculated chemical shift of N-CH protons comes at 3.5888 ppm whereas experimental chemical
3
13
shifts was 3.07 ppm.The calculated C=O chemical shifts in C NMR spectra comes at 165.9 whereas in experimental spectra the
13
peak is at 187.5 ppm. Carbon attached to the nitrogen atom in experimental and calculated C NMR give peaks at 36.2ppm and
1
3
52.6 ppm respectively.The correlation values of calculated and experimental calculated C NMR chemical shifts were found to
13
be 0.995 (Figure 2). Experimental C NMR chemical shifts show good correlation which confirms the structure of compound 3
(c). The opꢀmized structure of compound 3 (c) didn΄t show any negaꢀve frequency in the frequency opꢀmized calculaꢀon

Page 5 of 21
RSC Advances
View Article Online
DOI: 10.1039/C5RA12442E
8
8
7
8
which automatically confirms that global minimum or equillibrium geometry has been found. The calculated energy of
optimized structure of compound 3 (c) is -3716.03 a.u. and the dipole moment was 5.63 debye with the point group C1.
8
9
3. Result and discussion
9
9
9
9
9
9
9
9
9
9
0
1
2
3
4
5
6
7
8
9
Numerous cyclocondensations have been reported for the synthesis of 4H-1,4-benzothiazines by multistep procedures and
rigorous reaction conditions. The present study involves one pot synthesis of 4H-1,4-benzothiazines from ionic liquid based N-
methyl-1,3-benzothiazolium iodide or N-methyl-6-nitro-1,3-benzothiazolium iodide [prepared from 1,3-benzothiazole or 6-
nitro-1,3-benzothiazole and methyl iodide (Scheme in supplementary data)] and the derivatives of phenacyl bromide in basic
1
13
medium (Scheme 1). The structure of the synthesized 4H-1,4-benzothiazines were established through spectral data ( H, C
1
NMR, Mass, IR). The singlet in H NMR of the products at δ 6.53 confirms the hydrolytic cleavage of C-S and alternate cyclization
to 1,4-benzothiazine ring. The singlet due to three protons between δ 3- 4 shows N-CH in the species, (additional singlets at δ
3
3.8 (3H), δ 2.3 (3H), δ 2.51 (3H) in 3 (d), 3 (e) and 3 (h) due to methoxy and methyl group, respectively), whereas the multiplet
1
3
between δ 6-8 confirms the presence of two phenyl rings in the product. The peak in C NMR between δ 180-190 ppm [3(b), 3
1
13
+
(d), 3 (g)] shows the presence of C=O in the compounds. Besides above the peaks in H and C NMR, the M in Mass
+
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
00
01
02
03
04
05
06
07
08
09
10
11
12
13
14
15
Spectrometry corresponds to the molecular weight of the compounds, however 3 (b) and 3 (c) show M , m/z at 302.1; 304.1
+
(3:1) and 346.1; 348.1 (1:1) which indicates the presence of chlorine and bromine in the said compounds. Similarly, M , m/z at
313 and 327 confirms compound 3(f) and 3 (h), respectively. Lastly, the structure of 3 (c) was confirmed on the basis of single X-
ray diffraction and DFT studies (discussed above ). To validate the structure, analytical and calculated results were correlated
and the values were in good accordance with each other which confirm the structure of compound 3 (c).
The reaction of N-methyl benzothiazolium iodide or N-methyl-6-nitro-1,3-benzothiazolium iodide and the α-haloketone
was carried out with different concentrations of bases (sodium hydroxide, sodium carbonate etc.). The optimum concentration
of NaOH being 5% (3.7 equivalent) which provided 1,4-benzothiazines. It has been observed that at higher concentrations of
the base the product decomposed whereas, at lower concentration the reaction didnot proceed to completion. The reaction
was carried out by both conventional and greener routes ( comparison Table in supplementary data). Employing the latter, i.e.
through ultrasonication the yield of the product enhanced and a substantial reduction in reaction time was observed. In
conventional route, not only the reaction time was more and yields were less but also, the use of solvent was N,N-
dimethylformamide while in ultrasonication ecofriendly solvent methanol has been used.
The reaction could be envisaged to proceed through the initial nucleophilic attack of the hydroxide ion at C(2) of N-
methyl benzothiazolium iodide or N-methyl-6-nitro-1,3-benzothiazolium iodide to form a pseudobase 2(a) which could undergo
hydrolytic C (2) -S cleavage to give 2 (b) that further reacts with phenacyl bromide to form 2(c). The latter, under the reaction

RSC Advances
Page 6 of 21
View Article Online
DOI: 10.1039/C5RA12442E
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
conditions is visualised to generate α-thiocarbanion 2 (d) which finally undergoes intramolecular cyclisation along with removal
of H O to give the target molecule 3 (Scheme 2).
2
2.1. Single crystal X-ray diffraction study and structural description
X-ray diffraction study was done on X Calibur EOS OXFORD Diffractometer at 293 (2) K. The structure was solved by SHELX-97
23
software package. The non-hydrogen atoms were refined with anisotropic parameters. Compound 3 (c) crystallizes in the
monoclinic system with the refinement of 0.0587. The crystal have space group P21/n and cell formula units was 4. The cell
length of the crystal a, b, c are 11.7172 (19) 9.2242 (17) 13.153 (2) respectively, and angles were α= 90, β= 93.150 (16) and ϒ=
90. The graphite monochromator radiation with type Moka with wavelength of 0.71073 was used for diffraction study. The
2
bond angle of O1-C7-C8 is 118.7° (4) shows that C7 is sp hybridized and the bond length of O1-C7 is 1.243 (7) Å depicts its
double bond character. Similarly the bond length of C9-C-8 is 1.345 (6) Å also reveals that they have a double bond between
them. The ortep diagram of compound 3 (c) [(4-Bromophenyl)(4-methyl-4H-benzo[b][1,4]thiazin-2-yl)methanone] shown in
Figure 3 along with crystal close packing along a, b, c coordinates ( Figure in supplementary data) and the structural data was
given in Table 3.
2.2. Absorption Spectra
The absorption spectra of compounds 3 (c), 3 (d), 3 (g) and 3 (i) was recorded in chloroform and DMSO and the spectrum has
been shown in Figure 4 and Figure 5. As spectra reveals that the maximum absorption in the above said compounds comes
between the range 180-200 and 290-300 owing to the presence of C=O in the compounds. This absorptions attributed to the π-
π* and n-π* transitions respectively. Another absorption peak comes in the range 390-460 due to benzothiazine chromophore.
Similar absorption peaks in the spectra indicate that all the compounds have similar structures. The presence of the nitro group
in compounds 3 (g) and 3 (i) shows increase in absorption spectra towards higher wavlength i.e there is presence of red shift.
2.3. Fluorescence
The emission spectra of compounds 3 (c), 3 (d), 3 (g) and 3 (i) have been shown in Figure 6, the emission and excited
wavelength are given in Table 4. The emission spectra of compounds 3 (c), 3 (d), 3 (g) and 3 (i) show peaks at 373 nm, 577nm,
421 nm, 321nm respectively. So, these compounds represent the single fluorescence emission band which makes these
compound fluorescence active. Spectrum of Figure 6 shows that compound 3 (c) and 3 (d) were more fluorescence active in
comparison to compound 3 (g) and 3 (i).
1
42
3. Experimental
1
1
43
44
All the chemicals and solvents were purchased from Sigma Aldrich and were used without further purification. Melting points of
the compounds were determined through the melting point apparatus. Ultrasonic bath (LINCO, Ambala) was used for

Page 7 of 21
RSC Advances
View Article Online
DOI: 10.1039/C5RA12442E
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
ultrasound waves having frequency 40MHz. Thin layer chromatography (TLC) was performed with glass plates coated with silica
1
13
gel G and were exposed to iodine vapors to check the progress of the reaction. H and C NMR spectra were run in CDCl on a
3
BRUKER ADVANCE II 400 NMR spectrophotometer instrument using tetramethylsilane (TMS) as an internal reference standard
and the values were given in ppm (δ). Mass spectra were recorded on Waters Q-T of Micromass (LC-MS) and Shimadzu GCMS-
QP 2010 gas chromatogram mass spectrometer. UV spectra were run on a UV-1800 (Shimadzu) and for Fluorescence, spectra
were recorded on RF-5301PC Spectrofluorophotometer (Shimadzu). Single crystal X-ray diffraction study was done on X Calibur
EOS OXFORD Diffractometer.
3.1. General procedure for the synthesis of N-methyl-1,3-benzothiazolium iodide or N-methyl-6-nitro-1,3-benzothiazolium
iodide (2): An equimolar mixture of 1,3-benzothiazole or 6-nitro-1,3-benzothiazole (1) (2.7038 g, 0.02mol, 1 equivalent) and
methyl iodide (1.245mL, 0.02mol, 1 equivalent) was subjected to ultrasonication under solvent free conditions for 4-5 hrs to
obtain light yellow colored solid. The solid thus obtained was washed with diethyl ether to remove unreacted material (yield:
24
95%). Lit.
3.2. Procedure for the synthesis of 1,4-benzothiazines (3).
Ultrasonication (green method): A mixture of N-methyl 1,3-benzothiazolium iodide or N-methyl-6-nitro-1,3-benzothiazolium
iodide (2) and α-haloketone and 5% NaOH solution (18 mL, 3.7 equivalent) in methanol under ultrasonication for 25-30 minutes
gives 1,4-benzothiazines in better yield. The solid, thus separated was filtered, washed with hexane and recyrstallized from
chloroform.
3.3. Under Phase transfer catalyst condition: A mixture of N-methyl 1,3-benzothiazolium iodide or N-methyl-6-nitro-1,3-
benzothiazolium iodide (2) and α-haloketone, 5% NaOH solution (18 mL, 3.7 equivalent) and tetrabutyl ammonium bromide
(PTC as catalyst) (0.1 mol) in methanol under ultrasonication for 15-20 minutes gives 1,4-benzothiazines in better yield (80-
85%). The product further washed and recrystallized as above mentioned procedure.
Spectral data of selected compounds:
o
-
3.3.1. (4-Methyl-4H-benzo[b][1,4]thiazin-2-yl)(phenyl)methanone (3a): Orange color solid; mp: 170 C; yield: 70%; υ= 1660 cm
1
1
(C=O); HNMR (CDCl , 400MHz): δ= 3.06 (s, 3H, N-CH ), 6.51-6.53 (d, 1H, -C H of benzothiazole ring, J= 8.0 Hz), 6.77 (s, 1H,
3
3
6 5
=CH), 6.83-6.88 (m, 2H, -C H of benzothiazole ring), 6.92-6.96 (m, 1H, -C H of benzothiazole ring), 7.39-7.43 (q, 2H, -C H of
6
5
6
5
6 5
benzene ring, J= 15.7 Hz, J= 6.9 Hz), 7.45-7.49 (m, 1H, -C H of benzene ring), 7.52-7.54 (t, 2H, -C H of benzene ring, J= 6.8 Hz);
6
5
6 5
+
m/z 267 (M ), 224, 162, 130, 105, 77, 69, 51, 50.
o
3.3.2. (4-Chlorophenyl)(4-methyl-4H-benzo[b][1,4]thiazin-2-yl)methanone (3b): Orange color solid; mp:190 C; yield: 72%;
1
HNMR (CDCl , 400MHz): δ= 3.08 (s, 3H, N-CH ), 6.53-6.55(d, 1H, -C H of benzothiazole ring, J= 8.0Hz), 6.74 (s, 1H, =CH), 6.86-
3
3
6 5

RSC Advances
Page 8 of 21
View Article Online
DOI: 10.1039/C5RA12442E
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
2
2
2
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
00
01
02
6.87 (d, 2H, -C H of benzothiazole ring, J= 4.2 Hz), 6.93-6.97 (m, 1H, -C H of benzothiazole ring, 7.38-7.40 (d, 2H, -C H of
6 5 6 5 6 5
13
benzene ring, J= 8.2 Hz), 7-47-7.50 (d, 2H, -C H of benzene ring, J= 8.3 Hz); C NMR (100MHz, CDCl ): δ 186.9 (C=O), 149.3,
6
5
3
+
139.0, 137.0, 131.5, 129.9, 127.5, 127.2, 125.8, 125.3, 122.2, 113.3, 106.7 (C H ), 40.4 (=CH-); m/z 301.1 (M+H ) (100%).
6
5
o
1
3.3.3. (4-Bromophenyl)(4-methyl-4H-benzo[b][1,4]thiazin-2-yl)methanone (3c): Orange color solid; mp: 175 C; yield: 75%; H
NMR (CDCl , 400MHz): δ= 3.07 (s, 3H, N-CH ), 6.52-6.54 (d, 1H, -C H of benzothiazole ring, J= 8.0 Hz), 6.73 (s, 1H, =CH), 6.85-
3
3
6 5
6.86 (m, 2H, -C H of benzothiazole ring), 6.92-6.96 (m, 1H, -C H of benzothiazole ring), 7.40-7.42 (m, 2H, -C H of benzene
6
5
6
5
6 5
+
ring), 7.53-7.56 (m, 2H, -C H of benzene ring); m/z 346; 348 (1:1) (M+H ) (100%).
6
5
o
3.3.4. (4-Methoxyphenyl)(4-methyl-4H-benzo[b][1,4]thiazin-2-yl)methanone (3d): Orange color solid; mp:168 C; yield: 72%;
1
HNMR (CDCl , 400MHz): δ= 3.07 (s, 3H, N-CH ), 3.85 (s, 3H, -OCH ), 6.51-6.53 (d, 1H, -C H of benzothiazole ring, J= 7.9 Hz),
3
3
3
6 5
6.80 (s, 1H, =CH-), 6.84-6.90 (m, 2H, -C H of benzene ring), 6.92-6.96 (m, 3H, -C H of benzothiazole ring), 7.53-7.57 (m, 2H, -
6
5
6 5
1
3
C H of benzene ring); C NMR (100MHz, CDCl ): δ 187.3 (C=O), 161.9, 148.8, 139.6, 130.6, 130.4, 127.5, 127.1, 125.5, 122.4,
6
5
3
113.6, 113.0, 106.9 (C H ), 55.4 ( -C-OCH ), 40.2 (=CH-); m/z 297 (M+), 254, 162, 135, 107, 92, 77, 64.
6
5
3
o
3.3.5. (4-Methylphenyl)(4-methyl-4H-benzo[b][1,4]thiazin-2-yl)methanone (3e): Light orange yellow color solid; m.p:168 C;
1
yield: 78%; HNMR (CDCl , 400MHz): δ= 2.39 (s, 3H, -CH ), 3.0 (s, 3H, N-CH ), 6.51-6.53(d, 1H, -C H of benzothiazole ring, J= 8.0
3
3
3
6 5
Hz), 6.79 (s, 1H,=CH-), 6.84-6.87 (t, 2H, -C H of benzothiazole ring, J= 5.0 Hz), 6.91-6.96 (m, 1H, -C H of benzothiazole ring),
6
5
6 5
7.20-7.26 (t, 2H, -C H of benzene ring, J= 15.7 Hz), 7.44-7.46 (d, 2H, J= 7.9 Hz, -C H of benzene ring); m/z 281 (M+), 236, 162,
6
5
6 5
119, 91, 77, 65, 39.
o
3.3.6. (4-Methyl-7-nitro-4H-benzo[b][1,4]thiazin-2-yl)(phenyl)methanone (3f): dark purple color solid; m.p: 290 C; yield: 76%;
1
HNMR (CDCl , 400MHz): δ= 3.68 (s, 3H, N-CH ), 6.84-6.86 (d, 1H, -C H of benzothiazole ring, J= 9.0 Hz), 7.01 (s, 1H,=CH-), 7.66-
3
3
6 5
7.67 (d, 1H, -C H of benzothiazole ring, J= 2.6 Hz), 7.83-7.86 (q, 1H, -C H of benzothiazole ring, J= 11.6 Hz, J= 6.3 Hz), 7.56-7.61
6
5
6 5
+
(m, 3H, -C H of benzene ring, 7.47-7.51 (m, 2H, -C H of benzene ring); m/z 313 (M+H ).
6
5
6 5
o
3.3.7. (4-chlorophenyl)(4-Methyl-7-nitro-4H-benzo[b][1,4]thiazin-2-yl)methanone (3g): dark purple color solid; m.p: 293 C;
-
1
-1
-1
-1
-1
1
yield: 78%; υ= 1781 cm (C=O); 1598 cm , 1366 cm (NO ); 3068 cm (=C-H stretching); 743.23 cm (=C-H bending); HNMR
2
(CDCl , 400MHz): δ= 3.14 (s, 3H, N-CH ), 6.84-6.86 (d, 1H, -C H of benzothiazole ring, J= 9.0 Hz), 7.05 (s, 1H,=CH-), 7.53-7.55 (q,
3
3
6 5
2H, -C H of benzothiazole ring, J= 8.5 Hz, J= 4.7 Hz), 7.61-7.66 (m, 3H, -C H of benzene ring, 7.83-7.86 (q, 1H, -C H of benzene
6
5
6
5
6 5
13
ring, J= 11.6 Hz, J= 6.4 Hz ); C NMR (100MHz, CDCl ): δ 186.0 (C=O), 149.6, 145.2, 143.9, 130.3, 128.5, 124.09, 123.57, 121.13,
3
113.89(C H ), 40.08 (=CH-); m/z 346 (M+), 316, 301, 177, 161, 141, 139, 113, 111.
6
5
o
3.3.8. (4-bromophenyl)(4-methyl-7-nitro-4H-benzo[b][1,4]thiazin-2-yl) methanone (3h): dark purple color solid; m.p: 295 C;
1
yield: 82%; HNMR (CDCl , 400MHz): δ= 3.10 (s, 3H, N-CH ), 6.50-6.52 (d, 1H, -C H of benzothiazine ring, J= 8.00 Hz), 6.64 (s,
3
3
6 5

Page 9 of 21
RSC Advances
View Article Online
DOI: 10.1039/C5RA12442E
2
2
2
2
2
2
2
2
03
04
05
06
07
08
09
10
1H,=CH-), 7.43-7.45 (q, 2H, -C H of benzene ring, J= 8.44 Hz, J= 4.84 Hz), 7.57-7.60 (q, 2H, -C H of benzene ring, J= 8.44 Hz, J=
6 5 6 5
4.80 Hz), 7.65-7.66 (d, 1H, -C H of benzothiazine ring, J= 2.52 Hz), 7.79-7.82 (q, 1H, -C H of benzothiazine ring, J= 11.44 Hz, J=
6
5
6 5
6.32 Hz); m/z 390 (M+), 346, 222, 185, 155, 134, 104, 76.
o
3.3.9. (4-Methyl-7-nitro-4H-benzo[b][1,4]thiazin-2-yl)(p-tolyl)methanone (3i): dark purple color solid; m.p: 297 C; yield: 80%;
1
HNMR (CDCl , 400MHz): δ= 2.51 (s, 3H, -CH ), 3.36 (s, 3H, N-CH ), 6.83-6.85 (d, 1H, -C H of benzothiazole ring, J= 9.12 Hz),
3
3
3
6 5
7.01 (s, 1H,=CH-), 7.65-7.66 (d, 1H, -C H of benzothiazole ring, J= 2.60 Hz), 7.83-7.86 (q, 1H, -C H of benzothiazole ring, J=
6
5
6 5
11.60 Hz, J= 6.28 Hz), 7.50-7.52 (d, 2H, -C H of benzene ring, J=8.08 Hz), 7.28-7.30 (d, 2H, -C H of benzene ring, J= 7.88 Hz);
6
5
6 5
+
m/z 327 (M+H ), 226.
2
11
4. Conclusion
2
2
2
2
12
13
14
15
The synthesis of 1,4-benzothiazines through ultrasonication- a green methodology consumes less time and provide the target
molecules in better yields. Further, DFT study was carried out for compound 3(c). The experimental and theoretical values show
good correlation which supports the structure of compound 3(c). The flourescence spectra of compounds 3 (c), 3 (d), 3 (g) and 3
(i) reveals that that these compounds exhibit excellent flourescent activity.
2
16
Acknowledgement
2
2
17
18
The authors are highly acknowledged to Sant Longowal Institute of Engineering and Technology (SLIET), Longowal and Panjab
University (PU), Chandigarh for providing all the necessary facilities to carry out this research.
2
2
2
2
2
2
2
2
2
2
19
20
21
22
23
24
25
26
27
28

RSC Advances
Page 10 of 21
View Article Online
DOI: 10.1039/C5RA12442E
2
29
References
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
1
2
3
4
5
6
Z. Qiao, H. Liu, X. Xiao, Y. Fu, J. Wei and Y. Li, Org. Lett., 2013, 15, 2594–2597.
A.M.A. Souza, S.T.P. Walfrido, L.F.C. Leite, M.C.A. Lima and S.L.G. e I. R. Pitta, Quim. Nova., 2010, 33, 562-565.
N. Kumar and A.K. Yadav, Indian J. Chem., 2008, 47B, 748-752.
M.K. Parai and G. Panda, Tetrahedron Lett., 2009, 50, 4703–4705.
W.L. Li, S.B. Tian and F. Zhu, The Scientific World J., doi.org/10.1155/2013/838374.
M. SaadouniT. Ghailane, S. Boukhris, A. Hassikou, N. Habbadi, R. Ghailane, M. Harcharras, A. Souizi, H. Amri, Org.
Commun., 2014, 7, 77-84.
7
L.J. Meng, H. Zuo, Z.B. Li, G. Dupati, K. Jang, G. Moon, B.X. Zhao, J.Y. Miao and D.S. Shin, Res. Rep. Med. Chem., 2013,
3, 11–20.
8
9
D. Shahwar, U. Sana and N.Ahmad, Turk. J. Chem., 2013, 37, 262 – 270.
V.V. Dabholkar and R.P. Gavande, Arab. J. Chem., doi: 10.1016/j.arabjc.2011.03.009.
10 H.J. Pi, H. Liu, W. Du and W.P. Deng, Tetrahedron Lett., 2009, 50, 4529–4531.
11 N. Khandelwal, Abhilasha, N. Gautam and D.C. Gautam, J.Chem. Sci., 2013, 125, 85-93.
12 S. Aloui, I. Forsal, M. Sfaira, M. Ebn Touhami, M. Taleb, M. Filali Baba, M. Daoudi, Port. Electrochim. Acta, 2009, 27,
599-613.
13 R.V. Dengle, R.D. Ingle, S.P. Bondge, R.A. Mane, Indian J. Chem., 1999, 38B, 390-393.
14 E. Mabrouk, A. Elachqar, A. Alami, A. EL Hallaoui and S. EL Hajji, Orient. J. Chem., 2010, 26, 1249-1255.
15 R.N. Prasad and K. Tietje, Can.J.Chem., 1966, 44, 1247-1258.
16 M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman, G. Scalmani, V. Barone, B.
Mennucci, G.A. Petersson, H. Nakatsuji, M. Caricato, X. Li, H.P. Hratchian, A.F. Izmaylov, J. Bloino, G. Zheng, J.L.
Sonnenberg, M. Hada,M. Ehara,K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao,
H.Nakai,T. Vreven, J.A. Montgomery, Jr., J.E. Peralta, F. Ogliaro, M. Bearpark, J.J. Heyd, E. Brothers, K.N. Kudin, V.N.
Staroverov, R. Kobayashi, J. Normand, K. Raghavachari, A. Rendell, J.C. Burant, S.S. Iyengar, J. Tomasi, M. Cossi, N.
Rega, J.M. Millam, M. Klene, J.E. Knox, J.B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R.E. Stratmann, O.
Yazyev, A.J. Austin, R. Cammi, C. Pomelli, J.W. Ochterski, R.L. Martin, K. Morokuma, V.G. Zakrzewsi, G.A.Voth, P.
Salvador, J.J. Dannenberg, S. Dapprich, A.D. Daniels, O. Farkas, J.B. Foresman, J.V. Ortiz, J. Cioslowski, D.J. Fox,
GAUSSIAN 09, Revision, Gaussian, Inc., Wallingford CT, 2009
17 A.D. Becke, Phys. Rev. A., 1988, 38, 3098–3100.

Page 11 of 21
RSC Advances
View Article Online
DOI: 10.1039/C5RA12442E
2
2
2
2
2
2
2
2
2
2
58
59
60
61
62
63
64
65
66
67
18 C. Lee, W. Yang, R.G. Parr, Phys. Rev., 1988, 37, 785–789.
19 K. Wolinski, J.F. Hilton, P. Pulay, J. Am. Chem. Soc., 1990, 112, 8251–8260.
20 R. Ditchfield, Mol. Phys., 1974, 27, 789–807.
21 M. Kaupp, M. Bühl, V.G. Malkin (Eds.), Calculation of NMR and EPR Parameters: Theory and Applications, Wiley-VCH,
Weinheim, 2004.
22 W. Koch, M.C. Holthausen, A Chemist’s Guide to Density Functional Theory, Wiley-VCH, Weinheim, 2001.
23 G.M. Sheldrick, SHELXTL-97, Program for Refinement of Crystal Structure, University of Gottingen, Gottingen,
Germany, 1997.
24 S. Nadeem, M.A. Munawar, S. Ahmad, M. Smiglak, D.M. Drab, K.I. Malik, R. Amjad, C.M. Ashraf, R.D. Rogers,
ARKIVOC., 2010, vii, 19-37.
2
68
Supporting information
1
13
2
2
2
2
2
2
2
69
70
71
72
73
74
75
Spectral data of the synthesised compounds along with copies of H, C NMR, mass spectra and X-ray data has been given in
supplementary data (file attached along with the paper). Supplementary data for this paper can be accesed on publisher’s
website.
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94

RSC Advances
Page 12 of 21
View Article Online
DOI: 10.1039/C5RA12442E
2
95
Scheme 1. Synthesis of 1,4-benzothiazine derivatives (3)
CH
3
N
H
CH
N+
3
2
BrCH COAr-X
+
I-
R
S
CO
S
R
X
2
2
96
97
2
2
3
3
98
99
00
01
(2)
(3)
R= -H; -NO2
X= -H, -Cl, -Br, -OCH , -CH
3
3
3
3
02
03
Scheme 2. Mechanism for synthesis of 1,4-benzothiazine derivatives
CH3
CH3
CH3
H
N+
S
OH-
N
O
H
N
I-
OH
C
S
S-
2
(a)
2(b)
CH
3
CH3
CH3
O
O
N
O
N
N
BrCH COAr-X
2
OH-
C
H
C
H
C
-
H
SH
SCH COAr-X
2
SCH COAr-X
2
(d)
2
(c)
CH3
N
CH3
N
OH
H
H
H
CO
S
CO
S
X
3
X
3
3
04
05
3
06

Page 13 of 21
RSC Advances
View Article Online
DOI: 10.1039/C5RA12442E
Figure captions
Figure 1. Optimized structure of compound 3(c)
13
Figure 2. Plot of calculated vs. Experimental C NMR chemical shifts (ppm) of compound 3 (c)
Figure 3. Ortep diagram of structure 3 (c)
Figure 4. UV-Vis absorption spectra of compounds 3 (c), 3 (d), 3 (g) and 3 (i) taken in chloroform
Figure 5. UV-Vis absorption spectra of compounds 3 (c), 3 (d), 3 (g) and 3 (i) taken in DMSO
Figure 6. Emission spectra of compounds 3 (c), 3 (d), 3 (g) and 3 (i) taken in chloroform

RSC Advances
Page 14 of 21
View Article Online
DOI: 10.1039/C5RA12442E
Figure 1

Page 15 of 21
RSC Advances
View Article Online
DOI: 10.1039/C5RA12442E
2
1
1
1
1
1
00
80
60
40
20
00
B3LYP/6-31G (d)
R² = 0.995
80
60
40
20
0
0
20
40
60
80
100
120
140
160
180
13
Calculated C NMR Shifts (ppm)
Figure 2

RSC Advances
Page 16 of 21
View Article Online
DOI: 10.1039/C5RA12442E
Figure 3

Page 17 of 21
RSC Advances
View Article Online
DOI: 10.1039/C5RA12442E
2
1
1
1
1
1
0
0
0
0
0
.0
.8
.6
.4
.2
.0
.8
.6
.4
.2
.0
3 (c)
3
3
3
(d)
(g)
(i)
3
00
400
500
600
700
800
W avelength (nm)
Figure 4

RSC Advances
Page 18 of 21
View Article Online
DOI: 10.1039/C5RA12442E
.
3
3
3
3
(c)
(d)
(g)
(i)
2
.0
.8
.6
.4
.2
.0
.8
.6
.4
.2
.0
1
1
1
1
1
0
0
0
0
0
300
400
500
600
700
800
Wavelength(nm)
Figure 5

Page 19 of 21
RSC Advances
View Article Online
DOI: 10.1039/C5RA12442E
3(c)
3
3
(d)
(g)
100
90
80
70
60
50
40
30
20
10
0
3(i)
280
300
320
340
360
380
400
420
440
460
Wavelength (nm)
Figure 6

RSC Advances
Page 20 of 21
View Article Online
DOI: 10.1039/C5RA12442E
Table 1. Selected experimental and calculated bond parameters of compound 3(c)
Parameters
Compound 3 (c)
Experimental
Calculated
Bond lengths (Å)
Br-C(1)
S(1)-C(8)
S(1)-C(11)
O(1)-C(7)
N(1)-C(9)
N(1)-C(10)
N(1)-C(12)
C(2)-C(3)
1.901
1.770
1.773
1.243
1.361
1.429
1.464
1.378
1.389
1.370
1.881
1.729
1.795
1.208
1.367
1.405
1.470
1.394
1.394
1.394
C(11)-C(16)
C(5)-C(6)
Bond Angles (°)
C(8)-S(1)-C(11)
C(9)-N(1)-C(10)
C(9)-N(1)-C(12)
C(10)-N(1)-C(12)
C(9)-C(8)-S(1)
99.9
101.4
123.1
118.4
118.4
123.4
118.2
121.7
119.2
123.1
122.4
118.3
118.8
122.0
114.4
120.9
121.1
127.2
C(7)-C(8)-S(1)
C(11)-C(10)-N(1)
C(13)-C(10)-N(1)
C(8)-C(9)-N(1)
1
13
Table 2. Experimental and calculated H NMR nd Cchemical shifts of compound 3 (c)
Experimental NMR
3.07
Calculated NMR
3.58
-
N-CH3-
=
Ar-H
C-H-
6.73
7.08
13.15
7.32
-
-
N-C
C=O
36.2
187.5
128.7
52.6
165.9
128.7
Ar-C

Page 21 of 21
RSC Advances
View Article Online
DOI: 10.1039/C5RA12442E
Table 3. Crystal data and structural refinement of compound 3 (c)
Table1: Structural data of (4-Bromophenyl)(4-methyl-4H-benzo[b][1,4]thiazin-2-yl)methanone
CCDC No.
1050855
Empirical formula
Formula mss
Temperature (K)
Crystal system
Space group
a, b, c (Ȧ)
C H BrNOS
16 12
346.24
293
Monoclinic
P21/n
11.7172(19) 9.2242(17) 13.153(2)
α, β, ϒ (°)
90,
93.150(16), 90
3
Volume (Ȧ )
1419.5(4)
Z
4
Density (calc)/ gcm-3
Mu (MoKa) [ /mm ]
Crystal Size [mm]
Radiation [Angstrom]
Theta Min-Max [Deg]
Refinement (R, wR, S)
Final R indices [I > 2σ(I) ]
R indices (all data)
R(int)
1.620
3.0
0.13 x 0.18 x 0.24
MoKa 0.71073
3.3, 29.0
0.0587, 0.1384, 1.00
R = 0.0587, wR = 0.1130
1
2
R = 0.1214, wR = 0.1387
1
2
0.041
Reflection collected
Independent reflections
3220
1872
0.999
2
Goodness-of-fit on F
Table 4. maximum excitation and emission wavelength of compound 3(c), 3(d), 3(g), 3(i) in CHCl solvents
3
Compounds
CHCl3
λex
λem
3
3
3
3
(c)
(d)
(g)
(i)
268
373
577
421
321
457
291
296