Photochemical synthesis of triazolo[3,4-b]-1,3(4H)-benzothiazines: A detailed mechanistic study on photocyclization/photodesulfurisation of triazole-3-thiones

Article abstract of DOI:10.1016/j.tet.2003.11.053

Irradiation of 4-(2-halobenzyl)-5-substituted-1,2,4-triazole-3-thiones under base mediated (CH₃CN/2 M NaOH) condition afforded triazolo[3,4-b]-1,3(4H)-benzothiazines and desulfurized triazoles. Benzophenone sensitized photolysis of triazole-3-thiones gave desulfurized triazoles exclusively. The mechanism of the photocyclization/photodesulfurization and the involvement of singlet and triplet energy levels are discussed.

Full text of DOI:10.1016/j.tet.2003.11.053

Tetrahedron 60 (2004) 851–860
Photochemical synthesis of triazolo[3,4-b]-1,3(4H)-
benzothiazines: a detailed mechanistic study on
photocyclization/photodesulfurisation of triazole-3-thiones
*
A. Senthilvelan, D. Thirumalai and V. T. Ramakrishnan
Department of Organic Chemistry, School of Chemical Sciences, University of Madras, Guindy Campus, Chennai 600 025, India
Received 4 September 2003; revised 30 October 2003; accepted 20 November 2003
Abstract—Irradiation of 4-(2-halobenzyl)-5-substituted-1,2,4-triazole-3-thiones under base mediated (CH3CN/2 M NaOH) condition
afforded triazolo[3,4-b]-1,3(4H)-benzothiazines and desulfurized triazoles. Benzophenone sensitized photolysis of triazole-3-thiones gave
desulfurized triazoles exclusively. The mechanism of the photocyclization/photodesulfurization and the involvement of singlet and triplet
energy levels are discussed.
q 2003 Elsevier Ltd. All rights reserved.
1. Introduction
thiazines and desulfurization of 1,2,4-triazole-3-thiones.7 In
this paper, we discuss the synthesis and mechanistic aspects
on the formation of triazolo benzothiazines and desulfuriza-
tion of triazole-3-thiones on irradiation under basic and
triplet sensitized conditions.
The photochemistry of thiocarbonyl compounds has
received much attention from both synthetic and mechan-
istic points of views. Earlier workers from our laboratories
reported1 the synthesis of condensed benzothiazoles from
thioamides, such as the synthesis of s-triazolo[3,4-b]-
benzothiazoles (Scheme 1) from 4-(o-halophenyl)-5-sub-
stituted 1,2,4-triazole-3-thiones by photolysis. Recently, we
reported the synthesis of isoquinoline-fused benzoxazole
and benzoxazine systems, under base mediated photolytic
conditions.2
2. Results and discussion
Refluxing a mixture of o-halobenzyl isothiocyanate
(1 equiv.) and the substituted acid hydrazide (1 equiv.) in
ethanol8 afforded the corresponding thiosemicarbazides
which were directly converted into the respective 4-(o-
halobenzyl)-5-substituted-1,2,4-triazole-3-thiones 1a–g in
good yield (Scheme 2) using 10% K2CO3 (Table 1).
The structures of triazole-3-thiones 1a–g were confirmed
by spectral and analytical data. IR spectra of thiones 1a–g
were comparable with those reported in the literature.9,10
The presence of a strong band in the region of 1300 cm21
corresponds to the thione (–CvS) form and a weak band
around 2600 cm21 indicates the thiol (–SH) form. In the 1H
NMR of the triazole-3-thiones, a singlet around d 13 showed
Scheme 1.
In continuation of our interest in the synthesis of
biologically active nitrogen and sulfur containing hetero-
cycles, and the importance of triazole fused benzothiazine
ring systems,3–6 we focused our work on the synthesis of
condensed benzothiazines. In a preliminary communication,
we reported the synthesis of triazolo[3,4-b]-1,3(4H) benzo-
Table 1. Synthesis of substituted 1,2,4-triazole-3-thiones 1a–g
Compound
R1
X
1a
1b
1c
1d
1e
1f
Phenyl
p-Tolyl
p-Anisyl
o-Tolyl
Benzyl
o-Chlorophenyl
o-Chlorophenyl
Cl
Cl
Cl
Br
Cl
Cl
Br
Keywords: Cyclization; Benzothiazines; Desulfurization; Triazoles.
*
Corresponding author. Tel.: þ91-44-2235-1269x213; fax: þ91-44-2235-
1g
2494; e-mail address: vtrk28@yahoo.com
0040–4020/$ - see front matter q 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2003.11.053

852
A. Senthilvelan et al. / Tetrahedron 60 (2004) 851–860
Scheme 2.
the presence of –SH proton. 13C NMR also showed the
presence of thiocarbonyl carbon around d 169. In the 13C
NMR, the thiocarbonyl carbon appears upfield compared to
the carbonyl carbon signal.11 The signal at d 160 for the
above compounds could be represented as for the thiol form.
The photosubstitution reaction described here would
involve the intramolecular displacement of the halogen
atom present in the N-benzyl moiety of the triazole-3-
thiones 1a–e by the thiocarbonyl sulphur of the thioamide.
The photodesulfurization would take place in the thiol
(–SH) form of the triazole-3-thiones.
The 1H NMR spectra of 1a exhibited a singlet at d 5.37 for
the –CH2 protons, a multiplet between d 6.96–7.46 for
aromatic protons and a singlet at d 13.88 for the –SH
proton. The 13C NMR spectrum of 1a showed a peak at d
45.7 for –CH2 carbon, which was confirmed by the DEPT-
135 spectrum, which showed –CH2 carbon as an inverted
peak. The X-ray crystallography data confirmed the
structure of 1b.12
In the presence of base such as NaOH, the UV–Vis
absorption behaviour of thione 1a (lmax¼262 nm) in
CH3CN changed to lmax¼300 nm. The absorption at
300 nm in the UV spectra is believed to be the formation
of anionic form of the triazole-3-thione, due to deprotona-
tion by base. Thus, the anionic species is formed in solution,
which induces the photosubstitution reaction. When the
irradiation of 1a was carried out in acetonitrile containing
weak bases such as aqueous K2CO3 (0.5 M) or NaOH
(0.5 M) (entries 4, 5 in Table 2), the product 2a was formed
in lower yield compared to using 2 M NaOH conditions
(entry 6). A Similar trend was observed in the case of 1b
(entries 7, 8) also. Probably an anionic thiol of the thioamide
bond was not efficiently populated in this medium for the
substitution reaction.
2.1. Irradiation studies
The irradiation experiments were carried out at 254 nm in
an Applied Photophysics multilamp reactor (MLR). The
various conditions are tabulated in Table 2. An acetonitrile
solution (150 mL) of 4-(2-chlorobenzyl)-5-phenyl-1,2,4-
triazole-3-thione 1a (0.3 g, 0.9 mmol) containing 30 mL
of aqueous 2 M NaOH (entry 6 in Table 2) was flushed with
nitrogen for 1 h and irradiated at 254 nm for 18 h; workup and
chromatographic purification furnished the photosubstituted
3-phenyl-1,2,4-triazolo [3,4-b]-1,3(4H)-benzothiazine 2a
(41%) and photodesulfurized 4-(2-chlorobenzyl)-5-phenyl-
1,2,4-triazole 3a (10%). Similarly, irradiation of triazole-3-
thiones 1b–e (entries 8, 9, 11 and 12 in Table 2) in
CH3CN containing 2 M NaOH in MLR for 11–21 h,
furnished the corresponding photosubstituted triazoloben-
zothiazines 2b–e and photodesulfurized triazoles 3b,c. In
the case of 1d,e, no desulfurized product was observed
(Scheme 3).
The irradiation of 1a in protic solvent (methanol) containing
0.5 M K2CO3 or 0.5 M NaOH (entries 2,3) was carried out;
the formation of desulfurized product 3a increased by
more than three times compared to the substituted product
2a. This is due to the proton donor behavior of methanol,
which probably inhibits the substitution by blocking the
formation of anionic sulphur of 1a by its protonation, which
invariably increases the population of the thiol (–SH) form.
In order to study the reaction pathway for the photosubstitu-
tion and photodesulfurization of triazole-3-thiones, the
photolysis of thione 1a was carried out under nitrogen as
Scheme 3.

A. Senthilvelan et al. / Tetrahedron 60 (2004) 851–860
Table 2. Irradiation of triazole-3-thiones 1a-g under various reaction condition
853
Entry
Compound
Reaction medium
R1
Reaction time (h)
X
2 Yield (%)
3 Yield (%)
1
2
3
4
5
6
7
8
1a
1a
1a
1a
1a
1a
1b
1b
1c
1d
1d
1e
1f
CH3OH/Ph2CO
Ph
Ph
Ph
Ph
Ph
Ph
p-Tolyl
p-Tolyl
p-Anisyl
o-Tolyl
62
45
30
20
20
18
22
17
20
48
11
21
32
13
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Br
Br
Cl
Cl
Br
-
67
50
48
15
16
10
11
8
15
71
-
-
47
48
CH3OH/0.5 M K2CO3
CH3OH/0.5 M NaOH
CH3CN/0.5 M K2CO3
CH3CN/0.5 M NaOH
CH3CN/2 M NaOH
CH3CN/0.5 M NaOH
CH3CN/2 M NaOH
CH3CN/2 M NaOH
CH3OH/Ph2CO
CH3CN/2 M NaOH
CH3CN/2 M NaOH
CH3CN/2 M NaOH
CH3CN/2 M NaOH
11
15
30
32
41
38
47
38
-
9
10
11
12
13
14
o-Tolyl
Benzyl
o-Chlorophenyl
o-Chlorophenyl
50
45
-
1g
-
well as oxygen atmosphere. Hence, an acetonitrile solution
(50 mL) of 1a (0.1 g) containing aqueous NaOH (0.5 M,
10 mL), was irradiated in a MLR (254 nm) for 20 h under
nitrogen (or oxygen) atmosphere. The photoproducts of the
reaction mixture were analysed by HPLC. Under a nitrogen
atmosphere, the photosubstitution reaction is faster than the
photodesulfurization (entry 1 in Table 3). Whereas, in
oxygen atmosphere, which is a triplet quencher, the
substitution reaction was not affected, but the desulfuriza-
tion was reduced considerably (entry 2 in Table 3).
Thus, one possible explanation for the formation of the
photosubstitution product is that an anionic nucleophile of
thiocarbonyl sulphur of triazole-3-thione in basic medium
intramolecularly displaces the halogen of the haloarene in
the singlet excited state (SN2Arp).14 Another possibility is
that an anionic radical species photoinduced from anionic
thiocarbonyl sulphur of the thioamide bond in basic medium
intramolecularly substitutes the halogen of the haloarene
(SN(ET)Arp)14 (Scheme 4).
An intramolecular electron transfer mechanism has been
proposed for the formation of 2-(pyridinyl)-benzoxazoles.15
Earlier, we proposed intramolecular electron-transfer mech-
anism for the formation of benzothiazoles from the
photoreaction of o-halothioacetamide,1 and we observed
the Clz22 (anion radical) at lmax ,345 nm by laser flash and
steady state experiments.
The irradiation of 1a (0.3 g) in methanol (180 mL)
containing benzophenone (1.2 equiv.) a triplet sensitizer,
was carried out in a MLR (254 nm) for 62 h (entry 1 in
Table 2) to afford exclusively the desulfurized triazole 3a in
67% yield. In this reaction, no substitution product was
formed. A Similar trend was observed in the irradiation of
the bromo analogue 1d (entry 10 in Table 2). Hence, in the
base mediated irradiation reactions of triazole thiones, a
singlet state is involved for substitution reaction and a triplet
state in the photodesulfurization reaction.
The structure of photoproducts 2 and 3 were consistent with
the spectral and analytical data. The IR spectra of 3-(p-
tolyl)-1,2,4-triazolo-(3,4-b)-1,3(4H)-benzothiazine 2b,
.
showed bands at 1593 (CvN), 748 (C–S) cm21 1H
The irradiation of 4-(2-chlorobenzyl)-5-(2-chlorophenyl)-
1,2,4-triazole-3-thione 1f in CH3CN/2 M NaOH conditions
(entry 13 in Table 2) for 32 h furnished exclusively the
desulfurized triazole 3f. In this reaction, no photosubstituted
product was formed. Similarly, the irradiation of 4-(2-
bromobenzyl)-5-(2-chlorophenyl)-1,2,4-triazole-3-thione
1g in CH3CN/2 M NaOH conditions (entry 14 in Table 2)
also afforded the desulfurized product 3g exclusively. This
is due to the presence of the o-chlorine atom as the 5-aryl
substituent of triazole thione, which increases the popu-
lation of the triplet state involved for the desulfurization of
triazole thiones by enhancing inter system crossing effect
(heavy atom effect).13
NMR spectrum of 2b showed singlets at d 2.45 and 5.20
for CH3 and C4–CH2 protons, while the 13C NMR showed
signals at d 21.44 (CH3), 47.61 (CH2). The mass spectra of
2b showed the molecular ion Mþ (m/z 279) as a base peak.
The mass fragment at m/z 161 indicates the fragmentation of
Ph–CN from the Mþ21 peak. The other compounds follow
the same pattern.
1
The H NMR spectra of photodesulfurized triazoles 3a–
d,f,g exhibited a singlet around d 8 for triazole C5–CH
proton and another singlet around d 5.2 for the methylene
protons. The 13C NMR spectra of triazoles 3 showed a peak
around d 144 for C5–CH carbon of the triazole ring. The
mass spectrum of 3b showed molecular ion Mþ peak (m/z
283). The fragmentation of Clz from molecular ion was
observed (m/z 248).
Table 3. Relative rates of the formation of 2a and 3a
Entry Compound
Reaction medium
Atmosphere
Relative
rate
2.2. Triplet sensitized photolysis of substituted 1,2,4-
triazole-3-thiones 1a–d and 4a–g
2a
3a
1
2
1a
1a
CH3CN/0.5 M NaOH
CH3CN/0.5 M NaOH
N2
O2
2.0 1.0
2.0 0.25
The substituted 1,2,4-triazole-3-thiones 4a–g were syn-
thesized (Scheme 5) from the corresponding acid hydrazide
(1 equiv.) and isothiocyanate (1 equiv.) in good yield
(Table 4). The triazolethiones 4a–e16 and 4f1 were reported
HPLC-Column used—Bondapak C18; Solvent—CH3OH/H20 (8:2);
Rate—1 mL/1 min; UVmax—254 nm (detector).

854
A. Senthilvelan et al. / Tetrahedron 60 (2004) 851–860
Scheme 4.
The desulfurization of 1,2,4-triazole-3-thione by (i) using
Raney Ni/EtOH and (ii) using 17% HNO3, to the
corresponding 1,2,4-triazole is known.18,19 Reaction of 4a
(0.5 g, 1.9 mmol) in the presence of Raney Ni for 23 h,
afforded 5a (47%). Likewise, the treatment of 4b
(2.1 mmol) with 17% HNO3 (50 mL) under reflux for 5 h,
afforded the desulfurized triazole 5b in 55% yield,
compared by mp, mixture mp and superimposable IR.
Scheme 5.
earlier. The structure of compound 4g was confirmed by
spectral and analytical data, and XRD.17
Benzophenone sensitized irradiation of 4-(2-chlorophenyl)-
5-phenyl-1,2,4-triazole-3-thione 4f in methanol for 50 h
afforded the desulfurized 3-phenyl-4-(2-chlorophenyl)-
1,2,4-triazole 5f, instead of the respective triazolobenzothia-
zole, which was obtained1 earlier by the irradiation of 4f in
methanol, in the absence of benzophenone using MLR. The
structure of photoproduct 5f was confirmed by spectral and
analytical data.
A methanolic solution of triazole-3-thione 4a (0.3 g,
1 mmol), after flushing with nitrogen for 1 h, was irradiated
in multilamp reactor (254 nm). Even after 100 h of
irradiation, no reaction was observed. Next, thione 4a in
methanol containing 1.2 equiv. of benzophenone, was
flushed with N2 and irradiated using multilamp reactor for
62 h, to afford the desulfurized 3-phenyl-4-methylphenyl-
1,2,4-triazole 5a in good yield, (Scheme 6). A trace of sulfur
was also isolated along with the desulfurized product.
Likewise, irradiation of the triazole-3-thiones 4b–e in
methanol, also afforded the corresponding desulfurized
triazoles 5b–e in good yields (Table 5). The irradiation of
1a–d in the presence of benzophenone yielded the
respective desulfurized triazoles 3a–d, instead in an
experiment in the absence of benzophenone, thione 1a did
not give any product even after 100 h of irradiation. The
photoproducts 5a–e were confirmed by mp and mixture mp
and superimposable IR with those obtained under thin film
reaction (TFR) condition, which has been reported earlier.16
Likewise the photoproducts 3a–c were confirmed by mp,
mixture mp and superimposable IR with those obtained
under base mediated photolytic conditions. The structure of
3d was confirmed by spectral and analytical data.
Irradiation of 4g using MLR (100 h) did not afford any
product, but the starting triazole-3-thione in 82% yield.
However, the irradiation of 4g in the presence of
benzophenone (1.2 equiv.) in MLR for 65 h, furnished the
desulfurized product 3,4-di-(2-chlorophenyl)-1,2,4-triazole
5g in 60% yield.
The triazole-3-thione 4a (no o-halogen in the 4-aryl ring)
and 4-(2-chlorobenzyl)-5-phenyl-1,2,4-triazole-3-thione 1a
in methanol, do not undergo any photochemical reaction in
MLR (254 nm) in the absence of benzophenone. Whereas,
the photolysis of these thiones in the presence of
benzophenone, which is a well-known triplet sensitizer
(ET¼69 kcal/mol) produced desulfurized triazole in MLR
Table 4. The various substituted 1,2,4-triazole-3-thiones 4a–g
Compound 4a–g
R1
R2
4a
4b
4c
4d
4e
4f
Phenyl
p-Tolyl
o-Tolyl
4-Pyridyl
Phenyl
Phenyl
p-Tolyl
p-Tolyl
1-Naphthyl
p-Tolyl
Benzyl
o-Chlorophenyl
o-Chlorophenyl
4g
o-Chlorophenyl
Scheme 6.

A. Senthilvelan et al. / Tetrahedron 60 (2004) 851–860
Table 5. Photodesulfurization of triazole-3-thiones using multilamp reactors (MLR)
855
Starting compound
R1
R2
Product
Reaction time (h)
Yield (%)
4a
4b
4c
4d
4e
4f
4g
1a
1b
1c
1d
Phenyl
p-Tolyl
o-Tolyl
4-Pyridyl
Phenyl
Phenyl
2-Chloro phenyl
Phenyl
p-Tolyl
o-Anisyl
o-Tolyl
p-Tolyl
p-Tolyl
1-Naphthyl
p-Tolyl
Benzyl
2-Chloro phenyl
2-Chloro phenyl
2-Chloro benzyl
2-Chloro benzyl
2-Chloro benzyl
2-Bromo benzyl
5a
5b
5c
5d
5e
5f
5g
3a
3b
3c
3d
38
40
30
43
33
50
65
62
53
47
48
42
59
70
30
57
52
60
67
60
48
71
using methanol as a solvent. In this line, photolysis of 1b–d
and 4b–g also afforded the desulfurized triazole (Table 5),
in the presence of benzophenone.
Similarly, photolysis of a methanolic (180 mL) solution of
1a containing xanthone (1.2 equiv.) (ET¼74 kcal/mol), after
flushing with nitrogen, in MLR for 48 h also yielded
desulfurized triazole 3a in 75%yield.
To ensure the absorption of light exclusively by benzophe-
none, a longer wavelength experiment was carried out.
Photolysis of 1a in methanol (180 mL) containing benzo-
phenone (1.2 equiv.), after flushing with nitrogen, under
multilamp reactor with wave length 365 nm for 70 h, also
afforded the desulfurized triazole 3a, but in a slightly lower
yield (59%), when compared with the benzophenone
experiment (67% yield) at 254 nm. This indicates that
some reaction proceeds from the direct excitation of the
substrate [M] to S1, followed by ISC to T1, which will
undergo the reaction in the triplet state. The slightly higher
yield (75%) of the product, when xanthone with higher ET
was used, also supports the triplet state reaction for the
desulfurization.
Scheme 7.
In this postulated mechanism, the triplet state episulfide III
is formed initially through the thiol tautomer II (the thiol
form was confirmed by H NMR and IR of thione) by (i)
1
direct population of triplet state, under benzophenone
sensitized reaction (ii) population of singlet state followed
by triplet state, under base mediated condition. Then the
episulfide intermediate loses sulfur to give the triazole IV.
Photoinduced desulfurization of episulfide, and desulfuriza-
tion of indoline-2-thione to indole via-episulfide had been
reported.20,21 The episulfide intermediate III in the reaction
could not be confirmed. However, irradiation in a non-protic
solvent such as benzene containing 4a and benzophenone
(1.2 equiv.) using MLR for 27 h, furnished the respective
desulfurized product 5a.
From the above observations, we believe that photodesul-
furization of triazole-3-thiones using MLR, in presence of
benzophenone is a triplet state reaction. This was further
evidenced by quenching the triplet state with a triplet
quencher. For that, the photolysis of 1a was carried out in
methanol (180 mL) containing benzophenone (1.2 equiv.)
after flushing with oxygen for 1 h in MLR (254 nm). After
67 h of irradiation, chromatographic separation afforded
50% of recovered starting triazole-3-thione, in addition to a
trace of desulfurized triazole 3a. The formation of a trace
amount of the desulfurized product 3a could be due to
inefficient oxygen supply, since oxygen was not bubbled
throughout the reaction. From the above observations, it is
concluded that the desulfurization of triazole-3-thiones must
be a triplet state reaction.
3. Conclusions
The triazole-3-thiones 1a–g and 4a–g were synthesized
from the corresponding acid hydrazides and isothiocya-
nates. Irradiation of 4-(2-halobenzyl)-5-substituted-1,2,4-
triazole-3-thiones 1a–e under base mediated condition
afforded the respective 1,2,4-triazolo[3,4-b]-1,3(4H)-ben-
zothiazines 2a–e and desulfurized triazoles 3a–c depend-
ing on the concentration of the base employed. However,
photolysis of 1f,g afforded only the desulfurized triazoles
3f,g even under stronger basic condition (CH3CN/2 M
NaOH). Irradiation of triazole-3-thiones 1a–d and 4a–g,
using MLR in presence of benzophenone (triplet sensitizer)
furnished desulfurized triazoles 3a–d and 5a–g, exclu-
sively. A reasonable mechanism for the photocyclization
involving singlet state, and for the desulfurization of
triazole-3-thiones, in the triplet state via an episulfide
intermediate has been proposed.
The irradiation of thione in CH3CN/NaOH medium giving
cyclization product probably takes place in the singlet state
by electron transfer mechanism from the thioenolate anion.
On the other hand, the formation of desulfurization product
could be from the thiol itself in the conventional S0!S1!T1
pathway involving the triplet state of the thiol. A reasonable
mechanism for the formation of desulfurized triazole from
triazole-3-thione is represented in Scheme 7.

856
A. Senthilvelan et al. / Tetrahedron 60 (2004) 851–860
4. Experimental
for C16H14N3SCl (315.820): C, 60.84; H, 4.46; N, 13.30.
Found: C, 60.97; H, 4.75; N, 13.03. The structure of the
compound 1b was further confirmed by XRD.12
4.1. General
All the melting points are uncorrected. UV spectra were
recorded with Shimadzu 1601 spectrophotometer. IR
spectra were recorded on FTIR-8300 Shimadzu spectro-
4.1.3. 5-(p-Anisyl)-4-(2-chlorobenzyl)-1,2,4-triazole-3-
thione (1c). Treatment of 2-chlorobenzyl isothiocyanate
(1.3 g, 8.0 mmol) with p-anisic hydrazide (1.47 g,
8.0 mmol) in ethanol afforded the thiosemicarbazide,
which on refluxing in 10% K2CO3 for 7 h, furnished 1c.
Yield: 2.12 g (80%), colourless solid, mp 195–197 8C; UV
(lmax): 260 nm (CH3OH); IR (KBr): 3107, 2945, 2588,
1
photometer. H and 13C NMR spectra were recorded with
Brucker-DPX 200 (200 MHz) and Jeol-GSX 400
(400 MHz) instruments with TMS as internal standard
(chemical shift in d ppm). The mass spectra were recorded
with Jeol-JMS-DX 303 HF and GCMS QP 5000 Shimadzu
instruments. Chromatographic separations were done using
silica gel (ACME samples). Thin layer chromatography
(TLC) was performed using glass plates coated with silica
gel (ACME samples) of 0.25 mm thickness. Spots were
visualized using iodine vapour. The photochemical reac-
tions were carried out in quartz vessel of different capacity
in Applied Photophysics multilamp reactor (254, 365 nm,
12 lamps).
1608, 1515, 1350, 1257, 1174 cm21 1H NMR (CDCl3/
;
DMSO-d6, 400 MHz): d 3.79 (s, 3H, OCH3), 5.34 (s, 2H,
CH2), 6.86–7.62 (m, 8H, ArH), 13.91 (s, 1H, SH). 13C
NMR (CDCl3/DMSO-d6,100 MHz): d 44.74 (CH2), 54.49
(OCH3), 113.53, 116.96, 126.28, 126.42, 127.69, 128.10,
128.65, 129.96, 130.91, 131.97, 150.98, 160.46 (C–OCH3),
167.61 (CvS). MS: m/z (%)¼331 (Mþ, 6), 333 (Mþ2, 2),
296 (100), 281 (4), 265 (3), 163 (4), 133 (10), 125 (28), 89
(14), 77 (6). Anal. calcd for C16H14N3OSCl (331.820): C,
57.91; H, 4.25; N, 12.66. Found: C, 58.10; H, 4.43; N, 12.81.
4.1.1. Synthesis of substituted 1,2,4-triazole-3-thiones
1a–g 4-(2-chlorobenzyl)-5-phenyl-1,2,4-triazole-3-
thione (1a). A mixture of 2-chlorobenzyl isothiocyanate
(1.34 g, 7.4 mmol) and benzoic acid hydrazide (1 g,
7.4 mmol) in ethanol (75 mL) was refluxed on a water
bath for 2 h, to afford the corresponding thiosemicarbazide
upon cooling. The thiosemicarbazide thus obtained was
filtered, then it was refluxed in 10% K2CO3 for 6 h, cooled,
filtered and the filtrate washed with ether. The aqueous layer
was acidified with cold, dil. HCl. The separated solid was
filtered and washed with water to furnish thiazine 1a;
recrystallized from ethyl acetate. Yield: 1.69 g (76%),
colourless solid, mp 210–212 8C; UV (lmax): 260 nm
(CH3CN); IR (KBr): 3084, 2935, 2598, 1554, 1431, 1353,
1276 cm21; 1H NMR (CDCl3/DMSO-d6, 200 MHz): d 5.37
(s, 2H, CH2), 6.96–7.46 (m, 9H, ArH), 13.88 (s, 1H, SH).
13C NMR (CDCl3/DMSO-d6, 50 MHz): d 45.70, 125.86,
127.30, 127.40, 128.10, 129.00, 129.70, 130.90, 132.04,
132.94, 152.06 (CvN), 169.01 (CvS); 13C NMR-DEPT-
135 (CDCl3/DMSO-d6, 50 MHz) d 45.60 (CH2#), 127.30,
128.00, 128.90, 129.60, 130.80 (all CH). MS: m/z (%)¼301
(Mþ, 6), 303 (Mþ2, 2), 266 (100), 233 (2), 206 (2), 125
(26), 103 (14), 89 (12), 77 (8). Anal. calcd for C15H12N3SCl
(301.794): C, 59.69; H, 4.00; N, 13.92. Found: C, 59.80; H,
4.11; N, 14.01.
4.1.4. 4-(2-Bromobenzyl)-5-(o-tolyl)-1,2,4-triazole-3-
thione (1d). Refluxing a mixture of 2-bromobenzyl
isothiocyanate (1.7 g, 7.5 mmol) and o-toluic hydrazide
(1.2 g, 7.5 mmol) in ethanol yielded the thiosemicarbazide,
which on treatment with 10% K2CO3 for 8 h, furnished 1d.
Yield: 2.23 g (83%), colourless solid, mp 188–190 8C; UV
(lmax): 253 nm (CH3OH); IR (KBr): 3087, 2927, 2578,
1598, 1453, 1338, 1247 cm21; 1H NMR(CDCl3, 400 MHz):
d 2.07 (s, 3H, CH3), 5.25 (s, 2H, CH2), 6.95–7.42 (m, 8H,
ArH), 12.40 (s, 1H, SH). 13C NMR(CDCl3, 100 MHz); d
19.44 (CH3), 47.34 (CH2), 122.50, 124.55, 126.05, 127.63,
128.35, 129.27, 129.58, 130.76, 131.09, 132.67, 133.92,
138.27, 151.84, 168.18 (CvS). MS: m/z (%)¼359 (Mþ)(361-
trace), 280 (100), 171 (10), 169 (10), 163, (2), 117 (6), 89 (12),
77 (4). Anal. calcd for C16H14N3SBr (360.271): C, 53.34; H,
3.91; N, 11.66. Found: C, 53.57; H, 3.78; N, 11.82.
4.1.5. 5-Benzyl-4-(2-chlorobenzyl)-1,2,4-triazole-3-
thione (1e). The thione 1e was prepared by refluxing the
thiosemicarbazide, obtained from 2-chlorobenzyl isothio-
cyanate (1.83 g, 10 mmol) and benzyl hydrazide (1.5 g,
10 mmol), in 10% K2CO3 for 7 h. Yield: 2.29 g (73%),
colourless solid, mp 150–152 8C; UV (lmax): 256 nm
(CH3OH); IR (KBr): 3083, 2918, 1588, 1448, 1347,
1
1239 cm21; H NMR (CDCl3, 400 MHz): d 3.89 (s, 2H,
4.1.2. 4-(2-Chlorobenzyl)-5-(p-tolyl)-1,2,4-triazole-3-
thione (1b). The thiosemicarbazide obtained by the
treatment of 2-chlorobenzyl isothiocyanate (1.22 g,
6.6 mmol) and p-toluic hydrazide (1 g, 6.6 mmol), when
refluxed in 10% K2CO3 for 7 h, afforded 1b.Yield: 1.81 g
(87%), colourless solid, mp 166–168 8C; UV (lmax):
258 nm (CH3OH); IR (KBr): 3097, 2921, 2563, 1614,
CH2), 5.29 (s, 2H, CH2), 6.83 (d, J¼7.6 Hz, 1H, H6–ArH),
7.08–7.39 (m, 8H, ArH). 13C NMR (CDCl3, 100 MHz): d
32.03 (C–CH2), 44.27 (N–CH2), 127.15, 127.28, 127.57,
128.45, 128.85, 129.11, 129.63, 131.58, 132.10, 132.82,
151.66, 168.30. MS: m/z (%)¼315 (Mþ, 16), 317 (Mþ2, 6),
280 (100), 247 (8), 163 (10), 125 (80), 89 (12), 77 (4). Anal.
calcd for C16H14N3SCl (315.820): C, 60.84; H, 4.46; N,
13.30. Found: C, 61.10; H, 4.73; N, 13.12.
1446, 1348, 1225 cm21
;
1H NMR (CDCl3/DMSO-d6,
200 MHz): d 2.35 (s, 3H, CH3), 5.36 (s, 2H, CH2), 6.95–
7.42 (m, 8H, ArH), 13.77 (s, 1H, SH). 13C NMR (CDCl3/
DMSO-d6,50 MHz): d 21.6, 46.0, 123.1, 127.5, 128.2,
129.1, 129.9, 132.2, 141.4, 152.4 (CvN), 169.1 (CvS); 13C
NMR-DEPT-135 (CDCl3/DMSO-d6, 50 MHz): d 21.6
(CH3"), 45.9 (CH2#), 127.4, 128.1, 129.1, 129.8 (all CH).
MS: m/z (%)¼315 (Mþ, 5), 317 (Mþ2, 2), 280 (100), 247
(2), 125 (30), 117 (8), 102 (4), 89 (14), 77 (6). Anal. calcd
4.1.6. 4-(2-Chlorobenzyl)-5-(2-chlorophenyl)-1,2,4-tri-
azole-3-thione (1f). The thiosemicarbazide, obtained from
2-chlorobenzyl isothiocyanate (1.07 g, 5.8 mmol) and
o-chlorobenzhydrazide (1 g, 5.8 mmol), was refluxed in
10% K2CO3 for 8 h to afford 1f. Yield: 1.76 g (85%),
colourless solid, mp 190–192 8C; UV (lmax): 257 nm
(CH3OH); IR (KBr): 3085, 2948, 2598, 1607, 1437, 1338,

A. Senthilvelan et al. / Tetrahedron 60 (2004) 851–860
857
1249 cm21; 1H NMR (CDCl3/DMSO-d6 200 MHz): d 5.31
(s, 2H, CH2), 6.97–7.45 (m, 8H, ArH), 13.90 (s, 1H, SH).
13C NMR (CDCl3/DMSO-d6, 50 MHz): d 44.8, 125.5,
127.1, 128.7, 129.1, 129.3, 129.9, 131.7, 132.4, 132.7,
132.8, 134.4, 149.4, 168.5 (CvS). MS: m/z (%)¼335 (Mþ,
5), 337 (Mþ2, 3), 300 (100)[302, 38], 280 (10), 163 (4), 137
(12)[139, 4], 125 (44), 102 (12), 89 (20), 77 (8). Anal. calcd
for C15H11N3SCl2 (336.238): C, 53.85; H, 3.29; N, 12.49.
Found: C, 53.82; H, 3.41; N, 12.66.
204–206 8C; UV (lmax): 261, 243 nm (CH3OH); IR (KBr):
1593, 1473, 748 cm21; 1H NMR (CDCl3, 400 MHz): d 2.45
(s, 3H, CH3), 5.20 (s, 2H, CH2), 7.22–7.60 (m, 8H, ArH).
13C NMR (CDCl3, 100 MHz): d 21.44, 47.61, 123.32,
127.30, 127.89, 127.92, 128.51, 129.07, 129.44, 129.82,
130.20, 140.64, 147.55, 154.06. MS: m/z (%)¼279 (Mþ,
100), 278 (22), 263 (3), 207 (2), 161 (14), 135 (22), 134
(44), 121 (25), 117 (12), 116 (14), 108 (12), 102 (4), 90 (20),
89 (24), 77 (12). Anal. calcd for C16H13N3S (279.360): C,
68.78; H, 4.69; N, 15.04. Found: C, 68.49; H, 4.93; N, 15.25.
4.1.7. 4-(2-Bromobenzyl)-5-(2-chlorophenyl)-1,2,4-tria-
zole-3-thione (1g). Treatment of 2-bromobenzyl isothio-
cyanate (1.33 g, 5.8 mmol) with o-chloro benzhydrazide
(1 g, 5.8 mmol) in ethanol afforded the thiosemicarbazide,
which on refluxing in 10% K2CO3 for 7 h furnished 1g.
Yield: 1.71 g (78%), colourless solid, mp 182–184 8C; UV
(lmax): 257 nm (CH3OH); IR (KBr): 3097, 2948, 2578,
4.3.2. 4-(2-Chlorobenzyl)-3-(p-tolyl)-1,2,4-triazole (3b).
Yield: 0.021 g (8%), colourless solid, mp 130–132 8C; UV
(lmax): 236 nm (CH3OH); IR (KBr) 1603, 1517,
1
1473 cm21; H NMR (CDCl3, 400 MHz): d 2.40 (s, 3H,
CH3), 5.29 (s, 2H, CH2), 6.87 (d, J¼7.32 Hz, 1H, C6–ArH),
7.23–7.47 (m, 7H, ArH), 8.16 (s, 1H, C5–H). 13C NMR
(CDCl3, 100 MHz): d 21.39, 46.53, 123.47, 127.63, 128.38,
128.57, 129.67, 130.02, 130.06, 132.76, 132.84, 140.49
144.33 (C5–H), 154.50 (CvN). MS: m/z (%)¼283 (Mþ,
68)[285, Mþ2, 20], 248 (100), 166 (3), 165 (4), 138 (2), 131
(4), 125 (92)[127, 32], 117 (5), 116 (6), 104 (4), 103 (24), 90
(12), 89 (34), 77 (36). Anal. calcd for C16H14N3Cl
(283.754): C, 67.72; H, 4.97; N, 14.80. Found: C, 67.87;
H, 5.10; N, 15.02.
1612, 1436, 1332, 1238 cm21
;
1H NMR (CDCl3,
400 MHz); d 5.34 (s, 2H, CH2), 6.98–7.46 (m, 8H, ArH),
12.17 (s, 1H, SH). 13C NMR (CDCl3, 100 MHz); d 47.56,
122.65, 124.84, 127.00, 127.62, 128.74, 129.38, 130.02,
131.58, 132.51, 132.66, 133.75, 134.45, 149.93, 168.54
(CvS). MS, m/z (%)¼(379 (Mþ), 381-trace), 300
(100)[302, 33], 169 (16)[171, 14], 163 (6), 137 (14)[139,
6], 102 (14), 90 (38), 77 (10). Anal. calcd for C15H11N3-
SClBr (380.690): C, 47.32; H, 2.91; N, 11.03. Found: C,
47.60; H, 3.10; N, 11.28.
4.4. Irradiation of (1c)
4.2. Photochemical synthesis of substituted 1,2,4-triazolo
[3,4-b]-1,3-(4H)-benzothiazines 2a–e and desulfurized
1,2,4-triazoles 3a–d,f,g from thiones 1a–g
5-(p-Anisyl)-4-(2-chlorobenzyl)-1,2,4-triazole-3-thione 1c
(0.35 g, 1.1 mmol) in acetonitrile (150 mL) containing
2 M NaOH (30 mL) was irradiated using a multilamp
reactor (254 nm) for 20 h. Usual workup followed by
chromatographic separation furnished the respective tria-
zolo benzothiazine 2c and triazole 3c.
4.2.1. Irradiation of (1a). (i) An acetonitrile solution
(150 mL) of 4-(2-chlorobenzyl)-5-phenyl-1,2,4-triazole-3-
thione 1a (0.3 g, 0.9 mmol) containing 30 mL of aqueous
2 M NaOH was flushed with nitrogen for 1 h and irradiated
at 254 nm in an Applied Photophysics multilamp reactor
(MLR) for 18 h. After completion of the reaction, checked
by TLC, the solvent was removed under reduced pressure
from the two-phase mixture and it was extracted with ethyl
acetate. The ethyl acetate layer was separated; the aqueous
layer was neutralized with dil. HCl, and extracted with ethyl
acetate. The ethyl acetate portions were combined together,
evaporated and the residue obtained was chromatographed
over a column of silica gel; elution with ethyl acetate–
petroleum ether (1:1) furnished the photosubstituted
3-phenyl-1,2,4-triazolo [3,4-b]-1,3(4H)-benzothiazine 2a
(41%). In addition 4-(2-chlorobenzyl)-3-phenyl-1,2,4-tria-
zole 3a (10%) was obtained in the petroleum ether–ethyl
acetate (3:7) elusion. The spectral and analytical data of
compounds 2a and 3a were reported earlier.6
4.4.1. 3-(p-Anisyl)-1,2,4-triazolo-[3,4-b]-1,3(4H)-ben-
zothiazine (2c). Yield: 0.12 g (38%), colourless solid, mp
166–168 8C; UV (lmax): 260, 206 nm (CH3OH); IR (KBr):
;
1614, 1467, 1245, 1031, 746 cm21 1H NMR (CDCl3,
400 MHz): d 3.85 (s, 3H, OCH3), 5.42 (s, 2H, CH2), 6.95 (d,
J¼8.76 Hz, 2H, ArH), 7.26–7.40 (m, 4H, ArH), 8.00 (d,
J¼8.8 Hz, 2H, ArH). MS: m/z (%)¼295 (Mþ, 100), 294
(90), 279 (56), 223 (4), 161 (20), 135 (21), 134 (80), 133
(21), 121 (35), 108 (10), 102 (11), 90 (42), 89 (41), 77 (23).
Anal. calcd for C16H13N3SO (295.359): C, 65.06; H, 4.43;
N, 14.22. Found: C, 65.25; H, 4.68; N, 14.38.
4.4.2. 3-(p-Anisyl)-4-(2-chlorobenzyl)-1,2,4-triazole (3c).
Yield: 0.047 g (15%), colourless solid, mp 156–158 8C; UV
(lmax): 248 nm (CH3CN); IR (KBr): 1583, 1503, 1450,
1
1358, 1259 cm21; H NMR (CDCl3, 400 MHz): d 3.84 (s,
3H, OCH3), 5.28 (s, 2H, CH2), 6.87 (d, J¼7.8 Hz, 1H, C6–
ArH), 6.97 (m, 2H, ArH), 7.23–7.51 (m, 5H, ArH), 8.16 (s,
1H, C5–H). MS: m/z (%)¼299 (Mþ, 71)[301, Mþ2, 25],
264 (72), 236 (11), 221 (5), 131 (3), 165 (11), 125 (100), 127
(32), 104 (2), 103 (10), 90 (20), 89 (36), 77 (10). Anal. calcd
for C16H14N3ClO (299.754): C, 64.10; H, 4.70; N, 14.01.
Found: C, 64.37; H, 4.89; N, 14.20.
4.3. Irradiation of (1b)
Irradiation of an acetonitrile (150 mL) solution of 4-(2-
chlorobenzyl)-5-(p-tolyl)-1,2,4-triazole-3-thione 1b (0.3 g,
1.0 mmol) containing 2 M NaOH (30 mL), after flushing
with nitrogen, in multilamp reactor for 17 h, followed by
usual workup as mentioned above and chromatographic
separation afforded triazolo benzothiazine 2b and triazole 3b.
4.5. Irradiation of (1d)
4.3.1. 3-(p-Tolyl)-1,2,4-triazolo-[3,4-b]-1,3(4H)-ben-
zothiazine (2b). Yield: 0.12 g (47%), colourless solid, mp
4.5.1. 3-(o-Tolyl)-1,2,4-triazolo-[3,4-b]-1,3(4H)-ben-
zothiazine (2d). (i) Irradiation of an acetonitrile (150 mL)

858
A. Senthilvelan et al. / Tetrahedron 60 (2004) 851–860
solution of 4-(2-bromobenzyl)-5-(o-tolyl)-1,2,4-triazole-3-
thione 1d (0.3 g, 1.1 mmol) containing 2 M NaOH (30 mL)
in a multilamp reactor for 11 h, and chromatographic
separation afforded 2d. Yield: 0.15 g (50%), colourless
solid, mp 173–175 8C; UV (lmax): 259, 231 nm (CH3OH);
(30 mL), (after flushing with nitrogen) in multilamp reactor
for 13 h, followed by chromatographic separation afforded
triazole 3g. Yield: 0.13 g (48%), colourless solid, mp 128–
130 8C; UV (lmax): 267 nm (CH3OH); IR (KBr): 1601,
1
1591, 1447 cm21; H NMR (CDCl3, 400 MHz): d 5.13 (s,
IR (KBr): 1585, 1470, 746 cm21
;
1H NMR (CDCl3,
2H, CH2), 6.90 (dd, J¼7.32, 2.44 Hz, 1H, C6–ArH), 7.16–
7.56 (m, 7H, ArH), 8.22 (s, 1H, C5–H). 13C NMR (CDCl3,
100 MHz): d 49.01, 123.55, 126.36, 127.15, 127.97, 129.83,
130.00, 130.46, 131.93, 132.63, 133.37, 133.57, 134.31,
143.89 (C5–H), 152.13 (CvN). MS: m/z (%)¼347 (Mþ,
40), 349 (Mþ2, 53), 351 (Mþ4, 13), 268 (100) [270 (30)],
233 (4), 206 (4), 176 (12), 169 (75)[170 (74)], 137 (3), 131
(10), 104 (18), 103 (5), 90 (76), 89 (55), 77 (12). Anal. calcd
for C15H11N3ClBr (348.624): C, 51.67; H, 3.18; N, 12.05.
Found: C, 51.88; H, 3.40; N, 12.30.
400 MHz): d 2.63 (s, 3H, CH3), 5.46 (s, 2H, CH2), 7.25–
7.91 (m, 8H, ArH). 13C NMR (CDCl3, 100 MHz); d 21.67,
50.68, 125.72, 127.30, 128.04, 128.42, 128.65, 128.98,
129.44, 131.11, 137.07, 147.20, 151.65, 153.15. MS: m/z
(%)¼279 (Mþ, 100), 278 (10), 264 (4), 161 (3), 135 (20),
134 (16), 121 (52), 117 (14), 116 (15), 108 (5), 102, (2), 90
(14), 89(22), 77(14). Anal. calcdforC16H13N3S (279.360): C,
68.78; H, 4.69; N, 15.04. Found: C, 68.52; H, 4.97; N, 15.32.
4.6. Irradiation of (1e)
4.9. General procedure for the synthesis of substituted
1,2,4-triazole-3-thiones 4a–g
4.6.1. 3-Benzyl-1,2,4-triazolo-[3,4-b]-1,3(4H)-benzothia-
zine (2e). The compound 2e was obtained on irradiation
of 5-benzyl-4-(2-chlorobenzyl)-1,2,4-triazole-3-thione 1e
(0.25 g 0.8 mmol) in acetonitrile (150 mL) containing 2 M
NaOH (30 mL) using multilamp reactor for 21 h, followed
by chromatographic separation. Yield: 0.10 g (45%),
colourless solid, mp 162–164 8C; UV (lmax): 257, 208 nm
A mixture of acid hydrazide (1 equiv.) and aryl isothiocya-
nate (1 equiv.) was refluxed in K2CO3 solution (100 mL,
10%) for 6–8 h, cooled, filtered and the filtrate washed with
ether. The aqueous layer was neutralized with cold, dil. HCl
(in the case of 4d pH¼7 was maintained). The separated
solid was filtered and washed with water to get the
corresponding triazole-3-thione. The product was recrys-
tallized from ethyl acetate. The triazole-3-thione 4e was
prepared from the respective thiosemicarbazide, obtained
from the corresponding acid hydrazide and isothiocyanate.
(CH3OH); IR (KBr): 1595, 1475, 748 cm21 1H NMR
;
(CDCl3, 400 MHz): d 4.37 (s, 2H, CH2), 4.81 (s, 2H, CH2),
7.09–7.42 (m, 9H, ArH). 13C NMR (CDCl3, 100 MHz): d
31.45, 46.69, 127.39, 127.52, 127.89, 128.39, 129.17,
135.10, 147.50, 153.20. MS: m/z (%)¼279 (Mþ, 100), 278
(28), 161 (12), 135 (78), 134 (20), 121 (24), 117 (15), 116
(13), 108 (6), 102 (6), 90 (25), 89 (32), 77 (24). Anal. calcd
for C16H13N3S (279.360): C, 68.78; H, 4.69; N, 15.04.
Found: C, 68.98; H, 4.90; N, 15.30.
The spectral and analytical data for compounds 4a–e were
reported earlier.16
4.9.1. 4-(2-Chlorophenyl)-5-phenyl-1,2,4-triazole-3-
thione (4f). The thione 4f was prepared by refluxing a
mixture of 2-chlorophenyl isothiocyanate (1.0 g, 5 mmol)
and benzoic hydrazide 0.68 g (5 mmol) in 10% K2CO3 for
8 h. Yield: 1.03 g (72%), colourless solid, mp 224–226 8C
(lit.1 mp 222 8C).
4.7. Irradiation of 1f
4.7.1. 4-(2-Chlorobenzyl)-3-(2-chlorophenyl)-1,2,4-tria-
zole (3f). The irradiation of 4-(2-chlorobenzyl)-5-(2-chloro-
phenyl)-1,2,4-triazole-3-thione 1f (0.2 g, 0.6 mmol) in
acetonitrile (150 mL) containing 2 M NaOH (30 mL)
using multilamp reactor (254 nm) for 32 h, and usual
workup followed by chromatographic separation using
petroleum ether–ethyl acetate mixture (1:9) furnished the
respective triazole 3f. Yield: 0.085 g (47%), colourless
solid, mp 100–102 8C; UV (lmax): 267 nm (CH3OH); IR
4.9.2. 4,5-Di-(2-chlorophenyl)-1,2,4-triazole-3-thione
(4g). A mixture of 2-chlorobenzhydrazide (1.0 g, 5 mmol)
and 2-chlorophenyl isothiocyanate (1.0 g, 5 mmol) was
refluxed for 8 h in K2CO3 solution. Yield: 1.2 g (74%),
colourless solid, mp 252–254 8C; UV (lmax): 257 and 219 nm
(MeOH); IR (KBr): 3100, 2900, 2598, 1495, 1350, 1274,
(KBr): 1613, 1583, 1453 cm21
;
1H NMR (CDCl3,
1
400 MHz): d 5.12 (s, 2H, CH2), 6.88 (dd, J¼7.6, 1.6 Hz,
1H, C6–ArH), 7.14–7.50 (m, 7H, ArH), 8.25 (s, 1H, C5–
H). 13C NMR (CDCl3, 100 MHz): d 47.00, 126.55, 127.42,
127.62, 130.09, 130.27, 130.32, 130.60, 132.22, 132.86,
133.91, 134.58, 144.18 (C5–H), 152.45 (CvN). MS: m/z
(%)¼303 (Mþ, 38)[305, Mþ2, 22] [307, Mþ4, 8], 268
(68)[270, 30], 242 (4), 166 (4), 165 (3), 138 (6), 131 (5), 125
(100)[127, 30], 104 (30), 103 (8), 90 (14), 89 (33), 77 (12).
Anal. calcd for C15H11N3Cl2 (304.172): C, 59.22; H, 3.64;
N, 13.81. Found: C, 59.42; H, 3.83; N, 13.63.
1240 cm21; H NMR (CDCl3/200 MHz,): d 7.24–7.53 (m,
8H, ArH), 12.10 (s, 1H, SH). 13C NMR (CDCl3/50 MHz,): d
124.62, 125.67, 127.85, 128.40, 128.69, 129.01, 129.45,
129.88, 130.24, 130.53, 132.24, 147.48, 167.01; 13C NMR-
DEPT 90 (CDCl3/50 MHz,): d 124.63, 125.68, 127.86,
128.42, 128.68, 129.46, 129.88, 130.27 (all CH). MS: m/z
(%)¼321 (Mþ,13), (323, Mþ2), (325, Mþ4), 288 (40), 286
(100), 149 (90), 137 (5), 125 (11), 111 (11), 90 (11), 75 (18).
Anal. calcd for C14H9Cl2N3S (322.212): C, 52.18; H, 2.81; N,
13.04. Found: C, 52.09; H, 2.79; N, 13.08. The structure of the
compound 4g was further confirmed by XRD.17
4.8. Irradiation of 1g
4.10. General procedure for the photochemical
desulfurization of triazole-3-thiones 1a–d and 4a–g
4.8.1. 4-(2-Bromobenzyl)-3-(2-chlorophenyl)-1,2,4-tria-
zole (3g). Irradiation of an acetonitrile (150 mL) solution
of 4-(2-bromobenzyl)-5-(2-chlorophenyl)-1,2,4-triazole-3-
thione 1g (0.3 g, 0.8 mmol) containing 2 M NaOH
A methanolic solution (180 mL) of triazole-3-thione and
benzophenone (1.2 equiv.) was flushed with nitrogen for 1 h

A. Senthilvelan et al. / Tetrahedron 60 (2004) 851–860
859
and irradiated in a multilamp reactor (254 nm). After
completion of the reaction, checked by TLC, the solvent
was removed under reduced pressure. The residue obtained
was chromatographed over a column of silica gel. Elution
with petroleum ether–ethyl acetate afforded the desulfur-
ized triazoles.
236, 208 nm (MeOH); IR (KBr): 1524, 1434 cm21
;
1H
NMR (CDCl3, 400 MHz): d 7.25–7.60 (m, 9H, ArH), 8.30
(s, 1H, C5–H); 13C NMR (CDCl3, 100 MHz): d 126.24,
127.97, 128.18, 128.62, 129.01, 130.02, 130.97, 131.28,
131.67, 132.47, 144.62, (C5–H) 153.45 (CvN). MS: m/z
(%)¼255 (Mþ, 100)[257, Mþ2, 34], 254 (41)[256, 33], 220
(98), 193 (8), 166 (6), 165 (5), 152 (30)[154, 11], 138
(14)[140, 6], 125 (32)[127, 10], 103 (10), 90 (51), 89 (23),
77 (26). Anal. calcd for C14H10N3Cl (255.701): C, 65.76; H,
3.94; N, 16.43. Found: C, 65.97; H, 4.12; N, 16.71.
4.10.1. 3-Phenyl-4-(p-tolyl)-1,2,4-triazole (5a). Irradiation
of a solution of 4a (0.3 g, 1.1 mmol) and benzophenone
(0.24 g, 1.3 mmol) in methanol (180 mL) using MLR for
38 h, followed by chromatographic separation, afforded 5a.
Yield: 42%.
4.10.7.
3,4-Di-(2-chlorophenyl)-1,2,4-triazole
(5g).
Irradiation of 4,5-di-(2-chlorophenyl)-1,2,4-triazole-3-
thione 4g (0.25 g, 0.8 mmol) and benzophenone
(1.2 equiv., 0.17 g) in absolute methanol (180 mL), at
254 nm in MLR for 65 h, furnished 5g after chromato-
graphic separation. Yield: 0.12 g (60%), colourless solid,
mp 138–140 8C; UV (lmax): 268 and 222 nm (MeOH); IR
An ethanolic solution of 4a (0.5 g, 1.9 mmol) in the
presence of a catalytic amount of Raney Ni (in absolute
ethanol was refluxed for 23 h). After completion of the
reaction, the solution was filtered, concentrated and purified
over silica gel column to get 5a.Yield: 0.12 g, 47%, mp,
mixture mp and superimposable IR was found to be
consistent with 5a obtained from the photolysis of 4a.
1
(KBr): 1500 (CvN) cm21; H NMR (DMSO-d6/CD3CN/
200 MHz): d 7.30–7.50 (m, 8H, ArH), 8.75 (s, 1H). 13C
NMR (DMSO-d6/CD3CN/50 MHz): d 126.52, 127.71,
128.67, 129.84, 130.28, 130.96, 132.01, 132.75, 133.25,
134.28, 145.49 (C5–CH); 13C NMR-DEPT-135, (DMSO-
d6/CD3CN/50 MHz): d 127.71, 128.67, 129.84, 130.28,
130.95, 132.01, 132.76, 133.25, 145.49 (C5–CH) (all CH).
MS: m/z (%)¼289 (Mþ, 25), (291, Mþ2), (293, Mþ4), 254
(41), 256 (23) 152 (37), 138 (13), 125 (44), 111 (35), 90
(62), 75 (100), 63 (70), 50 (45). Anal. calcd for C14H9Cl2N3
(290.146): C, 57.95; H, 3.12; N, 14.48. Found: C, 58.05; H,
3.25; N, 14.38.
4.10.2. 3,4-Di-(p-tolyl)-1,2,4-triazole (5b). A solution of
4b (0.4 g, 1.4 mmol) and benzophenone (0.31 g, 1.7 mmol)
in methanol (180 mL) was irradiated using MLR for 40 h.
After completion of the reaction, followed by chromato-
graphic separation afforded 5b. Yield: 59%.
The thione 4b (0.6 g, 2.1 mmol) in 17% aq.HNO3 (50 mL)
was refluxed for 5 h. After completion of the reaction, it was
cooled to room temperature and then neutralized with dil.
NaOH. The solid obtained was filtered, washed with water
and recrystallized from ethyl acetate to isolate the
desulfurized product (0.29 g, 55%), which was compared
with the desulfurized triazole 5b, obtained under photolytic
condition by mp, mixture mp and superimposable IR.
A solution of 4g (0.5 g, 1.5 mmol) and catalytic amount of
Raney Ni in absolute ethanol was refluxed for 26 h. After
completion of the reaction, the solution was filtered,
concentrated and purified over silica gel column to get 5g.
Yield: 0.1 g, 22%, mp, mixture mp and superimposable IR
was found to be consistent with 5g obtained from the
photolysis of 4g.
4.10.3. 4-(1-Naphthyl)-3-(o-tolyl)-1,2,4-triazole (5c). Pho-
tolysis of 4c (0.3 g, 0.9 mmol) and benzophenone (0.2 g,
1.1 mmol) in methanol (180 mL) using MLR for 30 h,
followed by chromatographic separation, afforded 5c.
Yield: 70%.
4.10.8. 4-(2-Chlorobenzyl)-3-phenyl-1,2,4-triazole (3a).
A methanolic solution of 1a (0.3 g, 0.9 mmol) containing
benzophenone (0.12 g, 1 mmol) after flushing with nitrogen
was irradiated, in multilamp reactor for 62 h. After
completion of the reaction, chromatographic separation
afforded triazole 3a.
4.10.4.
3-(4-Pyridyl)-4-(p-tolyl)-1,2,4-triazole
(5d).
Irradiation of 4d (0.3 g, 1.1 mmol) and benzophenone
(0.24 g, 1.3 mmol) in methanol (180 mL) using MLR for
43 h, followed by chromatographic separation furnished 5d.
Yield: 30%.
4.10.9. 4-(2-Chlorobenzyl)-3-(p-tolyl)-1,2,4-triazole (3b).
Irradiation of a methanolic solution of 1b (0.4 g, 1.3 mmol)
and benzophenone (0.28 g, 1.5 mmol) using MLR for 53 h,
afforded 3b.
4.10.5. 4-Benzyl-3-phenyl-1,2,4-triazole (5e). Irradiation
of a mixture of 4e (0.3 g, 1.1 mmol) and benzophenone
(0.24 g, 1.3 mmol) in methanol (180 mL) using MLR for
33 h, furnished 5e. Yield: 57%.
4.10.10. 3-(p-Anisyl)-4-(2-chlorobenzyl)-1,2,4-triazole
(3c). Irradiation of a mixture of 1c (0.4 g, 1.2 mmol) and
benzophenone (0.26 g, 1.4 mmol) in methanol (180 mL)
using MLR for 47 h, furnished 3c. Yield: 48%.
The structures of triazoles 5a–e were confirmed by mp,
mixture mp and superimposable IR with those obtained
under TFR condition, which has been reported earlier.16
The structure of triazoles 3a–c were confirmed by mp,
mixture mp and superimpossable IR with those obtained
under base mediated photolytic condition.
4.10.6. 4-(2-Chlorophenyl)-3-phenyl-1,2,4-triazole (5f).
Photolysis of 4-(2-chlorophenyl)-5-phenyl-1,2,4-triazole-
3-thione 4f (0.25 g, 0.8 mmol) and benzophenone (0.19 g,
1.0 mmol) in methanol (180 mL) using MLR for 50 h,
followed by chromatographic separation, afforded 5f. Yield:
0.11 g (52%), colourless solid, mp 98–100 8C; UV (lmax):
4.10.11. 4-(2-Bromobenzyl)-3-(o-tolyl)-1,2,4-triazole
(3d). (ii) A methanolic solution (180 mL) of thione 1d
(0.2 g, 0.6 mmol) containing benzophenone (0.12 g,

860
A. Senthilvelan et al. / Tetrahedron 60 (2004) 851–860
3. Perioli, L.; Ambrogi, V.; Grandolini, G.; Giusti, L.; Lucacchini,
A.; Martini, C. I. L. Farmaco 1994, 49, 245–251.
4. Junnarkar, A. Y.; Singh, P. P.; Patnaik, G. K.; Shrotri, D. S.
Pharmacol. Res. 1992, 26, 131–141.
0.7 mmol) was flushed with nitrogen and irradiated in a
multilamp reactor for 48 h. After completion of the reaction
monitored by TLC, the solvent was removed under reduced
pressure; the residue obtained was chromatographed over a
column of silica gel. Elution with ethyl acetate afforded
desulfurized triazole 3d. Yield: 0.13 g (71%), colourless
solid, mp 108–110 8C; UV (lmax): 266 nm (CH3OH); IR
5. Grandolini, G.; Tiralti, M. C.; Rossai, C.; Ambrogi, V.;
Orzalesi, G.; De Regis, M. Farmaco [Sci.] 1987, 42, 43–60.
6. Grandolini, G.; Rossai, C.; Tiralti, M. C.; Orzalesi, G.; De
Regis, M. Farmaco [Sci.] 1985, 40, 221–236.
7. Senthilvelan, A.; Ramakrishnan, V. T. Tetrahedron Lett. 2002,
43, 5119–5121.
(KBr): 1602, 1581, 1462 cm21
;
1H NMR (CDCl3,
400 MHz): d 2.16 (s, 3H, CH3), 5.06 (s, 2H, CH2), 6.78
(d, J¼7.32 Hz, 1H, C6–ArH), 7.16–7.55 (m, 7H, ArH),
8.30 (s, 1H, C5–H). 13C NMR (CDCl3, 100 MHz); d 19.59,
48.57, 123.25, 125.83, 127.89, 129.61, 129.94, 130.27,
130.33, 130.62, 133.22, 133.69, 138.55, 143.56 (C5–H),
153.57 (CvN). MS: m/z (%)¼327 (Mþ, 15)[329, Mþ2,
16], 326[328], 312 (7), 248 (100), 172 (6), 169 (20)[171,
23], 158 (59), 131 (4), 117 (7), 116 (8), 104 (8), 103 (14), 90
(30), 89 (24), 77 (27). Anal. calcd for C16H14N3Br
(328.205): C, 58.55; H, 4.29; N, 12.80. Found: C, 58.80;
H, 4.41; N, 12.93.
8. Iqbal, R.; Rama, N. H.; Ahmed, N.; Zamani, K.; Ebrahim, S.;
Iqbal, N. Indian J. Chem. 1998, 37B, 506–509.
9. Dziewo n’ska, M. Spectrochim. Acta 1967, 23A, 1195–1204.
10. Horsfall, J. G.; Rich, S. Indian Phytopathol. 1953, 6, 1–10.
11. Levy, C. G.; Lichter, R. L.; Nelson, G. L. Carbon-13 nuclear
magnetic resonance spectroscopy. Wiley: New York, 1980;
p 165.
12. Rajakannan, V.; Senthilvelan, A.; Ramakrishnan, V. T.;
Velmurugan, D. Cryst. Res. Technol. (Under communication)
(Code no: CCDC 217654)..
13. Depuy, C. H.; Chapman, O. L. Molecular reactions and
photochemistry. Prentice-Hall of India: New Delhi, 1998; p 35.
14. Horspool, W. H.; Song, P. S. CRC handbook of organic
photochemistry and photobiology. CRC: New York, 1995;
p 250.
Acknowledgements
We wish to thank the University Grants Commission-
Special Assistance Program for financial assistance to the
Department of Organic Chemistry and CSIR for providing
research fellowship (A.S.V). We thank Dr E. J. Padma
Malar, Department of Physical Chemistry, University of
Madras, for helpful discussions.
15. Park, Y. T.; Jung, C. H.; Kim, K. W.; Kim, S. H. J. Org. Chem.
1999, 64, 8546–8556.
16. Senthilvelan, A.; Ramakrishnan, V. T. Heteroat. Chem. 2003,
14, 269–272.
17. Chinnakali, K.; Fun, H. K.; Senthilvelan, A.; Ramakrishnan,
V. T. Acta Crystallogr. 1999, C55. IUC9900005.
18. Surendranath, T. G.; Husain, S.; Srinivasan, V. R. Indian
J. Chem. 1977, 15B, 341–347.
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