Lewis acid / Base-free Strategy for the Synthesis of 2-Arylthio and Selenyl Benzothiazole / Thiazole and Imidazole

Article abstract of DOI:10.1515/hc-2020-0119

A Cu(II)-catalyzed Csp2-Se and Csp2-Sulfur bond formation was achieved with moderate to good yields without the aid of Lewis acid and base. The reaction is compatible with a wide range of heterocycles such as benzothiazole, thiazole, and imidazole. Also, this typical protocol is found to be active in thio-selenation via S-H activation. Additionally, we proposed a plausible mechanistic pathway involving Cu(III) putative intermediate.

Full text of DOI:10.1515/hc-2020-0119

Heterocycl. Commun. 2021; 27: 17–23
Research article
Open Access
Guniganti Balakishan, Gullapalli Kumaraswamy*, Vykunthapu Narayanarao and
Pagilla Shankaraiah
Lewis acid / Base-free Strategy for the Synthesis
of 2-Arylthio and Selenyl Benzothiazole /
Thiazole and Imidazole
https://doi.org/10.1515/hc-2020-0119
Received January 27, 2020; accepted January 27, 2021.
ideal process. Also, this strategy represents an extre-
mely attractive and competent route for the substitution
of C−H bond. Moreover, the strategy is considered to be
straightforward and has a step-economic advantage
than traditional reactions [17-18]. Primarily, this process
was induced by a sub-stoichiometric transition metal in
combination with additives and bases. This regioselec-
tive oxidative coupling strategy enabled the synthesis of
various pharmaceutically active heterocyclic molecular
motifs [19-21]. Various groups have reported the cross-
coupling of C−H bonds adjacent to a nitrogen atom to give
new C−C, C-X (X = S, Se, and Te) bond containing mole-
cules. In particular, the construction of new C−S and C-Se
bonds via oxidative functionalization of a C(sp2)-H bond
of benzothiazoles, thiazoles, benzoxazoles, azoles, ben-
zimidazole, imidazole, and oxadiazole has been repor-
ted elegantly [22-29]. Amongst such strategies, a Lewis
Abstract: A Cu(II)-catalyzed Csp2-Se and Csp2-Sulfur
bond formation was achieved with moderate to good
yields without the aid of Lewis acid and base. The reaction
is compatible with a wide range of heterocycles such as
benzothiazole, thiazole, and imidazole. Also, this typical
protocol is found to be active in thio-selenation via S-H
activation. Additionally, we proposed a plausible mecha-
nistic pathway involving Cu(III) putative intermediate.
Keywords: Selenation, thiolation, diphenyl diselenide,
thioaryl and selenoaryl derivatives, chalcogenide
Introduction
Organoselenium scaffolds engrossed much attention acid-catalyzed, stoichiometric Cu(II)-mediated thiolation
from chemists owing to their varied pharmaceutical acti- reaction between heteroarenes and thiols strategy offers
vity such as antioxidants [1-5], anti-inflammatory [6-8], an appealing alternative to the conventional methods [30]
and antimicrobial agents [9]. Additionally, the organose- (Scheme 1).
lenium molecular entities were assessed for anticancer
However, all these methods require stoichiometric
[10-11], neuroprotective [12], and antiviral properties amounts of external oxidants and bases. Hence, there
[13-14]. Recently, selenium-containing molecules have is still a great need for the development of sole oxidant
gained a great deal of significance due to the optical acti- as air and base free protocol to produce various thioaryl
vities of organic materials [15-16].
and selenoaryl derivatives of benzothiazoles, thiazoles,
The functionalization of C−H bonds adjacent to a azoles, benzimidazole, and imidazole.
hetero-atom utilizing cross-coupling is a conceptually
Results and discussion
In our continuous interest in developing base-free Cu cata-
lyzed reactions [31-34], we assessed the direct selenation
and thiolation of benzothiazole. Initially, conducting the
reaction between benzothiazole 1a (1 equiv.) and diphe-
nyl diselenide 2a (1.2 equiv.) in the presence of Cu(OAc)2
(100 mol%) and heating 100 °C in 1,4-dioxane resulted in
the desired product 3a at a 54% yield (Table 1, Entry 1).
When the catalyst loading reduced to 50 mol%, the same
*Corresponding author: Gullapalli Kumaraswamy, Organic
Synthesis &Process Chemistry Division, CSIR – Indian Institute
of Chemical Technology, Hyderabad – 500 007, India; Academy
of Scientific and Innovative Research (AcSIR), 2 Rafi Marg,
New Delhi – 110 001, India; E-mail: gkswamy_iict@yahoo.co.in
Guniganti Balakishan and Vykunthapu Narayanarao, Organic
Synthesis &Process Chemistry Division, CSIR – Indian Institute of
Chemical Technology, Hyderabad – 500 007, India
Pagilla Shankaraiah, Deparment of Chemistry, Osmania University,
Hyderabad-500 007, India
Open Access. © 2021 Balakishan et al., published by De Gruyter.ꢀ
Attribution alone 4.0 License.
ꢀThis work is licensed under the Creative Commons

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18ꢁ
Balakishan et al.: Lewis acid / Base-free Strategy
Previous work:
This work:
Scheme 1ꢀPrevious routs for selenation and thiolation of C−H bonds adjacent to a hetero-atom
reaction under otherwise identical condition gave the albeit inferior yield (Table 1, Entry 11). A screening of
product 3a in 70% yield (Table 1, Entry 2).
copper salts indicated that Cu(OAc)2.H2O performed with
In another reaction, the increased yield of 3a was good efficiency for this transformation, while CuI and
observed with 20 mol% of Cu(OAc)2 under the same set of CuOTf, CuCl2, and Cu(CH3CN)4PF6 led to inferior yields of
conditions (Table 1, Entry 3). A reaction with 10% Cu(OAc)2 3a (Table 1, Entries 11 to 15). The Co(OAc)2 and Pd(OAc)2
loading under typical conditions afforded 3a in a decrea- as catalyst failed to initiate the reaction (Table 1, Entries
sed yield (Table 1, Entry 4). Interestingly, it was observed 16-17). The reaction performed under an air balloon and
that the diphenyl diselenide 2a was not completely con- oxygen balloon gave 3a in trace amount. To demonst-
sumed (vide-supra) and the unreacted 2a was recovered rate the viability of this protocol, a scale-up reaction at
at a yield of 40%. When 2a molar ratio was reduced from 10 mmol levels had also been conducted and the desired
1.0 mmol to 0.6 mmol and carried out under identical con- product 3a was obtained with a similar yield.
ditions as above, this resulted in 3a with similar yields
Furthermore, the reaction scope was extended by
(Table 1, Entry 5). This result indicates that the by-product employing typical conditions and the results are shown
PhSeH re-oxidized to PhSeSePh under the atmosphere of in Table 2. To this end, N-methyl benzimidazole 1b and
air. Hence, it needs in an only half-molar equivalent. After N-ethyl benzimidazole 1c reacted in the presence of 2a
considerable experimentation, we established that benzo- using similar conditions. The expected products 3b and 3c
thiazole 1a (1 equiv.), diphenyl diselenide 2a (0.6 equiv.) were isolated in 87% and 82% yields, respectively (Table 2,
and 20 mol% of Cu(OAc)2 in 1,4-dioxane at 100 °C for 5 h Entry 1). Likewise, N-methyl imidazole 1d and N-phenyl
was most effective set of conditions, yielding the 3a at imidazole 1e reacted smoothly in the presence of 2a under
yield of 86% (Table 1, Entry 5).
standard protocol and the corresponding products 3d and
Among the solvents tested, only 1,4-dioxane gave a 3e were isolated in 86% and 85% yields, correspondingly
better yield of the desired compound 3a while other sol- (Table 2, Entry 2). Remarkably, under optimized condi-
vents, such as ClCH2CH2Cl, CH3CN, DMF, DMSO, and H2O tions, the substrates 4-methyl thiazole 1f and 5-methyl-
gave a lower yield of 3a (Table 1, Entries 6 to 10). Interes- 4-vinylthiazole 1g showed good reactivity with 2a in the
tingly, the reaction proceeded without solvent but with presence of Cu(AcO)2 and provided the seleno derivatives

Balakishan et al.: Lewis acid / Base-free Strategyꢁ
ꢁ19
Table 1ꢀOptimization of reaction conditions for direct selenationa
for the preparation of organo-sulfur-selenium containing
heterocycles.
In light of this work, we now propose the following
mechanism (Scheme 2). At first, copper insertion leads to
the active intermediate A which activates benzothiazole
resulting in a Cu-thiolate complex and concomitant abs-
traction of a C-H by releasing AcOH and the copper (II)
complex B. The copper (II) complex of B undergoes oxi-
dation via disproportion to form Cu(III)-complex C [35].
Then, reductive elimination of Cu(I)OAc liberates the
desired product. The Cu(I)OAc undergoes further oxida-
tion in the presence of air and AcOH to form copper(II)
acetate. A similar mechanistic pathway can be expected to
perform in the synthesis of sulfur-selenium heterocycles
of 5a-c. This hypothesis needs further study.
Entry
Catalyst
Solvent
3a (% yield)c
1
Cu(OAc)2 (100 mol%)
Cu(OAc)2 (50 mol%)
Cu(OAc)2 (20 mol%)
Cu(OAc)2 (10 mol%)
Cu(OAc)2 (20 mol%)
Cu(OAc)2 (20 mol%)
Cu(OAc)2 (20 mol%)
Cu(OAc)2 (20 mol%)
Cu(OAc)2 (20 mol%)
Cu(OAc)2 (20 mol%)
Cu(OAc)2 (20 mol%)
CuI(20 mol%)
CuOTf(20 mol%)
CuCl2 (20 mol%)
Cu(CH3CN)4PF6 (20 mol%)
Co(OAc)2 (20 mol%)
Pd(OAc)2 (20 mol%)
dioxane
dioxane
dioxane
dioxane
dioxane
(CH2Cl2)2
CH3CN
54
70
2
3
86
4
56
5
86b,d
40
6
7
60
8
DMF
35
9
DMSO
40
10
11
12
13
14
15
16
17
H2O
20
neat
40
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
20
25
Conclusion
20
30
In conclusion, this study may contribute to a refinement
of the cross-coupling of C−H bonds, in particular, adja-
cent to a nitrogen atom to give new C-X (X = S and Se)
bond containing molecules. Furthermore, the significant
practical advantage is circumventing the stoichiomet-
ric use of base and oxidant. This protocol provides an
alternative expedient synthesis of chalcogenide contai-
ning heterocyclic bioactive molecules. In particular, the
synthesis of sulfur-selenium heterocycles via oxidative
copper catalysis is the first of its kind to the best of our
knowledge. Further work is under progress towards this
end in our laboratory.
NRe
NRe
a) All reactions were carried out unless otherwise stated on the
1 mmol scale with 1.0 equiv. 1a and 1.1 equiv. of 2a in 2 mL of
dioxane heating at 100 °C for 5 h in the open air.
b) The reaction was carried out with 1.0 equiv. 1a and 0.6 equiv. of 2a.
c) Isolated yield but not optimized. Yields based on the disappea-
rance of 2a.
d) This reaction was also carried out at 10 mmol scale.
e) NR = No reaction.
3f and 3g, in the same way (Table 2, Entries 3 and 4). The
significant aspect of the reaction under this oxidative
condition is that it sustains a vinyl functionality (Table 2,
Entry 4). Furthermore, the direct thiolation protocol was Experimental Section
also achieved using typical selenation conditions. Then,
benzothiazole 1a, N-methyl benzimidazole 1b, 4-methyl All reactions were conducted under an open-air atmosphere.
thiazole 1h and 2-phenyl-1, 3, 4-oxadiazole were subjec- Apparatus used for reactions are oven-dried. 1,4-dioxane
1
ted to direct thiolation protocol using 2b. As expected, and other solvents were used as received. H-NMR spectra
the thiolation products 3h-k were furnished in good to were recorded at 300, 400 and 500 MHz and 13C-NMR at 75
high yields demonstrating the generality of this reaction and 125 MHz in CDCl3. J values were recorded in hertz and
(Table 2, Entries 5-8).
abbreviations used were s = singlet, d = doublet, m = multi-
Next, we intended to explore Cu-catalyzed S-H acti- plet, br = broad, dd = doublet of doublet. Chemical shifts (δ)
vation and trap the resulting organo-copper intermediate are reported relative to TMS (δ = 0.0) as an internal standard.
with diphenyl diselenide 2a under established protocol as IR (FT-IR) spectra were measured as KBr pellets or as films.
above. Under the typical procedure, the substrates 4a-c Mass spectral data were compiled using MS (ESI), HR-MS
were submitted for S-H activation. To our delight, all the mass spectrometers. Column chromatography was carried
substrates underwent reaction and the expected 2-phenyl- out using Silica gel 100–200 mesh (commercial suppliers).
selenothio derivatives 5a-c were isolated at a yield of 80%,
A typical procedure for the Synthesis of 2-phenyl-
70%, and 80%, respectively (Table 3, Entries 1-3). Interes- seleno benzothiozole (3a): Benzothizole 1a (1.0 mmol),
tingly, this method represents a novel and mild method diphenyl diselinide (0.6 mmol), and Cu(OAc)2.H2O (0.2 mmol,

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Balakishan et al.: Lewis acid / Base-free Strategy
Table 2ꢀCopper catalyzed synthesis of selenium and sulphur containing heterocycles
Entry
Substrate
Producta,b,c(%Yield)
Entry
Substrate
Producta,b,c(%Yield)
N
SePh
N
R
1
5
1b, R = Me
1c, R = Et
3b, R = Me (87%)
3c, R = Et (82%)
1a
3h (77%)
2
6
1d, R = Me
1e, R = Ph
3d, R = Me (86%)
3e, R = Ph (85%)
1b
3i (77%)
3
7
1f
3f (85%)
1h
1i
3j (78%)
3k (80%)
4
8
1g
3g (80%)
a) All reactions were carried out unless otherwise stated on the 1 mmol scale with 1.0 equiv. 1a-i and 0.6 equiv. of 2a and 2b in 2 mL of
dioxane heating at 100 °C for 5 h in the open air.
b) Isolated yield but not optimized. Yields based on the disappearance of 2a and 2b.
c) All products fully characterized by 1H-NMR, 13C-NMR, IR, and Mass.
20 mol%) were charged sequentially into a 10 mL round-bot- 8.2 Hz), 7.50-7.52 (m, 2H), 7.20-7.30 (m, 6H), 3.70 (s, 3H).
tomed flask. To this, 1,4-dioxane (5 mL) was added and the 13C-NMR (75MHz, CDCl3): δ 143.6, 142.7, 136.0, 132.4, 129.6,
resulting reaction mixture was stirred at 100 °C for 5 h. Then, 128.0, 123.4, 124.3, 122.5, 119.4, 109.5, 31.8. IR (KBr): 3019,
cooled to ambient temperature and the solvent was evapora- 1710, 1661, 1628, 1549, 1515, 1214, 742, 667, 627 cm-1. MS
ted to give a residue that was purified over silica gel column (ESI): 291 (M+H). HR-MS: Calculated for C14H12N2Se (M+H)
chromatography eluting with hexane / EtOAc (9:1) to give = 289.0238. Found (M+H) = 289.0231.
the desired product 3a (185 mg, 86%) as a yellow solid, mp.
Ethyl-2-(phenylselenyl)-1H-benzo(d)imidazole
°
°
1
38-40 C, lit. [22] 35-36 C. H-NMR (500MHz, CDCl3): δ 7.90 (3c) (Table 2, Entry 1): Dense liquid, yield 170 mg (82%).
(d, 1H, J = 8.2 Hz), 7.80 (d, 2H, J = 8.0 Hz), 7.70 (d, 1H, J = 1H-NMR (500MHz, CDCl3): δ 7.80-7.84 (m, 1H), 7.50-7.56
7.6 Hz), 7.40-7.50 (m, 4H), 7.26-7.29 (m, 1H). 13C-NMR (75MHz, (m, 2H), 7.20-7.31 (m, 6H), 4.32 (q, J = 7.3 Hz, 2H), 1.24
CDCl3): δ 162.7, 154.5, 136.6, 130.0, 129.9, 126.5, 125.9, 124.3, (t, J = 7.3 Hz, 3H). 13C-NMR (75MHz, CDCl3): δ 143.6, 142.9,
121.9, 120.7. IR (KBr): 3056, 2969, 2923, 2851, 1739, 1453, 135.1, 132.4, 129.6, 128.0, 123.2, 118.9.109.6, 40.6, 14.8. IR
1418, 1368, 1307, 1067, 1018, 968, 851, 737, 686 cm-1. MS (neat): 3055, 2977, 2927, 2852, 1609, 1576, 1414, 1343, 1251,
(ESI): 291 (M+H). HR-MS (m/z): Calculated for C19H19NSSe 1152, 1102, 1067, 1020, 772, 737, 688, 668 cm-1. MS (ESI):
(M+H) = 291.9684. Found (M+H) = 291.9693.
All other compounds including the sulfur-selenium 303.0395. Found = 303.0387.
303 (M+H). HR-MS: Calculated for C15H14N2Se (M+H) =
heterocycles were synthesized 1mmol scale employing
above typical procedure.
1-Methyl-2-(Phenylselenyl)-1H-imidazole (3d)
(Table 2, Entry 2): Yellow liquid, yield 250 mg (86%).
1-Methyl-2-(phenylselenyl)-1H-benzo(d)imidazole 1H-NMR (500MHz, CDCl3): δ 7.31-7.00 (m, 7H), 3.60 (s, 3H).
(3b) (Table 2, Entry 1): Yellow solid, yield 190 mg (87%), 13C-NMR (75MHz, CDCl3): δ 133.9, 130.5, 130.1, 129.3, 126.9,
°
1
mp. 58-62 C. H-NMR (500MHz, CDCl3): δ 7.80 (d, 1H, J = 123.7, 34.7. IR (neat): 2922, 2851, 1576, 1476, 1451, 1441, 1408,

Balakishan et al.: Lewis acid / Base-free Strategyꢁ
ꢁ21
1277, 1219, 1113, 1067, 1021, 913, 772, 687 cm-1. MS (ESI): 239 1078, 968, 772, 690 cm-1. MS (ESI): 301 (M+H). HR-MS: Cal-
(M+H). HR-MS: Calculated for C10H10N2Se (M+H) = 239.0082. culated for C15H12N2Se (M+H) = 301.9684. Found = 301.9693.
Found = 239.0077.
4-Methyl-2-(phenylselenyl)thiazole (3f) (Table 2,
1-Phenyl-2-(phenylselenyl)-1H-imidazole
(3e) Entry 3): Yellow liquid, yield 220 mg (85%). 1H-NMR
(Table2,Entry2):Yellowliquid,yield180mg(86%).1H-NMR (500MHz, CDCl3): δ 7.58-7.60 (m, 2H), 7.38-7.40 (m, 2H), 7.21
(500MHz, CDCl3): δ 7.40-7.10 (m, 12H). 13C-NMR(75MHz, (s, 1H), 6.70 (s,1H), 2.41 (s, 3H). 13C-NMR (75MHz, CDCl3):
CDCl3): δ 132.2, 130.9, 129.2, 128.1, 128.5, 127.4, 126.2. IR δ 156.3, 154.4 134.9, 132.0, 129.6, 129.0, 128.2, 116.6, 17.0. IR
(neat): 2921, 2852, 1730, 1597, 1498, 1458, 1422, 1300, 1219, (neat): 3019, 1710, 1661, 1628, 1549, 1515, 1214, 742, 667, 627
cm-1. MS (ESI): 256 (M+H). HR-MS: Calculated for C10H9NS
Se (M+H) = 256.0249. Found = 256.0250.
Table 3ꢀSynthesis of sulphur-selenium heterocycles via oxidative
copper catalysis
5-Methyl-2-(phenylselenyl)-4-vinylthiazole
(3g)
(Table 2, Entry 4): Yellow liquid, yield 180 mg (80%).
1H-NMR (500MHz, CDCl3): δ 7.69-7.70 (m, 2H), 7.31-7.40
(m, 2H), 7.2 (s, 1H), 6.6 (q, 1H, J = 11.3 Hz), 5.1 (q, 1H, J =
17.3 Hz), 2.38 (s, 3H). 13C-NMR (75MHz, CDCl3): δ 180.0,
136.0, 135.0, 135.0, 130.6, 130.3, 129.7, 129.2, 15.2. IR(neat):
2922, 2852, 1657, 1576, 1475, 1438, 1401, 1375, 1301, 1219,
1018, 999, 772,689 cm-1. MS (ESI): 282 (M+H). HR-MS: Cal-
culated for C12H11NSSe (M+H) = 282.1021. Found = 282.1017.
2-(Phenylthio)benzo(d)thiazole (3h) (Table 2,
Entry 5): Yellow liquid, Yield 140 mg (77%). 1H-NMR
(500MHz, CDCl3): δ 7.28 (t, 1H, J = 7.2 Hz), 7.55-7.40 (m, 4H),
7.66 (d, 1H, J = 8.3 Hz), 7.76 (d, 2H, J = 8.3 H), 7.90 (d, 1H, J =
8.2 Hz). 13C-NMR (75MHz, CDCl3): δ 169.4, 153.6, 135.1,
130.2, 129.7, 125.9, 124.1, 121.7, 120.6. IR(neat): 3019, 1710,
1661, 1628, 1549, 1515, 1214, 742, 667, 627 cm-1. MS (ESI): 244
(M+H). HR-MS: Calculated for C13H9NS2 (M+H) = 244.0249.
Found = 244.0244.
1-Methyl-2-(phenylthio)-1H-benzo(d)imidazole
(3i) (Table 2, Entry 6): Yellow liquid, yield 150 mg (82%).
1H-NMR (500MHz, CDCl3): δ 7.70 (d, 1H, J = 7.6 Hz), 7.20-
7.30 (m, 8H), 3.70 (s, 3H). 13C-NMR (75MHz, CDCl3): δ 142.0,
132.0, 130, 129.4, 129.0, 127.6, 23.2, 122.4, 119.8, 109.0, 30.7. IR
(neat): 3056, 2923, 2852, 1741, 1645, 1611, 1581, 1441, 1365,
1277, 1219, 1153, 1110, 1023, 1003, 818, 772, 688, 567 cm-1. MS
Entry
R
R-S-Se-Pha,b,c (Yield)
N
S
1
4a
5a (80%)
N
N
O
2
4b
5b (70%)
N
N
N
N
3
4c
5c (80%)
a) All reactions were carried out unless otherwise stated on the
1 mmol scale with 1.0 equiv. 4a-c and 0.6 equiv. of 2a in 2 mL of
dioxane heating at 100 °C for 5 h in the open air.
b) Isolated yield but not optimized. Yields based on the
disappearance of 2a.
c) All products fully characterized by 1H-NMR, 13C-NMR, IR, and Mass.
Scheme 2ꢀPlausible catalytic cycle for the direct selenation

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22ꢁ
Balakishan et al.: Lewis acid / Base-free Strategy
(ESI): 241 (M+H). HR-MS: Calculated for C14H12N2S (M+H) = Research funding:ꢀFinancial support was provided by
241.0794. Found = 241.0793.
the DST, New Delhi, India (Grant No: SR/S1/OC-08/2011).
4-Methyl-2-(phenylthio)thiazole (3j) (Table 2, Entry
1
7): Yellow liquid, yield 175 mg (78%). H-NMR (500MHz, Conflict of interest:ꢀAuthors state no conflict of interest.
CDCl3): δ 7.58-7.60 (m, 2H), 7.38-7.40 (m, 2H), 7.21 (s, 1H),
6.70 (s,1H), 2.41 (s, 3H). 13C-NMR (75MHz, CDCl3): δ 164.7, Data availability statement:ꢀAll data generated or ana-
153.5 133.5, 132.0, 129.6, 129.3, 115.0, 17.1. IR (neat): 3019.7, lyzed during this study are included in this published
1710, 1661.4, 1628, 1549, 1515.3, 1214.8, 742, 667, 627 cm-1. article and its supplementary information files.
MS (ESI): 208 (M+H). HR-MS: Calculated for C10H9NS2
(M+H) = 208.0249. Found = 208.0250.
2-Phenyl-5-(phenylthio)-1, 3, 4-oxadiazole (3k)
References
(Table 2, Entry 8): Yellow liquid, yield 140 mg (80%).
1H-NMR (500MHz, CDCl3): δ 7.97-7.90 (m, 2H), 7.69-7.60 (m,
[1] Jain VK. Chapter 1: An Overview of Organoselenium Chemistry:
2H), 7.50-7.40 (m, 6H). 13C-NMR (75MHz, CDCl3): δ 166.3,
From Fundamentals to Synthesis. In: Jain VK, Priyadarsini KI,
editors. Organoselenium Compounds in Biology and Medicine.
162.8, 133.6, 131.7, 129.7, 128.9, 126.7, 123.4. IR (neat): 3019,
Synthesis, Biological and Therapeutic Treatments. Royal
1710, 1661, 1628, 1549, 1515, 1214, 742, 667, 627 cm-1. MS (ESI):
Chemical Society; 2017. p. 1–33.
255 (M+H). HR-MS: Calculated for C14H10N2OS (M+H) =
255.9684. Found = 255.9693.
[2] Iwaoka M. Antioxidant Organoselenium Molecules. In: Santi C,
editor. Organoselenium Chemistry Between Synthesis and
Biochemistry. Bentham Science Publishers; p. 361-78.
[3] Sies H. Ebselen, a selenoorganic compound as glutathione
peroxidase mimic. Free Radic Biol Med. 1993 Mar;14(3):313–23.
[4] Nascimento V, Alberto EE, Tondo DW, Dambrowski D, Detty MR,
Nome F, et al. GPx-Like activity of selenides and selenoxides:
experimental evidence for the involvement of hydroxy
perhydroxy selenane as the active species. J Am Chem Soc.
2012 Jan;134(1):138–41.
2-((Phenylselanyl)thio)benzo(d)thiazole
(5a)
(Table 3, Entry 1): Yellow liquid, yield 155 mg (77%).
1H-NMR (500MHz, CDCl3): δ 7.90 (d, 1H, J = 8.2 Hz), 7.70 (d,
1H, J = 7.6 Hz), 7.50-7.61 (m, 2H), 7.24-7.28 (m,5H). 13C-NMR
(75MHz, CDCl3): δ 131.4, 129.8, 129.5, 129.1, 128.9, 127.6, 126.5,
125.2, 122.5, 121.2. IR (neat): 2956, 2918, 2850, 1727, 1462,
1426.3, 1377.8, 1265, 1123, 1077, 1003, 972, 909, 727, 687 cm-1.
MS (ESI): 323 (M+H). HR-MS: Calculated for C13H9NSeS2
(M+H) = 323.9414. Found = 323.9409.
[5] Nogueira CW, Zeni G, Rocha JB. Organoselenium and
organotellurium compounds: toxicology and pharmacology.
Chem Rev. 2004 Dec;104(12):6255–85.
2-Phenyl-5-((phenylselanyl)thio)-1,3,4-oxadiazole
(5b) (Table 3, Entry 2): Yellow liquid, Yield 160 mg (70%).
1H-NMR (500MHz, CDCl3): δ 7.90 (d, 1H, J = 7.5 Hz), 7.20-
7.61 (m, 9H). 13C-NMR (75MHz, CDCl3): δ 133.2, 132.0, 131.4,
129.5, 129.1, 127.6, 126.8. IR(neat): 2919, 2851, 1781, 1726,
1609, 1578, 1576, 1549, 1465, 1349, 1286, 1219, 1170, 1066,
1023, 956, 772, 689 cm-1. MS (ESI): 335 (M+H). HR-MS:
Calculated for C14H10N2OSSe (M+H) = 335.1021. Found =
335.1017.
1-Phenyl-5-((phenylselanyl)thio)-1H-tetrazole (5c)
(Table 3, Entry 3): Yellow liquid, yield 150 mg (80%).
1H-NMR (500MHz, CDCl3): δ 7.70 (d, 1H, J = 7.5 Hz), 7.60-7.20
(m, 9H). 13C-NMR (75MHz, CDCl3): δ 153.2, 150.9, 149.9, 149.2,
149.1, 149.0, 148.6 147.1, 144.0. IR (neat): 3019, 1710, 1661,
1628, 1549, 1515, 1214, 742, 667, 627 cm-1. MS (ESI): 334 (M+H).
HR-MS: Calculated for C13H10N4SSe (M+H) = 334.9864;
Found (M+H) = 334.9860.
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Supporting Information:ꢀCopies of 1H and 13C NMR
spectra are available.
Acknowledgements:ꢀORGIN program (CSIR) and CSIR
(New Delhi) is gratefully acknowledged for awarding the
fellowship to G. B and VN.

Balakishan et al.: Lewis acid / Base-free Strategyꢁ
ꢁ23
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