Eosin Y catalyzed visible-light-promoted one - Pot facile synthesis of 1,3,4- thiadiazole

Article abstract of DOI:10.5562/cca2520

A novel one-pot visible light irradiated synthesis of 1,3,4-thiadiazole from aldehydes and thioacyl hydrazides have been reported in presence of eosin Y as an organophotoredox catalyst at room temperature under aerobic condition. This synthesis includes a

Full text of DOI:10.5562/cca2520

CROATICA CHEMICA ACTA
CCACAA, ISSN 0011-1643, e-ISSN 1334-417X
Croat. Chem. Acta 88 (1) (2015) 59–65.
http://dx.doi.org/10.5562/cca2520
Original Scientific Article
Eosin Y Catalyzed Visible-light-promoted One –Pot Facile Synthesis of
1,3,4- Thiadiazole
Vishal Srivastava,a Pravin K. Singh,b and Praveen P. Singhc,
*
aLaboratory of Green Synthesis, Department of Chemistry, University of Allahabad, Allahabad – 211002, India
bFood Analysis and Research Lab, Centre of Food Technology, University of Allahabad, Allahabad – 211002, India
c Department of Chemistry, United College of Engineering & Research, Naini, Allahabad - 211010, India
RECEIVED JULY 23, 2014; REVISED DECEMBER 26, 2014; ACCEPTED JANUARY 9, 2015
Abstract. A novel one-pot visible light irradiated synthesis of 1,3,4-thiadiazole from aldehydes and
thioacyl hydrazides have been reported in presence of eosin Y as an organophotoredox catalyst at room
temperature under aerobic condition. This synthesis includes application of air and visible light as inex-
pensive, readily available, non-toxic and sustainable regents, which fulfils the basic principle of green
chemistry.
Keywords: Eosin Y, visible-light, organophotoredox, green chemistry, aerobic condition
INTRODUCTION
ing SET17−20 (single electron transfer). These organic
dyes have got much more attention with the last few
years also due to easy handling, eco-friendly and have
great potential for applications in visible-light-mediated
organic synthesis,21−24 which fulfils the basic principle
of green chemistry.
The five-membered heterocyclic compounds have
a great application and importance in heterocyclic
chemistry. Among them thiadiazole is a versatile moiety
that exhibits a wide variety of biological activities.
Thiadiazole moiety acts as “hydrogen binding domain”
and “two-electron donor system”. It also acts as a con-
strained pharmacophore. Many drugs containing thiadi-
azole nucleus are available in the market such as aceta-
zolamide, methazolamide, sulfamethazole, etc. 1,3,4-
thiadiazoles are associated with diverse pharmacologi-
cal activities such as analgesic,25 antidepressant, anxio-
lytic,26 anticonvulsant,27−28 anti-inflammatory,29 antim-
icrobial,30 anti-tubercular,31 antitumor,32 and anti-viral
activities.33
Sunlight is a unique and renewable natural source.1 The
development of methods to efficiently harness the solar
radiation energy has emerged as one of the central sci-
entific challenges of the twenty first century.2−3 There-
fore, some pioneering researchers have dedicated to
converting solar energy into chemical energy for chemi-
cal transformations.4−5 Recently, a surge of interest from
the synthetic community has brought photoredox mani-
folds to the forefront of catalysis. In this sequence visi-
ble light photoredox catalysis has recently received
much attention in organic synthesis owing to ready
availability, sustainability, non-toxicity and ease of
handling of visible light.6−11 In their revolutionary work
in this area, MacMillan,12 Yoon13 and Stephenson14−15
have used Ruthenium and Iridium complexes as the
photoredox catalyst, which has inspired the develop-
ment of several powerful methods for various chemical
transformations useful in organic synthesis.16
However, these transition metal based photocata-
lysts disadvantageously exhibit high cost, low sustain-
ability and potential toxicity. Recently, a superior alter-
native to transition metal photoredox catalysts, espe-
cially metal-free organic dyes such as eosin Y, fluo-
rescein, Rose Bengal, nile red, perylene and rhodamine
B have been used as economically and ecologically
superior surrogates for Ru(II) and Ir(II) complexes in
visible-light promoted organic transformations involv-
The synthesis of 1,3,4-thiadiazole have not been
reported by photooxidation reaction so far. Meanwhile
the aerobic oxygen has received a great importance in
research during present time.34−35 In general, organosul-
fur/nitrogen compounds have been frequently used as
precursors in radical reactions because they form radi-
cals very readily.36−38 Encouraged by organocatalytic
visible-light-mediated aerobic oxidative transforma-
tions39−40 and in continuation of our work on develop-
* Author to whom correspondence should be addressed. (E-mail: ppsingh23@gmail.com)

60
V. Srivastava et al., One-pot visible light irradiated synthesis of 1,3,4-thiadiazole
Scheme 1. Eosin Y catalysed visible light promoted synthesis of 1,3,4-thiadiazole.
ment of novel environmentally benign synthesis41−44
herein we report a simple, visible light irradiated, effi-
cient and green protocol for the synthesis of 1,3,4-
thiadiazoles, using eosin Y as photocatalyst with excel-
lent yield as depicted in Scheme 1.
7.65−7.74 (d, 2H, J = 8.1 Hz, 2´, 6´-ArH), 8.02−8.15 (d,
2H, J = 8.4 Hz, 3´, 5´-ArH), 13C NMR (75 MHz,
DMSO-d6) δ/ppm: 128.7, 128.9, 129.2, 129.3, 130.9,
131.6, 133.5, 134.3, 174.1; Anal. Calcd for C14H9ClN2S:
C, 61.65; H, 3.33; N, 10.27. Found: C, 61.42; H, 3.31;
N, 10.25.
EXPERIMENTAL
4b. 2-(3-chlorophenyl)-5-phenyl-1,3,4-thiadiazole
m.p. 187 ºC, m/z: 272.02; Mol. Wt: 272.75; H NMR
1
Melting points were determined by open glass capillary
method and are uncorrected. All chemicals used were
reagent grade and were used as received. H NMR and
(400 MHz, DMSO-d6) δ/ppm: 7.41−7.60 (m, 5H, ArH),
7.65−7.74 (dd, 1H, J = 8.1 Hz, J = 8.9 Hz, 5´-ArH),
7.80−7.85 (d, 1H, J = 8.1 Hz, 4´-ArH), 7.91−8.00 (d,
1
13C NMR spectra were recorded on a Bruker AVANCE
DPX (400 MHz and 75 MHz) FT spectrometer in
DMSO using TMS as an internal reference (chemical
shift in δ, ppm). Mass spectra were recorded on JEOL
SX-303 (FAB) mass spectrophotometer at 70ev. Ele-
mental analyses were carried out using a Coleman
automatic C,H,N analyser.
1H, J = 8.3 Hz, 6´-ArH), 8.04−8.13 (s, 1H, 2´-ArH), 13
C
NMR (75 MHz, DMSO-d6) δ/ppm: 127.4, 128.7, 128.8,
129.0, 129.2, 130.9, 133.5, 134.8, 134.9, 174.1; Anal.
Calcd for C14H9ClN2S: C, 61.65; H, 3.33; N, 10.27.
Found: C, 61.42; H, 3.31; N, 10.25.
4c. 2-(2-chlorophenyl)-5-phenyl-1,3,4-thiadiazole
1
m.p. 195 ºC, m/z: 272.02; Mol. Wt: 272.75; H NMR
(400 MHz, DMSO-d6) δ/ppm: 7.41−7.60 (m, 7H, ArH,
4´, 5´- ArH), 7.65−7.70 (d, 1H, J = 8.1 Hz, 3´-ArH),
7.73−7.78 (d, 1H, J = 8.1 Hz, 6´-ArH), 13C NMR (75
MHz, DMSO-d6) δ/ppm: 127.3, 128.7, 128.9, 129.2,
129.3, 130.1, 130.9, 132.2, 133.5, 136.9, 174.1; Anal.
Calcd for C14H9ClN2S: C, 61.65; H, 3.33; N, 10.27.
Found: C, 61.42; H, 3.31; N, 10.25.
General Procedure for the Synthesis of 2,5-disubsti-
tuted 1,3,4-thiadiazole 4(a−n):
A solution of an aldehyde 1(a−n) (1.0 mmol) and an
thioacylhydrazide 2(a−n) (1.0 mmol) in MeCN (3 mL)
was heated at 65 °C for 2−6 h to form the corresponding
thioacylhydrazone (as monitored by TLC). Then, eosin
Y (2.0 mol%) and TMP (2.0 equiv.) were added and the
mixture was irradiated with green LEDs (2.4 W, 120
lm) with stirring under an air atmosphere at rt for 10−18
h. After completion of the reaction (monitored by TLC),
water (5 mL) was added and the mixture was extracted
with EtOAc (3 × 5 mL). The combined organic phase
was dried over MgSO4, filtered and evaporated under
reduced pressure. The resulting product was purified by
silica gel column chromatography using a gradient mix-
ture of hexane/ethyl acetate as eluent to afford an ana-
lytically pure sample of 4(a−n). All the products are
known compounds and were characterized by the com-
parison of their spectral data with those reported in the
4d. 2-(4-methoxyphenyl)-5-phenyl-1,3,4-thiadiazole
1
m.p. 215 ºC, m/z: 268.07; Mol. Wt: 268.33; H NMR
(400 MHz, DMSO-d6) δ/ppm: 3.83 (s, 3H, -OCH3),
7.41−7.50 (m, 5H, ArH), 7.58−7.69 (d, 2H, J = 8.1 Hz,
3´, 5´-ArH), 8.05−8.13 (d, 2H, J = 8.4 Hz, 2´, 6´- ArH),
13C NMR (75 MHz, DMSO-d6) δ/ppm: 55.8, 114.8,
125.8, 128.5, 128.7, 129.2, 130.9, 133.5, 160.6, 174.1;
Anal. Calcd for C15H12N2 OS: C, 67.14; H, 4.51; N,
10.44. Found: C, 67.12; H, 4.50; N, 10.40.
4e. 2,5-diphenyl-1,3,4-thiadiazole
m.p. 140 ºC, m/z: 238.06; Mol. Wt: 238.31; H NMR
1
(400 MHz, DMSO-d6) δ/ppm: 7.41−8.03 (m, 10H,
ArH), 13C NMR (75 MHz, DMSO-d6) δ/ppm: 128.7,
129.2, 130.9, 133.5, 174.1; Anal. Calcd for C14H10N2 S:
C, 70.56; H, 4.23; N, 11.76. Found: C, 67.12; H, 4.50;
N, 10.40.
1
literature. In the H NMR spectra, signal of respective
protons of newly synthesized compounds 4(a−n)
showed the peaks for -CH3, -OCH3 and aromatic pro-
tons.
4a. 2-(4-chlorophenyl)-5-phenyl-1,3,4-thiadiazole
m.p. 180 ºC, m/z: 272.02; Mol. Wt: 272.75; H NMR
4f. 2-(4-bromophenyl)-5-phenyl-1,3,4-thiadiazole
m.p. 250 ºC, m/z: 317.96; Mol. Wt: 317.20; H NMR
1
1
(400 MHz, DMSO-d6) δ/ppm: 7.41−7.60 (m, 5H, ArH),
(400 MHz, DMSO-d6) δ/ppm: 7.41−7.60 (m, 5H, ArH),
Croat. Chem. Acta 88 (2015) 59.

V. Srivastava et al., One-pot visible light irradiated synthesis of 1,3,4-thiadiazole
61
7.63−7.84 (d, 2H, J = 8.2 Hz, 2´, 6´-ArH), 8.00−8.13 (d,
2H, J = 8.5 Hz, 3´, 5´-ArH), 13C NMR (75 MHz,
DMSO-d6) δ/ppm: 123.1, 128.7, 129.2, 129.7, 130.9,
132.1, 132.5, 133.5, 174.1; Anal. Calcd for
C14H9BrN2S: C, 53.01; H, 2.86; N, 8.83. Found: C,
52.99; H, 2.84; N, 8.81.
N, 9.77. Found: C, 62.80; H, 3.85; N, 9.75.
4l. 2-(3-chlorophenyl)-5-(p-tolyl)-1,3,4-thiadiazole
1
m.p. 162 ºC, m/z: 286.03; Mol. Wt: 286.78; H NMR
(400 MHz, DMSO-d6) δ/ppm: 2.34 (s, 3H, -CH3),
7.29−7.38 (d, 2H, J = 7.8 Hz, 3´´, 5´´-ArH), 7.65−7.74
(d, 2H, J = 7.8 Hz, 2´´, 6´´-ArH), 7.77−7.84 (dd, 1H, J =
8.1 Hz, J = 8.9 Hz, 5´-ArH), 7.86−7.89 (d, 1H, J = 8.1
Hz, 4´-ArH), 7.91−8.00 (d, 1H, J = 8.3 Hz, 6´-ArH),
8.04−8.13 (s, 1H, 2´-ArH), 13C NMR (75 MHz, DMSO-
d6) δ/ppm: 21.3, 127.4, 128.8, 129.0, 129.5, 130.5,
131.7, 134.8, 134.9, 174.1; Anal. Calcd for
C15H11ClN2S: C, 62.82; H, 3.87; N, 9.77. Found: C,
62.80; H, 3.85; N, 9.75.
4g. 2-(3-bromophenyl)-5-phenyl-1,3,4-thiadiazole
1
m.p. 258 ºC, m/z: 317.96; Mol. Wt: 317.20; H NMR
(400 MHz, DMSO-d6) δ/ppm: 7.41−7.60 (m, 5H, ArH),
7.67−7.78 (d, 1H, J = 8.2 Hz, J = 8.7 Hz, 5´-ArH),
7.81−7.89 (d, 1H, J = 8.3 Hz, 4´-ArH), 7.90−8.02 (d,
1H, J = 8.1 Hz, 6´-ArH), 8.04−8.14 (s, 1H, 2´-ArH), 13
C
NMR (75 MHz, DMSO-d6) δ/ppm: 122.2, 128.1, 128.7,
129.2, 129.9, 130.9, 131.4, 133.1, 133.5, 135.7, 174.1;
Anal. Calcd for C14H9BrN2S: C, 53.01; H, 2.86; N, 8.83.
Found: C, 52.99; H, 2.84; N, 8.81.
4m. 2-(2-chlorophenyl)-5-(p-tolyl)-1,3,4-thiadiazole
1
m.p. 168 ºC, m/z: 286.03; Mol. Wt: 286.78; H NMR
(400 MHz, DMSO-d6) δ/ppm: 2.34 (s, 3H, -CH3),
7.29−7.38 (d, 2H, J = 7.8 Hz, 3´´, 5´´-ArH), 7.41−7.60
(m, 7H, ArH, 4´, 5´-ArH), 7.65−7.74 (d, 2H, J = 7.8 Hz,
2´´, 6´´-ArH), 7.75−7.84 (d, 1H, J = 8.2 Hz, 3´-ArH),
7.86−7.98 (d, 1H, J = 8.2 Hz, 6´-ArH), 13C NMR (75
MHz, DMSO-d6) δ/ppm: 21.3, 127.3, 127.4, 128.9,
129.3, 129.5, 130.1, 130.5, 131.7, 132.2, 136.9, 174.1;
Anal. Calcd for C15H11ClN2S: C, 62.82; H, 3.87; N,
9.77. Found: C, 62.80; H, 3.85; N, 9.75.
4h. 2-(4-nitrophenyl)-5-phenyl-1,3,4-thiadiazole
m.p. 230 ºC, m/z: 283.04; Mol. Wt: 283.31; H NMR
(400 MHz, DMSO-d6) δ/ppm: 7.41−7.60 (m, 5H, ArH),
7.70−7.94 (d, 2H, J = 8.1 Hz, 2´, 6´-ArH), 8.01−8.18 (d,
2H, J = 8.3 Hz, 3´, 5´-ArH), 13C NMR (75 MHz,
DMSO-d6) δ/ppm: 124.4, 128.4, 128.7, 129.2, 130.9,
1
133.5, 139.6,
147.9, 174.1; Anal. Calcd for
C14H9N3O2S: C, 59.35; H, 3.20; N, 14.83. Found: C,
59.31; H, 3.18; N, 14.81.
4n. 2-(4-methoxyphenyl)-5-(p-tolyl)-1,3,4-thiadiazole
1
4i. 2-(3-nitrophenyl)-5-phenyl-1,3,4-thiadiazole
m.p. 220 ºC, m/z: 282.08; Mol. Wt: 282.36; H NMR
1
m.p. 242 ºC, m/z: 283.04; Mol. Wt: 283.31; H NMR
(400 MHz, DMSO-d6) δ/ppm: 2.34 (s, 3H, -CH3), 3.83
(s, 3H, -OCH3), 7.29−7.38 (d, 2H, J = 7.8 Hz, 3´´, 5´´-
ArH), 7.58−7.69 (d, 2H, J = 8.1 Hz, 3´, 5´-ArH),
7.65−7.74 (d, 2H, J = 7.8 Hz, 2´´, 6´´-ArH), 8.05−8.13
(d, 2H, J = 8.4 Hz, 2´, 6´-ArH), 13C NMR (75 MHz,
DMSO-d6) δ/ppm: 21.3, 55.8, 114.8, 125.8, 127.4,
128.5, 129.5, 130.5, 131.7, 160.6, 174.1; Anal. Calcd
for C16H14N2 OS: C, 68.06; H, 5.00; N, 9.92. Found: C,
68.03; H, 4.98; N, 9.89.
(400 MHz, DMSO-d6) δ/ppm: 7.41−7.60 (m, 5H, ArH),
7.69−7.79 (d, 1H, J = 8.1 Hz, J = 8.7 Hz, 5´- ArH),
7.82−7.88 (d, 1H, J = 8.2 Hz, 4´- ArH), 7.90−8.03 (d,
1H, J = 8.2 Hz, 6´-ArH), 8.04−8.16 (s, 1H, 2´-ArH), 13
C
NMR (75 MHz, DMSO-d6) δ/ppm: 122.8, 123.9, 128.7,
129.2, 130.1, 130.9, 133.5, 134.4, 148.4, 174.1; Anal.
Calcd for C14H9N3O2S: C, 59.35; H, 3.20; N, 14.83.
Found: C, 59.31; H, 3.18; N, 14.81.
4j. 2-phenyl-5-(p-tolyl)-1,3,4-thiadiazole
m.p. 155 ºC, m/z: 252.07; Mol. Wt: 252.33; H NMR
1
RESULTS AND DISCUSSION
(400 MHz, DMSO-d6) δ/ppm: 2.34 (s, 3H, -CH3),
7.41−7.60 (m, 5H, ArH), 7.69−7.80 (d, 2H, J = 7.9 Hz,
3´,5´-ArH), 7.90−7.98 (d, 2H, J = 8.1 Hz, 2´,6´-ArH),
13C NMR (75 MHz, DMSO-d6) δ/ppm: 21.3, 127.4,
128.7, 129.2, 129.5, 130.5, 130.9, 131.7, 133.5, 174.1;
Anal. Calcd for C15H12N2S: C, 71.40; H, 4.79; N, 11.10.
Found: C, 71.38; H, 4.77; N, 11.08.
In order to work out the envisaged protocol, a key reac-
tion was conducted with thioacylhydrazone 3(a−n) in
MeCN containing 2 mol% of eosin Y under an air at-
mosphere (without air bubbling) by irradiation with
visible light (green light-emitting diodes (LEDs), λ
max= 535 nm) at rt. The reaction delivered the desired
2,5-disubtituted 1,3,4-thiadiazole 4(a−n) in 12 % iso-
lated yield after 24h (Table 1, entry 1). Following this
experiment, a series of control experiments were per-
formed, which indicates that an organic base is essential
to give the desired product with high yield (97 %) (Ta-
ble 1, entry 2) and TMP was found to be the best base
(Table 2, entry 2 versus 6, 7, 9). There was no product
formation or it was formed in traces in the absence (−)
of any one of the reagents/catalyst (Table 1, entries
4k. 2-(4-chlorophenyl)-5-(p-tolyl)-1,3,4-thiadiazole
1
m.p. 160 ºC, m/z: 286.03; Mol. Wt: 286.78; H NMR
(400 MHz, DMSO-d6) δ/ppm: 2.34 (s, 3H, -CH3),
7.29−7.38 (d, 2H, J = 7.8 Hz, 3´´, 5´´-ArH), 7.46−7.55
(d, 2H, J = 8.2 Hz, 3´, 5´-ArH), 7.65−7.74 (d, 2H, J =
7.8 Hz, 2´´, 6´´-ArH), 8.02−8.15 (d, 2H, J = 8.2 Hz, 2´,
6´-ArH), 13C NMR (75 MHz, DMSO-d6) δ/ppm: 21.3,
127.4, 128.9, 129.3, 129.5, 130.5, 131.6, 131.7, 134.3,
174.1; Anal. Calcd for C15H11ClN2S: C, 62.82; H, 3.87;
Croat. Chem. Acta 88 (2015) 59.

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V. Srivastava et al., One-pot visible light irradiated synthesis of 1,3,4-thiadiazole
Table 1. Screening and control experimentsa
Entry
Visible Light
Eosin Y
Air
+
Time / h
24
Yield / %b
12c
1
2
+
+
−
+
+
+
+
+
+
+
+
+
+
+
−
+
+
+
+
+
+
+
+
10
97
n.r.d
3
+
24
4
+
24
n.r.
5
−
24
n.r.
45e
6
+
10
7
N2
O2
+
24
trace
97
8
10
9
10
97f
10
+
10
60g
11
+
10
42h
aReaction conditions: thioacylhydrazone (1.0 mmol), eosin Y (2.0 mol%), TMP (2.0 equiv.), MeCN (3.0 mL), green LEDs 2.4W,
120 lm irradiation under an air atmosphere at rt.
bIsolated yield of the product (4a−n). n.r. = no reaction.
cThe reaction was conducted without TMP base in MeCN.
dThe reaction was carried out in the dark.
eThe reaction was carried out using 20 W CFL (compact fluorescent lamp).
fThe reaction was carried out with 3.0 equiv. of TMP.
gThe reaction was carried out 1.0 equiv. of TMP.
hThe reaction was carried out with 1.0 mol% of eosin Y.
Table 2. Optimization of reaction conditionsa
Entry
Eosin Y / mol %
Base
TMP
Solventc
MeCN
MeCN
MeCN
MeOH
EtOH
Time / h
10
Yield / %b
1
2
3
4
5
6
7
8
9
3
2
1
2
2
2
2
2
2
97
97
42
72
62
52
55
82
65
TMP
10
TMP
10
TMP
TMP
16
16
DBU
DABCO
TMP
MeCN
MeCN
DMSO
MeCN
16
16
10
Et3N
16
aReaction conditions: thioacylhydrazone (1.0 mmol), eosin Y (2.0 mol%), TMP (2.0 equiv.), MeCN (3.0 mL), green LEDs 2.4W,
120 lm irradiation under an air atmosphere at rt.
bIsolated yield of the product (4a−n).
Croat. Chem. Acta 88 (2015) 59.

V. Srivastava et al., One-pot visible light irradiated synthesis of 1,3,4-thiadiazole
63
Scheme 2. One-pot facile synthesis of 1,3,4-thiadizole directly from aldehyde and thioacylhydrazide.
3−5). The reaction did not proceed satisfactorily when a
household 20 W fluorescent lamp was used instead of
green LEDs (Table 1, entries 6 versus 2). Notably, the
same result was obtained on using O2 (balloon) instead
of an air atmosphere (Table 1, entry 8 versus 2),
whereas in the absence of any gas or under a nitrogen
atmo-sphere no product formation was detected (Table
1, entry 5, 7). These results establish that visible light,
base, photocatalyst and air all are essential (+) for the
reaction and support the photocatalytic model of the
reaction. Thiadiaazole exhibit various biological activi-
ties and has greater synthetic utility in medicinal chem-
istry. The use of novel one-pot visible light irradiated
synthesis using eosin Y as an organophotoredox cata-
lyst fullfill the basic need of green chemistry.
tion media. MeCN was the best solvent in terms of the
reaction time and yield (Table 2, entry 1), hence it was
used throughout the synthesis. When the amount of the
catalyst was decreased from 2 mol% to 1 mol%, the
yield of 4(a−n) considerably reduced (Table 2, entry 3),
but the use of 3 mol% of the catalyst did not affect the
yield (Table 2, entry 1).
Under the established reaction conditions in hand,
the reaction was tried in a one-pot procedure starting
directly from an aldehyde 1(a−n) and an thioacylhy-
drazide 2(a−n) to give the desired product 4( a−n) as
depicted in Scheme 2.
To our delight, it worked well and a number of
symmetrical and unsymmetrical 2, 5-disubstituted 1,3,4-
thiadiazoles were successfully synthesized starting di-
rectly from various aldehydes 1(a−n) and thioacylhy-
drazides 2(a−n) (Tables 3).
This clearly shows that the reaction is very mild
and applicable to aryl and alkyl, tolerates considerable
functional group variations like MeO, Br, Cl and NO2 in
Next, the reaction conditions were optimized with
respect to solvents and the catalyst used in the reaction.
In all the tested solvents (MeCN, DMSO, MeOH and
EtOH) the yield of 4a−n was >55 % (Table 2), which
indicates that the reaction is not very sensitive to reac-
Table 3. Eosin Y catalysed synthesis of 1,3,4-thiadizole
Entry
1
2
3
4
R1
R2
C6H5
C6H5
C6H5
C6H5
C6H5
Product
4a
4b
4c
4d
4e
Time / h
14
Yield / %
82
4-Cl.C6H4
3-Cl.C6H4
2-Cl.C6H4
4-OCH3.C6H4
C6H5
14
13
10
10
85
87
96
92
5
6
7
8
9
10
11
12
13
14
4-Br.C6H4
3-Br.C6H4
4-O2N.C6H4
3-O2N.C6H4
4-CH3.C6H4
4-Cl.C6H4
3-Cl.C6H4
2-Cl.C6H4
4-OCH3.C6H4
C6H5
C6H5
C6H5
C6H5
4f
14
14
18
18
10
12
12
11
85
86
78
84
96
83
86
89
4g
4h
4i
4j
4k
4l
C6H5
4-CH3.C6H4
4-CH3.C6H4
4-CH3.C6H4
4-CH3.C6H4
4m
4n
10
97
Croat. Chem. Acta 88 (2015) 59.

64
V. Srivastava et al., One-pot visible light irradiated synthesis of 1,3,4-thiadiazole
Scheme 3. Proposed mechanism for the visible light irradiated synthesis of 1,3,4-thiadiazole using eosin Y as photocatalyst.
the substrate, which results the desired product 4(a−n)
in good to excellent yields (78−97 %). However, alde-
hydes 1(a−n) and thioacylhydrazides 2(a−n) with an
electron-donating group on the aromatic ring appear to
react faster and afford marginally higher yields in com-
parison to those bearing an electron withdrawing group.
On the basis of the above observations and the lit-
procedure by using inexpensive eosin Y as a powerful
organophotoredox catalyst at rt. The reaction involves
visible light, a base and O2 (air) as a valuable reagents.
This synthetic pathway includes a superior visible light
promoted and Eosin Y organophotoredox catalysed
methodology, which is superior in comparison to all other
alternative synthetic methods for 1,3,4-thiadiazoles. This
synthesis widens the scope of substrates for visible light
photoredox reactions. The present methodology also
offers many advantages of green chemistry such as high
atom economy, reduced reaction time, one-pot consoli-
dated procedure and high efficiency.
erature precedents, a plausible mechanism involving
photoredox catalysis for the oxidative cyclization of
acylhydrazones is depicted in Scheme 3. On absorption
of visible light, the organophotoredox catalyst eosin Y
1
(EY) is excited to its singlet state EY* which through
inter system crossing (ISC) comes to its more stable
triplet state 3EY* and undergoes a single electron trans-
fer (SET). 3EY* may undergo both reductive and oxida-
Acknowledgements. We sincerely thank SAIF, CDRI, Luck-
now and IISc Banglaore for providing microanalyses and
spectra.
3
tive quenching.45−49 A SET from A to EY* generates
thioacyl radical B, which undergoes intramolecular
cyclization (5-endo-trig) to form C followed by attack
of O2  to give the product 4, successively. The forma-
tion of superoxide radical anion ( O2  ) during the reac-
tion was confirmed by the detection of the resulting
H2O2 using KI/starch indicator.50
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