An alternatively metal-free synthesis of 1,3,5-triazines or 1,2,4-thiadiazoles from benzyl chlorides and benzylamines mediated by elemental sulfur

Article abstract of DOI:10.1016/j.tetlet.2019.151289

An elemental sulfur mediated reaction of benzyl chlorides with benzylamines is developed, which allows the practical synthesis of valuable 1,3,5-triazines. This protocol that is metal free, ligand free, and uses inexpensive elemental sulfur as oxidant or raw material displays mild reaction conditions, a broad substrate scope and moderate to good yields. Moreover, the modified sulfur-mediated reaction system can also be used to synthesize 1,2,4-thiadiazoles, by simply switching the stoichiometry of sulfur powder from 0.75 equivalents to 5 equivalents.

Full text of DOI:10.1016/j.tetlet.2019.151289

Journal Pre-proofs
An alternatively metal-free synthesis of 1,3,5-triazines or 1,2,4-thiadiazoles
from benzyl chlorides and benzylamines mediated by elemental sulfur
Yurong Zhang, Yafei Liu, Jun Zhang, Ren Gu, Shiqing Han
PII:
S0040-4039(19)31069-X
https://doi.org/10.1016/j.tetlet.2019.151289
TETL 151289
DOI:
Reference:
Tetrahedron Letters
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Received Date:
Revised Date:
Accepted Date:
23 July 2019
15 September 2019
16 October 2019
Please cite this article as: Zhang, Y., Liu, Y., Zhang, J., Gu, R., Han, S., An alternatively metal-free synthesis of
1,3,5-triazines or 1,2,4-thiadiazoles from benzyl chlorides and benzylamines mediated by elemental sulfur,
Tetrahedron Letters (2019), doi: https://doi.org/10.1016/j.tetlet.2019.151289
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An alternatively metal-free synthesis of 1,3,5-
triazines or 1,2,4-thiadiazoles from benzyl
chlorides and benzylamines mediated by
elemental sulfur
Leave this area blank for abstract info.
Yurong Zhanga , Yafei Liua , Jun Zhanga , Ren Gua and Shiqing Hana,b 
R2
NH·HCl
N
S
R1
S
8 (0.75 equiv)
S
8 (5.0 equiv)
Cl
NH2
N
R2
+
N
N
R1
KOH, DMSO
Na2CO3, DMSO
R2
N
42%-75%
R1
R1
42%-88%

1
Tetrahedron Letters
journal homepage: www.elsevier.com
An alternatively metal-free synthesis of 1,3,5-triazines or 1,2,4-thiadiazoles from
benzyl chlorides and benzylamines mediated by elemental sulfur
Yurong Zhanga , Yafei Liua , Jun Zhanga , Ren Gua and Shiqing Hana,b 
a College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 211816, China
b Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, CAS, 345 Lingling Road, Shanghai 200032, China
———
ARTICLE INFO
ABSTRACT
* Corresponding author. Tel: +86-25-58139970; Fax: 86-25-58139369.
E-mail address:hanshiqing@njtech.edu.cn (S. Han).
Article history:
Received
An elemental sulfur mediated reaction of benzyl chlorides with benzylamines is developed,
which allows the practical synthesis of valuable 1,3,5-triazines. This protocol that is metal free,
Received in revised form
Accepted
Available online
ligand free, and uses inexpensive elemental sulfur as oxidant or raw material displays mild
reaction conditions, a broad substrate scope and moderate to good yields. Moreover, the
modified sulfur-mediated reaction system can also be used to synthesize 1,2,4-thiadiazoles, by
simply switching the stoichiometry of sulfur powder from 0.75 equivalents to 5 equivalnts.
Keywords:
1,3,5-Triazines
1,2,4-Thiadiazoles
Elemental sulfur
Synthetic method
2019 Elsevier Ltd. All rights reserved.
Introduction
amidines were frequently used as substrates to prepare 1,3,5-
triazines. For example, amidine hydrochlorides have been
In recent decades, elemental sulfur has attracted much
attention in organic synthesis since elemental sulfur exhibits non-
toxic, low-cost, abundant, and stable properties under normal
conditions. The elemental sulfur has been typically used as redox
reagent, catalyst, building unit and so on, which depends on its
numerous oxidation states, ranging from -2 to +6.1 For instance,
sulfur powder was reported to play an important role in the
construction of C-C and C-N bonds, both as starting oxidant and
reduced product.2
reported to react with aryl aldehydes to afford 1,3,5-triazines by
cyclodehydrogenation (Scheme 1a).7 Alternatively method for
the synthesis of 1,3,5-triazines was developed via ruthenium-
promoted oxidative condensation of primary alcohols and
amidines (Scheme 1b).8 However, the using of expensive catalyst
limited the further application of this method. Zhang and co-
workers further improved this method by using low cost copper
salt as catalyst under reflux conditions (Scheme 1b).9 After that, a
transition-metal free NIS-catalyzed oxidative cyclization of
primary alcohols with amidines to 1,3,5-triazines has been
employed by Bhanage and co-workers (Scheme 1b).10 Recently,
the method for synthesis of 1,3,5-triazines from benzylamines
and amidines by employing O2 as an oxidant has been reported
(Scheme 1c).11 Although those methods are efficiency, the
reported approaches to the synthesis of 1,3,5-triazines are still
rare in the literature. Therefore, developing an efficiency protocol
for the synthesis of 1,3,5-triazines is still necessary. In
continuation with our ongoing research in sulfur mediated
reactions,12 herein, we report a simple and efficient method for
the synthesis of 1,3,5-triazines mediated by elemental sulfur
(Scheme 1d), and the synthesis of 1,2,4-thiadiazoles via
alternating the reaction conditions.
O
N
H
N
N
S
N
N
N
N
S
H2N
N
NH
N+
N
O
N
N
N
N
N
N
O
H
2N
O
O-
NH2
Cyromazine
Altretamine
Cefozopran
Figure 1. Biologically active 1,3,5-triazines and 1,2,4-
thiadiazole
Nitrogen-containing heterocyclic compounds are privileged
motifs frequently found in pharmaceutical and biologically active
compounds.3 Among these compounds, 1,3,5-triazines have
attracted increasing attention since they are potentially scaffolds
for the construction of many biologically active compounds, such
as anticarcinogen, antiviral, and antibacterial.4 At present, 1,3,5-
triazines constitute the core units of many commercially drugs,
such as the Altretamine5a which is used in the treatment of
women with epithelial ovarian carcinoma, and Cyromazine5b can
be used as insect growth regulator (Figure 1).
Earlier, the general methods for the synthesis of 1,3,5-triazines
mainly relied on the cyclotrimerization of nitriles.6 Later,

2
Tetrahedron Letters
Previous work
O
(entries 1-3), and the 0.75 equiv of sulfur powder gave the
Ar1
product 3aa in 68% yield (entry 3). With further increasing of
sulfur powder from 0.75 to 1.0 equiv, the yield of 3aa was
decreased. And the yield of 3aa decreased to 41% in the absence
of elemental sulfur (entry 5). Then optimization focused on the
reaction temperature, changing the reaction temperatures to 120
°C or 140 °C both resulted the decreased yields of 3aa (entry 3 vs
entries 6-7). Furthermore, the influence of various bases and
solvent on the yields of product 3aa was investigated, which
showed that KOH was the best choice base (entry 10 vs entries 3,
8-9, 11-12) and DMSO was the best choice solvent(entry 10 vs
entries 13-15). Finally, changing the reaction time to 18 h or 36 h
both provided lower yields of 3aa (entry 10 vs entries 16-17).
Thus, the optimized reaction conditions for 1,3,5-triazines were
confirmed: benzamidine hydrochloride 1a (1.0 equiv , 0.5 mmol),
benzyl chloride 2a (1.0 equiv), sulfur powder (0.75 equiv) and
KOH (3.0 equiv) in DMSO (2.0 mL) at 130 °C for 24 h (entry
10).
NH·HCl
NH2
base
N
N
a
Ar1
H
+
Ar2
solvent
Ar2
N
Ar2
Ar1
NH·HCl
NH2
[Ru] or [Cu]
or
NIS
N
N
Ar1
OH
+
b
Ar2
base, solvent
Ar2
N
Ar2
Ar1
NH·HCl
NH2
O2
N
N
Ar1
NH2
+
Ar2
c
base, solvent
Ar2
N
Ar2
This work
Ar1
NH·HCl
NH2
S8
N
N
d
Ar1
Cl
+
Ar2
base, solvent
Ar2
N
Ar2
Scheme 1 Different routes for the synthesis of 1,3,5-triazines
from benzamidine hydrochlorides.
With the optimized reaction conditions in hand, an
investigation of the substrate scopes for the 1,3,5-triazines
formation was carried out. The results were summarized in Table
2. The benzyl chloride with various substituents at different
positions ranging from simple methyl (3ab, 3ag, 3al), methoxy
(3ah), tertiary butyl (3af) to halogens such as F (3ae, 3ak), Cl
Results and discussion
Considering that the benzyl chlorides could serve as carbon
sources to construct heterocycles under an oxidative system, we
chose benzamidine hydrochloride 1a (1.0 equiv, 0.5 mmol) and
benzyl chloride 2a (1.0 equiv) as the model substrates to
investigate the reaction conditions for construction of 1,3,5-
triazines (Table 1). The use of Na2CO3 (3.0 equiv) as the base
with sulfur powder (0.25 equiv) in dimethyl sulfoxide (DMSO)
(2.0 mL) at 130 °C for 24 h provided the 1,3,5-triazine 3aa in
Table 2 Substrate scopes for 1,3,5-triazines synthesisa
R2
NH·HCl
Cl
NH2
S8
R2
R1
N
N
DMSO, KOH
130 oC, 24 h
Table 1 Optimization of 1,3,5-triazine synthesisa
N
R1
2a-m
R1
1a-d
3
NH·HCl
NH2
OCH3
Cl
Cl
S8
N
N
conditions
N
N
N
N
N
N
N
N
N
1a
2a
3aa
N
N
N
N
3aa, 82%
3ab, 60%
3ac, trace
3ad,73%
F
tBu
Entry
S8
Base
Temp
(oC)
130
130
130
130
130
120
140
130
130
130
130
130
130
130
130
130
130
Solvent
Yieldb
(%)
45
50
68
61
41
56
66
55
78
82
56
69
65
34
11
OCH3
(equiv)
0.25
0.5
0.75
1
N
N
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16c
17d
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Cs2CO3
K2CO3
KOH
K3PO4
NaOH
KOH
KOH
KOH
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
Toluene
DMF
N
N
N
N
N
N
N
N
N
N
3ah, 62%
3ae, 79%
3af, 85%
3ag, 76%
Cl
Br
F
0
N
N
0.75
0.75
0.75
0.75
0.75
0.75
0.75
0.75
0.75
0.75
0.75
0.75
N
N
N
N
N
N
N
3ai, 73%
3ak, 79%
3aj, 88%
N
N
N
N
N
N
3al, 83%
3am, 42%
tBu
THF
DMSO
DMSO
N
N
N
N
N
N
N
N
N
KOH
KOH
72
60
Br
Br
F3
C
CF3
F3
C
CF3
3ba, 62%
3ca, 72%
3cf, 69%
a Reaction conditions: 1a (1.0 equiv, 0.5 mmol), 2a (1.0 equiv), sulfur powder
,
base (3.0 equiv), and DMSO (2.0 mL) at 130 oC for 24 h under air
.
N
N
N
N
N
N
N
N
N
b Isolated yields.
c 18 h.
Cl
CF3
Cl
F3
C
F3
C
CF3
3dl, 54%
3cl, 65%
3cg, 78%
aReaction conditions: 1 (1.0 equiv, 0.5 mmol), 2 (1.0 equiv), KOH (3.0
o
d 36 h.
equiv), sulfur powder (0.75 equiv) and DMSO (2.0 mL) at 130 C for 24 h
under air. All reported yields are isolated yields.
45% yield (entry 1). To our delight, increasing the amount of
sulfur powder could promote the formation of product 3aa
(3ad,3ai) and Br (3aj) were tested and provided 1,3,5-triazines in
moderate to good yields. However,
a trace amount of

3
corresponding product was obtained with a methoxy group on
the phenyl ring of benzyl chloride at the para- position. Also,
electron-donating groups at the meta- position on the phenyl
ring of benzyl chloride afforded higher yield of the
corresponding products than that at para- position (3ag vs
3ab, 3ah vs 3ac). This suggested the position of the
substituents affected the reaction. As aromatic substrate, 2-
(chloromethyl) naphthalene gave the corresponding product
3am in 42% yield. The reaction of para-chlorobenzamidine,
para-bromobenzamidine, para-trifluoromethyl benzamidine
with various arylmethyl chlorides also processed smoothly
to provided 1,3,5-triazines (3ba-3dl) in moderate to good
yields (54%-78%).
We next developed a general protocol for 1,2,4-thiadiazoles
formation, which was isolated as a side product in our initial
studies (Table 3). Using Na2CO3 as the base, the increased yields
of 1,2,4-thiadiazole 4aa were observed with increasing amount of
sulfur powder (entries 1-9), and we chose 5.0 equiv elemental
sulfur as the best choice (entry 8). The effect of various bases on
the product 4aa yield was investigated, which indicated that
Na2CO3 is the best choice (entry 8 vs. entries 10-14). Then
majorization focused on the solvent, which referred that DMSO
is the best choice (entry 8 vs entries 15-16). An increase in 60%
yield of 4aa occurred when using 2.0 equiv of benzamidine
hydrochloride 1a, 1.0 equiv of benzyl chloride 2a and 4.0 equiv
Na2CO3 (entry 17). Also, lowering the reaction temperature to
120 °C was not detrimental for the 1,2,4-thiadiazole formation
(entry 18 vs entry 17). However, decreasing the reaction
temperature further to 110 °C resulted in a lower yield of 4aa
(entry 19 vs entry 18). Thus, the best reaction conditions for
1,2,4-thiadiazole 4aa were: benzamidine hydrochloride 1a (2.0
equiv, 1.0 mmol), benzyl chloride 2a (1.0 equiv), sulfur powder
(5.0 equiv), Na2CO3 (4.0 equiv) and DMSO (2.0 mL) at 120 °C
for 24 h (entry 14).
In the process of our exploring the synthesis of 1,3,5-triazines,
in an accidental opportunity, by changing the stoichiometry of
sulfur powder, a novel method for 1,2,4-thiadiazoles synthesis
was established. 1,2,4-Thiadiazoles which have an
unsymmetrical five-membered rings display a wide range of
applications in medicinal chemistry.13 For example, Cefozopran14
is a commercial drug used to against several bacterial infections,
which contains a 3,5-disubstituted 1,2,4-thiadiazole scaffold
(Figure 1). In addition, 1,2,4-thiadiazoles are useful as thiol
trapping agents, pesticides, and corrosion inhibitors.15 Cheng and
co-workers reported a method for the synthesis of 1,2,4-
Furthermore, we explored the substrate scopes for the 1,2,4-
thiadiazoles and the results were summarized in Table 4. As we
can see, benzamidine hydrochloride was used to couple with 1-
thiadiazoles
from
arylmethyl
bromides,
arylamidine
(chloromethyl)-4-methylbenzene
and
1-(chloromethyl)-3-
hydrochlorides and elemental sulfur under nitrogen atmosphere
methylbenzene, providing 3-Phenyl-5-(p-tolyl)-1,2,4-thiadiazole
4ab in 60% yield and 3-Phenyl-5-(m-tolyl)-1,2,4-thiadiazole 4ag
in 57% yield. Besides, benzamidine hydrochloride with halogen
substituent such as Cl proceeded smoothly to form corresponding
product 4da in 42 % yield. When benzyl chloride with a phenyl
group, 50% yield was obtained (4ao). As aromatic heterocyclic
substrate, 2-(chloromethyl)pyridine offered the corresponding
product 4an in 64% yield. Moreover, the reaction of para-
trifluoromethyl benzamidine with benzyl chloride gave the
desired product 4ca in 75% yield. Then, the reaction of p-
methylbenzidine hydrochloride with benzyl chloride gave the
product 4ea in 51% yield.
in 2017.16
Table 3 The selectivity variation of the cyclization reactions
and the optimization of 1,2,4-thiadiazole synthesisa
NH·HCl
S
N
Cl
S8
NH2
N
N
N
conditions
N
1a
2a
4aa
3aa
Entry
S8
(equiv)
Base
Tem
p
(oC)
Solvent
Yieldb (%)
3aa
4aa
Table 4 Substrate scopes for 1,2,4-thiadiazoles synthesisa
N
NH·HCl
S
R1
Cl
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17c
18c
0.25
0.5
0.75
1
2
3
4
5
6
5
5
5
5
5
5
5
5
5
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
K3PO4
130
130
130
130
130
130
130
130
130
130
130
130
130
130
130
130
130
120
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
Toluene
THF
45
50
68
61
50
31
21
21
20
19
12
9
18
20
25
13
14
15
trace
trace
trace
19
21
23
34
50
51
41
28
9
50
40
trace
25
60
NH2
N
R2
Na2CO3
S8
R1
DMSO
R2
120 oC, 24 h
4
2a, d, g,n, o
1a, c
N
N
N
N
N
S
S
S
N
4ag, 57%
4aa, 60%
4ab, 60%
N
S
N
N
N
S
N
4an, 64%
4ao, 50%
t-BuOK
KOH
K2CO3
N
S
N
N
N
S
S
Cl
CF3
N
N
NaOH
4ca, 75%
4da, 42%
4ea, 51%
Na2CO3
Na2CO3
Na2CO3
Na2CO
aReaction conditions: 1 (2.0 equiv, 1 mmol), 2 (1.0 equiv), Na2CO3 (4.0
equiv), sulfur powder (5.0 equiv) and DMSO (2.0 mL) at 120 oC for 24 h
under air. All reported yields are isolated yields.
DMSO
DMSO
60
To probe the mechanism of the reaction, the control
experiments were performed (Scheme 2). When the reaction for
the synthesis of 1,3,5-triazines took place under an atmosphere of
nitrogen, an obviously decreased reactivity was observed
(Scheme 2, eq 1). Thus, molecular O2 might involve the reaction
process for the synthesis of 1,3,5-triazines. And molecular O2
was not important factor for 1,2,4-thiadiazole formation (Scheme
2, eq 2). On the other hand, a free radical control experiment was
3
19c
5
Na2CO3
110
DMSO
18
44
aReaction conditions: 1a (1.0 equiv, 0.5 mml), 2a (1.0 equiv), sulfur powder,
base (3.0 equiv), and DMSO (2.0 mL) at 130 oC for 24 h under air.
bIsolated yields.
c1a (2.0 equiv, 1 mmol), Na2CO3 (4.0 equiv) .

4
Tetrahedron Letters
Conclusion
designed ,addition of 2.0 equivalents free radical scavengers ,
such as 2,2,6,6-tetramethylpiperidine oxynitride (TEMPO) or
2,6-di-tert-butyl-4 Methylphenol (BHT), there was no
In summary, we have reported a novel metal-free approach to
-
the synthesis of 1,3,5-triazine derivatives in moderate to good
yields by using elemental sulfur to promote the cyclization of
benzyl chlorides and amidines. By changing the stoichiometry of
benzyl chlorides, amidines, elemental sulfur and base, an
effectively alternative approach to access 1,2,4-thiadiazoles has
also been developed (Scheme 4). Detailed mechanistic studies
and extension to other heteroaromatic substrates of this protocol
are under way in our laboratory.
significant decrease in the yield of 1,3,5-triazine product 3aa or
1,2,4-thiadiazole 4aa, which confirmed that the reaction process
does not include free radical step (Scheme 2, eq 3 and eq 4 ).
NH·HCl
NH2
S
N
1
S
8(0.75eq), KOH, DMSO
2, 130 oC, 24 h
Cl
N
+
N
N
+
N
N
1a
2a
4aa
, trace
3aa
, 42%
NH·HCl
NH2
S
N
N
2
S
8(5eq), Na2CO3, DMSO
2, 120 oC, 24 h
NH·HCl
NH2
Cl
+
N
N
+
S
S
8 (0.75 equiv)
N
Cl
S
8 (5.0 equiv)
N
N
N
+
N
N
KOH, DMSO
Na2CO3, DMSO
N
4aa
, 53%
2a
1a
3aa
, 13%
60%
82%
NH·HCl
NH2
S
8(0.75eq), KOH, DMSO
Cl
+
N
N
3
N
2, 130 oC, 24 h
Scheme 4 The synthesis of 1,3,5-triazine and 1,2,4-
N
1a
2a
3aa
thiadiazole.
TEMPO (2 equiv)
BHT (2 equiv)
78%
80%
Acknowledgments
NH·HCl
NH2
S
N
4
S
8(5eq), Na2CO3, DMSO
2, 120 oC, 24 h
Cl
N
We thank Major National Science and Technology Program of
China for Innovation Drug (2017ZX09101002-001-004), the Six
Talent Peaks Project in Jiangsu Province (No. 2015-SWYY-016)
and Postgraduate Research & Practice Innovation Program of
Jiangsu Province (Grant No. SJCX17_0287) for supporting this
research.
+
N
N
+
N
N
2a
1a
4aa
3aa
14%
15%
58%
59%
TEMPO (2 equiv)
BHT (2 equiv)
Scheme 2. Control experiments.
Based on the above findings, a plausible mechanism is
proposed (Scheme 3).11,
Initially, the amidine 1a’ is
16, 17
References and notes
neutralized by base from its hydrochloride salt. 1a’ and benzyl
chloride form intermediate 5 which undergoes an elimination
reaction to give intermediate 6. The subsequent nucleophilic
addition of the amino group to the electrophilic carbon center
would afford intermediate 7 and racemic aminals 8. Finally, the
thermodynamically favourable deamination may release
ammonia and dihydrotriazine 9, followed by dehydrogenative
aromatization to afford the product 3aa. On the other hand, the
intermediate 5 undergoes an isomerization reaction and reacts
with elemental sulfur, generating intermediate 10. Then,
intermediate 10 undergoes imine isomerization reaction to give
intermediate 11, and 4H-thiadiazole 12 is obtained via
intramolecular cyclization of 11 with a new C-S bond formed.
Finally, dehydrogenation of 12 forms the desired product 4aa.
1
2
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4858.
3
4
NH
H
2N
Ph
Ph
Ph
N
N
Ph
NH
NH
NH2
Ph
N
N
NH
Ph
NH
H
Ph
NH2
6
Ph
8
7
H2S
O2/Sn
NH
Cl
NH3
HN
Ph
Ph
5
6
NH2
Ph
NH
NH
5
1a'
N
Ph
N
Ph
Sn
-H
KOH
9
N
Ph
NH·HCl
NH2
O2/Sn
H2S
Ph
NH
Sn
Ph
N
N
N
10
1a
Ph
Ph
3aa
7
8
Biswas, S.; Batra, S. Eur. J. Org. Chem. 2012, 2012, 3492.
Xie, F.; Chen, M.; Wang, X.; Jiang, H.; Zhang, M. Org. Biomol.
Chem. 2014, 12, 2761.
You, Q.; Wang, F.; Wu, C.; Shi, T.; Min, D.; Chen, H.; Zhang, W.
Org. Biomol. Chem. 2015, 13, 6723.
2 S2- + 4 H+
Ph
S
N
Ph
2 S
Ph
-Sn-1
H+
HN
N
Ph
NH
S
N
Ph
Ph
N
H
9
Sn
4aa
11
12
Scheme 3. Plausible Mechanism.
10 Tiwari, A. R.; Akash, T.; Bhanage, B. M. Org. Biomol. Chem. 2015,
13, 10973.
11 Tiwari, A. R.; Bhanage, B. M. Green Chem. 2016, 18, 144.

5
12 Wang, X.; Miao, D.; Li, X.; Hu, R.; Yang, Z.; Gu, R.; Han, S.
Tetrahedron 2017, 73, 5194.
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Supplementary Material
Supplementary material that may be helpful in the review
process should be prepared and provided as a separate electronic
file. That file can then be transformed into PDF format and
submitted along with the manuscript and graphic files to the
appropriate editorial office.
14 Iizawa, Y.; Okonogi, K.; Hayashi, R.; Iwahi, T.; Yamazaki, T.; Imada,
A. Antimicrob. Agents Chemother. 1993, 37, 100.
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16 Zhou, Z.; Liu, M.; Sun, S.; Yao, E.; Liu, S.; Wu, Z.; Yu, J.; Jiang, Y.;
Cheng, J. Tetrahedron Lett. 2017, 58, 2571.

6
Tetrahedron Letters
1.1,3,5-Triazines or 1,2,4-thiadiazoles can be
alternatively prepared.
2.An selectively metal-free synthesis mediated by
elemental sulfur.
3.The yield was moderate to good.
4.Good functional group tolerance.