Visible-Light-Mediated Synthesis of 4H-benzo[1,4]thiazin-2-amines and 3,4-Dihydroquinoxalin-2-amines: An Efficient and Metal Free Route to C–S, C–N Bond Formation

Article abstract of DOI:10.1007/s10562-018-2388-2

Abstract: An efficient and practical synthesis of benzothiazine by visible-light-mediated free radical reaction has been developed. This protocol provides a new, facile, eco-friendly strategy to construct benzothiazine and quinoxaline derivatives via form

Full text of DOI:10.1007/s10562-018-2388-2

Catalysis Letters
https://doi.org/10.1007/s10562-018-2388-2
Visible-Light-Mediated Synthesis of 4H-benzo[1,4]thiazin-2-amines
and 3,4-Dihydroquinoxalin-2-amines: An Efficient and Metal Free
Route to C–S, C–N Bond Formation
Neetu Yadav1,2 · Hozeyfa Sagir1,2 · Mohd. Danish Ansari1,2 · I. R. Siddiqui1,2
Received: 15 December 2017 / Accepted: 8 April 2018
© Springer Science+Business Media, LLC, part of Springer Nature 2018
Abstract
An efficient and practical synthesis of benzothiazine by visible-light-mediated free radical reaction has been developed. This
protocol provides a new, facile, eco-friendly strategy to construct benzothiazine and quinoxaline derivatives via formation
of C–S and C–N bonds under metal-free condition. This synthesis has been performed under visible light illumination in
aqueous ethanol at room temperature using aromatic aldehyde, o-aminothiophenol and isocyanide as reactants.
Graphical Abstract
Keywords Visible-light · Metal-free · Eco-sustainable · Benzo[1,4]thiazin-2-amine
1 Introduction
of the natural products, biologically relevant compounds
and other functional materials (Fig. 1) [4–6]. Studies have
disclosed that many sulphur-containing heterocycles exhibit
excellent biological activities such as anticataract [7], vaso-
dilator [8], antidiabetic [9] and anti-arrhythmic activities
[10].
Heterocyclic compounds containing C–S (N) bonds display
important biological and chemical properties and afford
utility in various fields, including medicinal chemistry,
agrochemistry and organic synthesis [1–3]. Among them
1,4-benzothiazine derivatives have gained considerable
attention in organic synthesis as they are present in most
As a consequence, a number of new synthetic protocols
for construction of 1,4-benzothiazines rely using transi-
tion metal-catalysed reactions have been well developed
[11–14]. However, high cost, potential toxicity and their
limited availability in the future remain impediments of
these metal-based methods [15, 16]. Therefore, in light of
the importance of these compounds development of novel
and efficient methods to construct 1,4-benzothiazine
* I. R. Siddiqui
dr.irsiddiqui@gmail.com
1
Department of Chemistry, University of Allahabad,
Allahabad, India
2
Laboratory of Green Synthesis, Department of Chemistry,
University of Allahabad, Allahabad 211002, India
Vol.:(0123456789)
1 3

N. Yadav et al.
Fig. 1 Some biologically active heterocycles containing 1,4-benzothiazine derivatives
moiety via C–S bond formation under metal-free condi-
tions is highly desirable.
2 Experimental Section
In recent years development of sustainable strate-
gies that minimize pollution in chemical synthesis has
received increasing attention from the synthetic com-
munity [17–19]. In this context, visible light mediated
catalysis using visible light as a clean, inexpensive and
renewable energy source has been established as a pow-
erful and mild technique to achieve this goal [20–23]. A
variety of elegant visible-light-driven reactions to con-
struct C–C and C–X (heteroatom) bonds have been well
established [24–27]. Here we are intrigue by the feasi-
bility of a merge of visible-light-induced reaction with
free radical chemistry to develop a conceptually novel
approach for the synthesis of 1,4-benzothiazine deriva-
tives. Recently free radical reactions gained much interest
because of their special activities and strong tendency to
form chemical bond [28–30]. The facile synthesis of sul-
phur radicals from readily available thiols and the appli-
cation of isocyanide as highly efficient radical acceptors
[31] that facilitate the addition of various radicals to the
isocyanide carbon atom [32] substantiate our hypothesis
and furnish the desired 1,4-benzothiazine moiety effi-
ciently through the formation of new C–S bond under
photochemical activation. Mild conditions, short reaction
times and high yields, are some other advantages of our
designed protocol (Scheme 1).
2.1 Materials and Methods
Reagent grade chemicals were purchased from Sigma-
Aldrich and were used as received. Solvents were purified
by the usual methods and stored over molecular sieves. All
reactions were performed using oven-dried glassware under
a nitrogen atmosphere. Organic solutions were concentrated
using a Buchi rotatory evaporator. All reactions were moni-
tored by TLC on Merck 60F254, with detection by UV light.
Melting points were determined by open glass capillary
method and are uncorrected. FTIR spectra were recorded
on a Perkin-Elmer RX-1 spectrophotometer using either
KBr pellets or neat. 1H and 13C NMR spectra were recorded
on a Bruker Avance 400 and 100 MHz NMR spectrometer
in CDCl3 or DMSO using TMS as internal reference with
chemical shift value being reported in ppm. All coupling
constants (J) are reported in Hertz (Hz). MS (EI) spectra
were recorded on double focusing mass spectrometer.
2.2 General Procedure for Synthesis
of 3‑Aryl‑4H‑benzo[1,4]thiazin‑2‑amines
(4a–4g)
A mixture of the aromatic aldehyde 1 (1 mmol), o-ami-
nothiophenol (1 mmol), cyclohexylisocyanide (1 mmol), in
EtOH:H2O (5 mL) was stirred for desired time under visible
light progress of the reaction was monitored by TLC. The
product was precipitated by addition of 10 mL of H2O. The
Scheme 1 Synthesis of
cyclohexyl-3-aryl-4H-
benzo[1,4]thiazin-2-amines
1 3

Visible-Light-Mediated Synthesis of 4H-benzo[1,4]thiazin-2-amines and…
precipitate was filtered off and washed with H2O. The resi-
due was crystallized from EtOH to give the pure product.
[M+]. Anal. Calcd (%) for C21H24N2S: C, C, 74.49; H, 6.88;
N, 8.69. Found: C, 79.82; H, 7.22; N, 8.23.
2.2.1 N-cyclohexyl-3-(4-N-cyclohexyl)-3-(4-hydroxyphenyl)
-4H-benzo[1,4]thiazin-2-amine (4a)
2.2.5 N-cyclohexyl-3-(4-chlorophenyl)-4H-benzo[1,4]
thiazin-2-amine (4e)
1
Mp 184 °C. IR (KBr): 3165, 3145 (νmax/cm−1). H NMR
1
Mp 204 °C. IR (KBr): 3180, 3166 (νmax/cm−1). H NMR
(400 MHz, CDCl3): δ = 1.16–2.25 (m, 10H), 3.38 (m,
1H), 4.24 (s, 1H, NH), 4.60 (s, 1H, NH), 4.95 (s, 1H, OH),
7.36–8.07 (m, 8H, arom.) ppm. 13C NMR (100 MHz,
CDCl3): δ = 23.45, 24.86 (2CH2), 26.74 (2CH2), 52.17,
121.15 (2CH), 123.33, 124.30 (2CH), 125.27, 130.94,
131.48, 133.53, 137.18, 139.15, 143.03, 148.84,
149.21 ppm. GCMS: m/z=338 [M+]. Anal. Calcd (%) for
C20H22N2SO: C, 70.97; H, 6.56; N, 8.28. Found: C, 70.83;
H, 6.37; N, 8.13.
(400 MHz, CDCl3): δ=1.20–2.21 (m, 10H), 3.44 (m, 1H),
4.37 (s, 1H, NH), 4.64 (s, 1H, NH), 7.46–8.28 (m, 8H,
arom.) ppm. 13C NMR (100 MHz, CDCl3): δ=22.37, 26.49
(2CH2), 33.63 (2CH2), 49.20, 121.86 (2CH), 123.57, 124.15
(2CH), 127.17, 129.69, 130.35, 131.53, 138.49, 140.28,
142.39, 147.85, 149.97 ppm. GCMS: m/z = 356 [M+].
Anal. Calcd (%) for C20H21N2SCl: C, 67.30; H, 5.93; N,
7.85. Found: C, 67.13; H, 5.65; N, 7.93.
2.2.6 N-cyclohexyl-6-methyl-3-phenyl-4H-benzo[1,4]
2.2.2 N-cyclohexyl-3-(4-nitrophenyl)-4H-benzo[1,4]
thiazin-2-amine (4f)
thiazin-2-amine (4b)
1
Mp 241 °C. IR (KBr): 3160, 3153 (νmax/cm−1). H NMR
1
Mp 204 °C. IR (KBr): 3180, 3166 (νmax/cm−1). H NMR
(400 MHz, CDCl3) δ = 1.12–2.24 (m, 10H), 3.05 (s, 3H),
3.60 (m, 1H), 4.68 (s, 1H, NH), 4.96 (s, 1H, NH), 7.26–7.91
(m, 8H, arom.) ppm. 13C NMR (100 MHz, CDCl3):
δ=24.13, 24.45 (2CH2), 28.86 (2CH2), 30.96, 47.96, 121.97
(2CH), 124.46, 124.78, 125.35, 126.88 (2CH), 127.17,
130.85, 131.45, 136.57, 137.92, 138.45, 140.96 ppm.
GC–MS: m/z=336 [M+]. Anal. Calcd (%) for C21H24N2S:
C, 74.96; H, 7.19; N, 8.32. Found: C, 74.87; H, 7.07; N,
8.23.
(400 MHz, CDCl3): δ=1.20–2.21 (m, 10H), 3.44 (m, 1H),
4.37 (s, 1H, NH), 4.64 (s, 1H, NH), 7.46–8.28 (m, 8H,
arom.) ppm. 13C NMR (100 MHz, CDCl3): δ=22.37, 26.49
(2CH2), 33.63 (2CH2), 49.20, 121.86 (2CH), 123.57, 124.15
(2CH), 127.17, 129.69, 130.35, 131.53, 138.49, 140.28,
142.39, 147.85, 149.97 (CCl) ppm. GCMS: m/z=356 [M+].
Anal. Calcd (%) for C20H21N2SCl: C, 67.30; H, 5.93; N,
7.85. Found: C, 67.13; H, 5.65; N, 7.93.
2.2.3 N-cyclohexyl-3-phenyl-4H-benzo[1,4]thiazin-2-amine
2.2.7 N-tert-butyl-3-phenyl-4H-benzo[1,4]thiazin-2-amine
(4c)
(4g)
1
Mp 190 °C. IR (KBr): 3169, 3155 (νmax/cm−1). H NMR
1
Mp 232 °C. IR (KBr): 3162, 3147 (νmax/cm−1). H NMR
(400 MHz, CDCl3): δ=1.12–2.14 (m, 10H), 3.54 (m, 1H),
4.34 (s, 1H, NH), 4.67 (s, 1H, NH), 7.40–7.92 (m, 9H,
arom.) ppm. 13C NMR (100 MHz, CDCl3): δ=23.23, 24.69
(2CH2), 28.84 (2CH2), 47.74, 121.13 (2CH), 123.35, 123.96,
124.76, 126.93 (2CH), 127.74, 130.09, 131.14, 136.13,
137.95, 138.83, 140.34 ppm. GC–MS: m/z = 322 [M+].
Anal. Calcd (%) for C20H22N2S: C, 74.47; H, 6.86; N, 8.67.
Found: C, 73.96; H, 6.37; N, 8.53.
(400 MHz, CDCl3): δ = 1.34 (s, 9H), 4.16 (s, 1H, NH),
4.66 (s, 1H, NH), 7.26–7.97 (m, 9H, arom.) ppm. 13C NMR
(100 MHz, CDCl3): δ=26.38 (3 CH3), 40.47, 122.57 (2CH),
124.66, 124.89, 125.44, 126.88 (2CH), 128.75, 131.76,
132.87, 136.86, 137.64, 138.95, 141.56 ppm. GC–MS:
m/z=296 [M+]. Anal. Calcd (%) for C18H20N2S: C, 72.93;
H, 6.80; N, 9.45. Found: C, 72.86; H, 6.64; N, 9.36.
2.2.4 N-cyclohexyl-3-(4-methylphenyl)-4H-benzo[1,4]
2.2.8 N-cyclohexyl-3-ethyl-3-methyl-3,
thiazin-2-amine (4d)
4-dihydroquinoxalin-2-amine (7a)
Mp 209 °C. IR (KBr):3165, 3153 cm−1. 1H NMR (400 MHz,
CDCl3): δ = 1.14–2.26 (m, 10H), 2.46 (s, 3H), 3.65 (m,
1H), 4.41 (s, 1H, NH), 4.74 (s, 1H, NH), 7.27–8.04 (m, 8H,
arom.) ppm. 13C NMR (100 MHz, CDCl3): δ=23.15, 24.16
(2CH2), 27.19 (2CH2), 40.82, 53.513, 124.65 (2CH), 122.56,
125.42 (2CH), 127.15, 128.72, 129.27, 137.15, 138.54,
140.67, 141.07, 143.93, 149.91 ppm. GC–MS: m/z = 336
White solid; mp 220 °C; IR (KBr): 3297, 2930, 2866, 1646,
1
1617, 1512, 1450, 1217, 1172, 752, 683 (νmax/cm−1); H
NMR (400 MHz, DMSOd6): δ = 0.86 (t, J = 3.0 Hz, 3H,
CH2CH3), 1.37 (q, J = 2.8 Hz, 2H, –CH2–), 1.47 (s, 3H,
–CH3), 1.13–2.36 (m, 10H, 2–5CH2 of cyclohexyl), 3.97 (br
s, 1H, –CH–NH), 6.33–6.43 (br s, 1H, –NH), 6.72–6.76 (br
s, 1H, –NH), 6.76–7.67 (m, 4H, Ar–H) ppm; Anal. Calcd for
1 3

N. Yadav et al.
C17H25N3: C, 75.25; H, 9.26; N, 15.46%. Found: C, 75.22;
H, 9.26; N, 15.47%.
2.2.13 6-Chloro-N-cyclohexyl-3-methyl-3-phenyl-3,
4-dihydroquinoxalin-2-amine (7f)
Pale pink solid; mp 249 °C; IR (KBr): 3255, 2936, 2861,
1648, 1617, 1503, 1458, 1216, 1184, 814, 684 (νmax/cm−1);
1H NMR (400 MHz, DMSOd6): δ=1.06–2.26 (m, 10H, 2
–5CH2 of cyclohexyl), 1.42 (s, 3H, –CH3), 3.94–4.17 (br s,
1H, –CH–NH), 6.72–6.86 (br s, 1H, –NH), 6.90–7.09 (br
s, 1H, –NH), 7.08–7.88 (m, 8H, Ar–H) ppm; Anal. Calcd
forC21H24ClN3: C, 71.27; H, 6.84; N, 11.87%. Found: C,
71.25; H, 6.84; N, 11.82%.
2.2.9 N-cyclohexyl-3-methyl-3-phenyl-3,
4-dihydroquinoxalin-2-amine (7b)
Pale yellow solid; mp 308 °C; IR (KBr): 3302, 3256, 2934,
2865, 1647, 1623, 1516, 1460, 1215, 1177, 754, 685 (νmax
/
cm−1); 1H NMR (400 MHz, DMSO-d6): δ=1.04–2.35 (m,
10H, 2−5CH2 of cyclohexyl), 1.87 (s, 3H, –CH3), 4.07 (br
s, 1H, –CH–NH), 6.62–6.73 (br s, 1H, –NH), 6.97–6.99 (br
s, 1H, –NH), 7.07–7.65 (m, 9H, Ar–H) ppm; Anal. Calcd for
C21H25N3: C, 78.96; H, 7.89; N, 13.15%. Found: C, 78.95;
H, 7.84; N, 13.12%.
2.2.14 3-(2-Aminophenyl)-6-chloro-N-cyclohexyl-3
-methyl-3,4-dihydroquinoxalin-2-amine (7g)
Pale pink solid; mp 259 °C; IR (KBr): 3275, 2927, 2855, 1648,
1627, 1517, 1456, 1405, 1203, 1182, 815, 684 (νmax/cm−1);
1H NMR (400 MHz, DMSO-d6): δ=1.02–2.26 (m, 10H, 2
–5CH2 of cyclohexyl), 1.42 (s, 3H, –CH3), 3.85–3.92 (br s,
1H, –CH–NH), 6.67–6.72 (br s, 1H, –NH), 6.77–6.76 (br s,
1H, – NH), 6.76–7.52 (m, 7H, Ar–H) ppm; Anal. Calcd for
C21H25ClN4: C, 68.37; H, 6.83; N, 15.19%. Found: C, 68.35;
H, 6.82; N, 15.10%.
2.2.10 3-(4-Bromophenyl)-N-cyclohexyl-3-methyl-3,
4-dihydroquinoxalin-2-amine (7c)
White solid; mp 263 °C; IR (KBr): 3257, 2935, 2868,
1646, 1622, 1511, 1453, 1204, 1194, 751, 682 (νmax/cm−1);
1H NMR (400 MHz, DMSO-d6): δ = 1.02–2.27 (m, 10H,
2–5CH2– of cyclohexyl), 1.37 (s, 3H, –CH3), 3.95 (br s,
1H, –CH–NH), 6.55 (br s, 1H, –NH), 6.75 (br s, 1H, –NH),
6.77–7.53 (m, 8H, Ar–H) ppm; Anal. Calcd for C21H24BrN3:
C, 63.32; H, 6.07; N, 10.55%. Found: C, 63.30; H, 6.04; N,
10.54%.
2.2.15 3-(4-Bromophenyl)-6-chloro-N-cyclohexyl-3
-methyl-3,4-dihydroquinoxalin-2-amine (7h)
Violet solid; mp 221 °C; IR (KBr): 3272, 2936, 2868, 1642,
1624, 1507, 1454, 1209, 1187, 821, 682 (νmax/cm−1); 1H NMR
(400 MHz, DMSOd6): δ=1.04–2.29 (m, 10H, 2 –5CH2 of
cyclohexyl), 1.35 (s, 3H, –CH3), 4.03 (br s, 1H, –CH–NH),
6.66–6.72 (br s, 1H, –NH), 6.77–6.83 (br s, 1H, –NH),
6.87–7.55 (m, 7H, Ar–H) ppm; Anal. Calcd for C21H23BrClN3:
C, 58.28; H, 5.36; N, 9.71%. Found: C, 58.20; H, 5.26; N,
9.63%.
2.2.11 N-cyclohexyl-3-methyl-3-phenyl-3,
4-dihydroquinoxalin-2-amine (7d)
White solid; mp 205 °C; IR (KBr): 3247, 2935, 2863, 1648,
1626, 1506, 1456, 1399, 1208, 1182, 756, 684 (νmax/cm−1);
1H NMR (400 MHz, DMSO-d6): δ = 1.07–2.33 (m, 10H,
2–5CH2– of cyclohexyl) 1.35 (s, 3H, –CH3), 1.36–1.52
(s, 3H, –CH3 of 4-methylacetophenone), 3.87 (br s, 1H,
–CH–NH), 6.31–6.43 (br s, 1H, –NH), 6.67–6.75 (br s,
1H, –NH), 6.73–7.57 (m, 8H, Ar–H) ppm; Anal. Calcd for
C22H27N3: C, 79.24; H, 8.16; N, 12.60%. Found: C, 79.24;
H, 8.16; N, 12.54%.
2.2.16 6-Chloro-N-cyclohexyl- 3-methyl-3-(p-tolyl)-3,
4-dihydroquinoxalin-2-amine (7i)
Brown solid; mp 236 °C; IR (KBr): 3276, 2922, 2857, 1645,
1616, 1517, 1455, 1206, 1184, 814, 683 (νmax/cm−1); 1H NMR
(400 MHz, DMSO-d6): δ=0.96–2.22 (m, 10H, 2 –5CH2 of
cyclohexyl), 1.35 (s, 3H, –CH3), 2.28 (s, 3H, –CH3 of 4-methyl
acetophenone), 4.02 (br s, 1H, –CH–NH), 6.56–6.72 (br s, 1H,
–NH), 6.76–6.75 (br s, 1H, –NH), 6.75–7.47 (m, 7H, Ar) ppm;
Anal. Calcd for C22H26ClN3: C, 71.82; H, 7.12; N, 11.42%.
Found: C, 71.76; H, 7.10; N, 11.34%.
2.2.12 6-Chloro-N-cyclohexyl-3-ethyl-3-methyl-3,
4-dihydroquinoxalin-2-amine (7e)
Pure light gray ash color solid; mp 193 °C; IR (KBr): 3265,
2937, 2862, 1646, 1625, 1504, 1457, 1202, 1193, 817, 684
1
(νmax/cm−1); H NMR (400 MHz, DMSO-d6): δ = 0.85 (t,
J=3.0 Hz, 3H, –CH2CH3), 1.24 (q, J=2.8 Hz, 2H, –CH2–),
1.52 (s, 3H, –CH3), 1.32–2.35 (m, 10H, 2 –5CH2 of
cyclohexyl), 3.95–4.06 (br s, 1H, –CH–NH), 6.47–6.58 (br
s, 1H, – NH), 6.70–6.82 (br s, 1H, –NH), 6.87–7.63 (m, 3H,
Ar–H) ppm; Anal. Calcd for C17H24ClN3: C, 66.76; H, 7.91;
N, 13.74%. Found: C, 66.75; H, 7.84, N, 13.72%.
1 3

Visible-Light-Mediated Synthesis of 4H-benzo[1,4]thiazin-2-amines and…
Subsequently, different ratios of ethanol:water were
evaluated and the studies showed that the use of 1:1 mix-
ture ethanol in water proved to be the optimum solvent
(Table 1, Entry 6) and inferior yields were obtained when we
increased the amount of water (Table 1, Entry 7). However,
conversion was almost negligible when performed under
solvent-free condition (Table 2, Entry 8). Inspired by the
common photoredox catalysts, that usually play important
roles in photoredox catalysis, many typical photocatalysts,
such as eosin Y, rose bengal and Ru(bpy)3Cl2, were also
investigated to improve the reaction efficiency. However, no
consequential distinction was detected in yield of the prod-
uct or in the reaction time. (Table 1, Entries 9–11).
3 Results and Discussion
Initially benzaldehyde (1 mmol), cyclohexylisocyanide
(1 mmol), and o-aminothiophenol (1 mmol) were used
as a model substrates for obtaining 1,4-benzothiazine at
room temperature. Reaction was irradiated with 22 W
CFL in a variety of organic solvents that were commonly
employed for example THF, DCM, methanol and ethanol.
Progress of reaction was monitored by TLC. We detected
non-expenditure of the reactants in case of THF and the
yield of desired product was not good (Table 1, Entry 1).
Reaction in DCM was also not proceeded effectively and
gave only 59% yield of the product (Table 1, Entry 2).
Further, to gain an enhancement in the product yield, we
increased the polarity of solvents and reaction was carried
out in methanol and ethanol subsequently (Table 1, Entries
3, 4). Pleasingly, the yield of product increased up to 75%
when reaction was carried out in ethanol. It is fascinating
to reveal that the polar solvents furnished better yield in
contrast to the non-polar solvent. With the aim, to reduce
the environmental impact and to minimize the amount of
organic solvent used in our process, water was added in
ethanol. Surprisingly, an encouraging change in the yield
was noticed and reaction time was reduced after the addi-
tion of water as a co-solvent in ethanol (Table 1, Entry 5),
may be due to the fact that polar reaction media facilitate
the cyclisation reaction [33]. In addition, mixing of water
has not only beneficial in context of yield and sustainabil-
ity but also facilitated product separation from the reaction
mixture because being highly polar it is immiscible with
organic compounds. In this way we reduced the tedious
workup, waste, labour and cost.
Next, we turned to testing the effect of intensity of visible
light on this reaction (Table 2). For this purpose a series
of experiments were carried out by using CFL of differ-
ent watts. Results revealed that highest yield was obtained
within minimum reaction times when 22 W CFL was used
(Table 2, Entry 2).CFL of higher watt (24 W) did not have
any appreciable effect on the yield. However, yield of the
product was significantly lower when we used CFL of lower
intensity (Table 2, Entry 1). The daylight and LED was not
much more effective for this reaction (Table 2, Entry 4 and
5).
Once perfect requirements for accomplishing this reaction
had been determined, the opportunity and obstruction of the
developed synthetic procedure were searched for the syn-
thesis of a series of 4H-benzo[1,4]thiazin-2-amines deriva-
tives by reacting a variety of aromatic aldehyde with alkyl
isocyanide. It was observed that all the reaction proceeded
Table 2 Optimization of source and visible light intensity for the syn-
thesis of compound 4a
Entry
Source
Time (h)
Yield (%)a
Table 1 Optimization of reaction conditions for the synthesis of com-
pound 4a
1
2
3
4
5
6
CFL (18 W)b
CFL (22 W)c
CFL (24 W)d
LED (4.45 W)e
Daylight
10
78
91
91
80
60
Traces
Entry Solvent
Photocatalyst Time (h) Yield (%)a
4.5
4.5
8
>12
24
1
2
3
4
5
6
7
8
THF
DCM
MeOH
EtOH
–
–
–
–
–
–
–
–
12
12
10
6
4.5
4.5
8
12
7
5
37
59
65
75
86
91
80
15
85
80
89
Dark
EtOH:water (3:2)
EtOH:water (1:1)
EtOH:water (2:3)
–
EtOH:water (1:1) Eosin Y
EtOH:water (1:1) Rose bengal
EtOH:water (1:1) Ru(bpy)3Cl2
Reaction conditions: benzaldehyde (1 mmol), cyclohexyl-isocyanide
(1 mmol), and o-aminothiophenol (1 mmol), in 8 mL EtOH:water
(1:1) solvent at room temperature
aYields of isolated pure product
b18 W CFL (compact fluorescent lamp, Philips, 6500 K, 1010 lm,
85 mA) was used for irradiation
9
10
11
c22 W CFL (compact fluorescent lamp, Philips, 6500 K, 1250 lm,
95 mA) was used for irradiation
4.5
d24 W CFL (compact fluorescent lamp, Philips, 6500 K, 1450 lm,
110 mA) was used for irradiation
Reaction conditions: benzaldehyde (1 mmol), cyclohexylisocyanide
(1 mmol), and o-aminothiophenol (1 mmol), in 8 mL EtOH:water
(1:1) solvent under 22 W CFL irradiation at room temperature
eBlue LEDs 4.45 W, λ=447.5 nm were used for irradiation at 2 cm
distance from the flask bottom side
aYields of isolated pure product
1 3

N. Yadav et al.
Table 3 Scope of substrate for the synthesis of compound 4
Entry
R1
R2
Ar
Product
Yield (%)a
87
1
H
c-Hexyl
4-HOC6H4
4a
2
3
H
H
c-Hexyl
c-Hexyl
4-O2NC6H4
90
88
4b
Ph
4c
4
5
H
H
c-Hexyl
c-Hexyl
4-MeC6H4
4-ClC6H4
88
90
4d
4e
6
Me
c-Hexyl
Ph
89
4f
7
H
t-Butyl
Ph
89
4g
1 3

Visible-Light-Mediated Synthesis of 4H-benzo[1,4]thiazin-2-amines and…
Table 3 (continued)
Reaction conditions: aromatic aldehyde (1 mmol), isocyanide (1 mmol), and o-aminothiophenol (1 mmol), in 8 mL EtOH:water (1:1) solvent
under, 22 W CFL irradiation at room temperature
aYields of isolated pure product
efficiently and furnished the desired products in good to
excellent yields (Table 3).
resulted in the formation of desired product. To affirm the
generation of sulphur and carbon free radical during the
reaction, radical-trapping experiments were performed [35].
As we observed when reaction was conducted in the pres-
ence of the 1.0 equiv. of TEMPO, radical inhibitor, yield of
the product was reduced. Where as on further increasing the
amount of TEMPO the reaction was fully suppressed. This
observation indicated that a radical addition pathway might
be involved in this conversion.
Further, in order to reveal the common relevancy of our
proposed protocol, we explored this visible light induced
reaction with ketones and diamines and in place of aro-
matic aldehyde and aminothiophenol. Surprisingly, under
the previously optimized condition, a variety of 3,4-dihyd-
roquinoxalin-2-amine derivatives (Table 4) were obtained in
good to excellent yield. Notably, an electron donating aryl
group slowed down the reaction and contraction in yield
while the presence of an electron withdrawing aryl group
fastened the reaction and induced the yield of the desired
product. These successful results clearly demonstrate that
the proposed protocol is extendable to a wide range of sub-
strates and expected to be highly significant in the field of
drug discovery and diversity oriented synthesis.
4 Conclusion
In conclusion, we have described a highly efficient, sim-
ple, visible light mediated, green synthetic one-pot, three
component procedure for the preparation of 3-aryl-4H-
benzo[1,4]thiazin-2-amines. This is the first synthesis of
benzothiazine using renewable source of energy (visible
light) under metal free condition. This custom allocates
a mild and appropriate reaction conditions and provides
a green and facile procedure for the development of the
desired products. Elimination of transition metal cata-
lyst, operational simplicity, eco-friendly conditions, short
reaction times, easy workup procedure, high atom econ-
omy and excellent yields are the other significant features
of our described protocol.
On the basis of the above experimental observations
and literature precedents [34] we proposed the plausible
mechanism for the synthesis of 3-aryl-4H-benzo[1,4]thia-
zin-2-amines. As shown in scheme 2 reaction was inaugu-
rated by the origination of intermediate (I) formed through
the reaction of aromatic o-aminothiophenol 1 and aldehyde
2 which subsequently attacked by isocyanide 3 resulting
intermediate (II). Then under visible light stimulation sul-
phur radical was furnished which attacked on the carbon
radical generating intermediate (IV) followed by 1,3-H shift
1 3

N. Yadav et al.
Table 4 Scope of substrate for the synthesis of compound 7
Entry
1.
Diamine
Ketone
Isocyanide
Product
Time
(h)
Yield
(%)a
2.5
96
2.
4
93
3.
4.
3
3
91
7c
97
95
7d
5.
6.
2
4
7e
7f
90
7.
2
89
7g
8.
9.
3
4
83
92
7h
7i
1 3

Visible-Light-Mediated Synthesis of 4H-benzo[1,4]thiazin-2-amines and…
Table 4 (continued)
Reaction conditions: ketones (1 mmol), isocyanide (1 mmol), and diamines (1 mmol) in 8 mL EtOH:water (1:1) solvent under, 22 W CFL irra-
diation at room temperature
aYields of isolated pure product
Scheme 2 A plausible mecha-
nism for C–S and C–N bond
formation and synthesis of
3-aryl-4H-benzo[1,4]thiazin-
2-amine
Tautomerisation
Acknowledgements The authors gratefully acknowledge SAIF, Punjab
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