Transition-metal-free S-N bond formation: Synthesis of 5-amino-1,2,4-thiadiazoles from isothiocyanates and amidines

Article abstract of DOI:10.1039/c9nj01419e

A novel and green method for the synthesis of 5-amino-1,2,4-thiadiazoles has been developed by the reaction of isothiocyanates with amidines. This protocol which is free of metal, catalyst and iodine involves O₂ oxidative S-N bond formation for

Full text of DOI:10.1039/c9nj01419e

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Jason B. Benedict et al.
The role of atropisomers on the photo-reactivity and fatigue of
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DOI: 10.1039/C9NJ01419E
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Transition-Metal-Free S-N Bond Formation: Synthesis of 5‑Amino-
1,2,4-Thiadiazoles form Isothiocyanates with Amidines
Zan Yang, Ting Cao, Si Liu, An Li, Kun Liu, Tao Yang*, and Congshan Zhou*
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
A novel and green method for the synthesis of 5‑amino-1,2,4- thiadiazoles have been developed.11 Nakka and co-works
thiadiazoles has been developed by reaction of isothiocyanates reported an efficient method for the construction of S-N bond
with amidines. This protocol which is free of metal, catalyst and from imidoyl thioureas with benzonitriles by employing PIDA as
iodine involves O2 oxidative S-N bond formation for the synthesis catalyst for the synthesis of 5-imino-1,2,4-thiadiazoles.12
A
of various 5‑amino- 1,2,4-thiadiazole derivatives with excellent to novel method for the synthesis of 5‑amino-1,2,4-thiadiazoles
good yields. High regioselectivity, mild reaction conditions, broad from 2-aminopyridine/amidine with isothiocyanate has been
substrate scope and good functional group tolerance are the developed by copper catalyzed S-N bond formation.13 However,
highlights of the report.
the required metal catalyst, strong oxidative reaction
conditions and harsh reaction conditions can limit the
application of this reaction. Herein, we developed a metal and
iodine free direct construction of S-N bond from amidines with
isothiocyanates for the synthesis of 5-amino-1,2,4-thiadiazoles.
Previous works
The development of efficient and convenient approach for the
construction of S-X (X = C, N, S, P) bonds has attracted much
attention owing to the ubiquitous existence of organosulfur
compounds.1 For instance, the S-N bond containing compounds
are the key structural motif of many natural products, medicinal
materials, biologically and organic functional materials.2
Nevertheless, the traditional S-N bond formation depends on
the reactions of transition-metal-catalyzed aerobic oxidation or
oxidative coupling using oxidants.3 However, most of these
approaches suffer from the usage of expensive reagents, metal
catalysts, harsh and strong oxidative reaction conditions.
Therefore, the development of a novel and green method for
the construction of S-N bond is still highly desirable.
N
N
S
Oxidative dimerization
ref 10
S
R
R
NH2
NH
R1
R
N
N
S
S
[M] or I2 or PIDA
ref 11
R
R
R
N
N
N
H
H
H
This work
N
S
NH
TMEDA
N
1,2,4-Thiadiazoles are an important class of sulfur-containing
R2
+
C
R2
R1
N
S
MeCN, 90 oC, Air
N
heterocycles because of their wide applications in the R1
pharmaceutical areas. These sulfur-containing heterocycles
have a broad of biological activities such as antimicrobial4,
antirheumatic5, anti-inflammatory antibiotic6, antiulcerative7,
antibacterial8, antidiabetic9. The general approaches for the
synthesis of 1,2,4-thiadiazoles involve oxidative cyclization of
thiourea or thioamides with various oxidants.10 Recently, I2 or
PIFA -catalyzed intramolecular oxidative S-N bond formation of
imidoyl thioureas for the synthesis of 5-amino-1,2,4-
NH2 HCl
H
27 examples, up to 96% yield
Metal-free
Air as the only oxidant
Broad substrate scope
Gram-scale synthesis
Scheme 1. Various method for the synthesis of 1,2,4-
thiadiazoles
At first, benzamidine hydrochloride (1a) and 4-methylphenyl
isothiocyanate (2a) were chosen as model substrates to
optimize the S-N bond formation reaction conditions. As shown
in Table 1, when 10 mol% I2 was used as a catalyst with 0.5 mmol
NEt3 as a base, in MeCN at 80 oC under air atmosphere for 16 h,
the reaction of 1a with 2a gives the 5-amino-1,2,4-thiadiazole
3a in 54% yield (Table 1, entry 1). To our surprise, in the absence
of a catalyst I2, the desired product 3a was observed in 67% yield
a. College of Chemistry and Chemical Engineering, Hunan Institute of Science and
Technology, Yueyang 414006, P. R. China. E-mail: zhoucongsh@126.com,
yangtaozcs@126.com
† Footnotes relating to the title and/or authors should appear here.
Electronic Supplementary Information (ESI) available: [details of any supplementary
information available should be included here]. See DOI: 10.1039/x0xx00000x
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(Table 1, entry 2). Therefore, the different bases such as, DIPEA amidines were compatible with the optimized conditions as
View Article Online
DOI: 10.1039/C9NJ01419E
(N,N-diisopropylethylamine),
pyridine,
DABCO
(1,4- well, affording the desired 5‑amino-1,2,4-thiadiazoles 3ja and
diazabicyclo[2.2.2]octane), DBU (1,8-diazabicyclo[5.4.0]undec- 3ka in good yields. However, 2-aminopyridine (1l) failed to
7-ene), TMEDA (N,N,N',N'-tetramethylethylenediamine), afford the corresponding product 3la under the optimized
K2CO3, K3PO4, Na2CO3, NaOAc were also investigated, and DIPEA conditions.
exhibited good activity with an isolated yield up to 92% (Table
1, entries 3-11). Moreover, when the amount of base was Scheme 2. Substrate Scope of Amidinesa
N
N
NH
S
decreased from 2.0 eq to 1.0 eq, the yield of product 3a
decreased to 37%, and increasing the amount of base to 3.0 eq
did not increase of the product yield (Table 1, entries 12-13).
Further, the effect of solvents, i.e., MeCN, DMSO, DMF, DMA,
THF and Dioxane was studied, and MeCN is the best solvent for
this transformation (Table 1, entries 14-18). Next, changed the
reaction temperature did not lead to any further improvements
in the yield, 80 oC gave the best result (Table 1, entries 19-20).
TMEDA
10
11
12
13
14
15
16
17
18
19
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C
+
R
S
80 oC, MeCN, 16 h
N
R
NH2 HCl
N
H
1
2a
3
S
N
S
N
S
N
N
N
N
N
N
H
H
N
H
MeO
3ca, 87%
3ba, 89%
3aa, 92%(85%b)
Table 1. Optimization of reaction conditionsa
NH
N
S
N
S
S
N
N
S
N
C
+
N
N
NH2 HCl
S
N
N
H
N
N
H
N
N
H
Cl
H
Br
F
3ea, 75%
1a
2a
3aa
3fa, 72%
3da, 80%
Entry
1
2
3
4
5
6
7
8
Catalyst
Base
Et3N
Et3N
Solvent
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
DMSO
DMF
Yield [%]b
54
S
S
N
N
S
N
N
N
N
N
I2
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
N
N
H
H
N
N
H
N
67
85
47
52
Trace
92
43
Trace
27
Trace
84
37
75
82
60
57
56
65
72
N
3ia, 84%
3ga, 85%
3ha, 78%
DIPEA
N
pyridine
DABCO
DBU
TMEDA
K2CO3
S
N
S
N
S
N
N
N
N
N
H
N
H
3la, N. R.
3ka, 87%
3ja, 88%
aReaction conditions: 1 (0.25 mmol), 2a (0.25 mmol), TMEDA (0.5
mmol), in MeCN (2 mL), under air atmosphere, at 80 oC for 16h.
bThe yield of gram-scale synthesis (5 mmol).
9
K3PO4
10
11
12c
13d
14
15
16
17
18
19e
20f
Na2CO3
NaOAc
TMEDA
TMEDA
TMEDA
TMEDA
TMEDA
TMEDA
TMEDA
TMEDA
TMEDA
To further explore the substrate scope of this S-N bond forming
reaction, various isothiocyanates were investigated under the
optimized conditions. As shown in Scheme 3, aryl
isothiocyanates with electron-donating groups (methyl 3ac, 3ad
and 3ag, isopropyl 3ae, butyl 3af, methoxy 3ah, and ethoxy 3ai)
resulted in higher reactivity than those with electron-
withdrawing groups (fluoro 3aj, and chloro 3ak and 3al), and
produced the respective products in moderate to excellent
yields. Besides, the positions of the substituents in aromatic
rings greatly affected the reaction yield. In addition, the 1-
isothiocyanatonaphthalene (2m) was also tolerated under the
optimized condition, and the desired product 3am was afforded
in 83% yield. To our delight, benzyl and alkyl isothiocyanates
reacted with benzamidine hydrochloride smoothly to give the
corresponding products 3an, 3ao and 3ap in 82%, 86% and 81%
yield, respectively.
DMA
THF
Dioxane
MeCN
MeCN
aReaction conditions: 1a (0.25 mmol), 2a (0.25 mmol), catalyst
(10 mol%), base (0.5 mmol), in solvent (2 mL), under air
atmosphere, at 80 oC for 16h. bIsolated yields. cBase (0.6 mmol).
dBase (0.3 mmol). eAt 60 oC. f At 100 oC.
Under the optimized conditions, we investigated the substrate
scope of other amidines 1 in this oxidative S-N bond forming
reaction. As shown in Scheme 2, both electron-withdrawing and
electron-donating arylamidines reacted with 4-methylphenyl
isothiocyanate (2a) to afford the desired 5‑amino-1,2,4-
thiadiazoles 3ca-3fa in moderate to excellent yields. Various
functional groups, including p-Me, p-OMe, and halogenated (p-
F, Cl, Br) were tolerated. Moreover, heterocycle substituted
amidines, such as 4- and 3-pyridyl, 1H-pyrazolyl, were reacted
with 2a, and the expected products of 3ga, 3ha and 3ia in 85%,
78% and 84% yields, respectively. It is notable that alkyl
Scheme 3. Substrate Scope of Isothiocyanatesa
NH
N
S
TMEDA
N
+
C
R1
R1
NH2 HCl
N
S
N
80 oC, MeCN, 16h
H
1a
2
3
2 | J. Name., 2012, 00, 1-3
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from the intermediate A in the presence of TVMiewEDArAtic.leTOhnleinne
intermediate A is oxidized by O2 to giDvOeI:t1h0e.10s3u9l/fCu9rNJr0a1d4i1c9aEl
intermediate B.14c Meanwhile, the intermediate C was formed
by an intramolecular radical-cascade cyclization of B, then C
undergoes deprotonation under the presence of TMEDA or O2
to provide the final product 3aa.
S
S
S
N
N
N
N
N
N
N
H
N
H
N
H
3ac, 85%
3ab, 81%
3ad, 80%
S
N
S
N
S
N
N
Scheme 5. Proposed Reaction Mechanism
N
N
10
11
12
13
14
15
16
17
18
19
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60
H
N
N
H
N
H
N
C
S
3ag, 88%
NH
S
3ae, 91%
3af, 96%
NH
NH2 HCl
F
OEt
OMe
2a
N
N
H
S
N
S
N
TMEDA
S
N
A
N
N
N
N
H
N
H
N
H
1a
-
-
NH
S
O2
O2
S
3aj, 84%
HN
3ai, 85%
3ah, 81%
NH
NH
N
N
Cl
H
N
Cl
S
N
S
N
C
S
N
B
N
N
N
H
N
N
H
N
H
O2
O2
-H+
3al, 68%
S
S
3am, 83%
3ak, 78%
HN
N
NH
S
N
N
N
S
S
N
N
NH
NH
N
N
N
D
3aa
N
H
3ao, 86%
3an, 82%
3ap, 81%
aReaction conditions: 1a (0.25 mmol), 2 (0.25 mmol), TMEDA (0.5
Conclusions
mmol), in MeCN (2 mL), under air atmosphere, at 80 oC for 16h.
In summary, we have developed a novel and green method for
the construction of S-N bond from isothiocyanates with
amidines, producing a variety of aryl 5‑amino-1,2,4-thiadiazoles
in moderate to excellent yields. This transition-metal-free
methodology features a wide functional group tolerance with
inexpensive and commercially available material, and no
addition extra catalyst or oxidant. Meanwhile, the detailed
mechanistic study and further applications of this green
reaction for S-N bond formation are currently undergoing in our
laboratory.
In order to better understand the mechanism of the S-N bond
forming reaction, a series of control experiments were carried
out in Scheme 4. Firstly, 1.0 eq. of the radical scavenger TEMPO
(2,2,6,6-tetramethyl-1-piperidinyloxy) and BHT (2,6-di-tert-
butyl-4-methylphenol) was added into the reaction under
standard conditions, the product of 3aa was obtained in 90%
and 87% yield, respectively (Scheme 4, eq. 1). In additon, when
we changed the same reaction under N2 atmosphere, no
desired product was observed (Scheme 4, eq. 2). To our
surprise, 1.0 eq. of the radical scavenger TEMPO was added into
the reaction under N2 atmosphere, generating the
corresponding products 3aa in 41% yield (Scheme 4, eq. 2).
These control experimental results suggested that a single
electron transfer (SET) process may be involved in the O2
mediated radical-cascade cyclization reaction.
This work was supported by National Natural Science
Foundation of China (No. 21476068), Natural Science
Foundation of Hunan Province (No. 2019JJ50214).
Conflicts of interest
There are no conflicts to declare.
Scheme 4. Control Experiments
Notes and references
NH
NH2 HCl
N
S
N
standard conditions
radical scavenger
C
(1)
+
S
1
(a) K. L. Dunbar, D. H. Scharf, A. Litomska, C. Hertweck,
Chem. Rev., 2017, 117, 5521; (b) V. Bizet, C. M. M. Hendriks,
C. Bolm, Chem. Soc. Rev., 2015, 44, 3378; (c) P. Majumdar, A.
Pati, M. Patra, R. K. Behera, A. K. Behera, Chem. Rev., 2014,
114, 2942; (d) T. S. Kumar, T. Yang, S. Mishra, C. Cronin, S.
Chakraborty, J. Shen, B. T. Liang, K. A. Jacobson, J. Med.
Chem., 2013, 56, 902; (e) N. Li, J. K. Frederiksen, J. A. Piccirilli,
Acc. Chem. Res., 2011, 44, 1257; (f) Z. Yang, Y. Yan, A. Li, J.
Liao, L. Zhang, T. Yang, C. Zhou, New. J. Chem., 2018, 42,
14738; (g) Z. Yang, J. Li, J. Hua, T. Yang, J. Yi, C. Zhou, Synlett
2017, 28, 2325; (h) C. Balakrishna, R. Gudipati, V. Kandula, S.
Yennam, P. U. Devi, M. Behera, New J. Chem., 2019, 43,
2458.
N
N
H
1a
2a
3aa
radical scavenger:
TEMPO
BHT
Yield: 90% (1.0 eq) 87% (1.0 eq)
NH
NH2 HCl
N
S
N
standard conditions
C
(2)
+
S
N
N
TEMPO (X eq)
N2
H
1a
2a
3aa
N. R. (X = 0)
42% (X = 1)
Inspired by the above analysis and literature reports14, a
plausible mechanism was proposed in Scheme 5. Firstly,
benzamidine hydrochloride 1a react with isothiocyanate 2a to
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(a) F. Viani B. Rossi, W. Panzeri, L. Merlini, A. M. Martorana,
A. Polissi, Y. M. Galante, Tetrahedron 2017, 73, 1745; (b) M.
A. Abdelgawada, M. B. Labib, W. A. M. Ali, G. Kamel, A. A.
Azouz, E. EL-Nahass, Bioorg. Chem., 2018, 78, 103; (c) C.
Gnamm, A. Jeanguenat, A. C. Dutton, C. Grimm, D. P. Kloer,
A. J. Crossthwaite, Bioorg. Med. Chem. Lett., 2012, 22, 3800;
(d) J. Gising, A. K. Belfrage, H. Alogheli, A. Ehrenberg, E.
Åkerblom, R. Svensson, P. Artursson, A. Karlén, U. H.
Danielson, M. Larhed, A. Sandström, J. Med. Chem., 2014,
57, 1790; (e) B. A. Shainyan, L. L. Tolstikova, Chem. Rev.,
2013, 113, 699; (f) S. Sivaramakrishnan, K. Keerthi, K. S.
Gates, J. Am. Chem. Soc., 2005, 127, 10830.
ike, N. Kambe, J. Org. Chem., 2007, 72, 8087; (c)VHiew. LAirutic,leY.Online
Fang, S. Wang, S. Ji, Org. Lett., 2018, 20, 930.
DOI: 10.1039/C9NJ01419E
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
3
(a) O. M. Mulina, A. I. llovaisky, A. O. Terent'ev, Eur. J. Org.
Chem., 2018, 2018, 4648; (b) K. Hofman, N. Liu, G.
Manolikakes, Chem. Eur. J., 2018, 24, 11852; (c) Z. Wang, Y.
Kuninobu, M. Kanai, J. Org. Chem., 2013, 78, 7337; (d) C. Lee,
X. Wang, H. Jang, Org. Lett., 2015, 17, 1130; (e) A. Correa, I.
Tellitu, E. Domínguez, R. SanMartin, Org. Lett., 2006, 8, 4811;
(f) E. Rattanangkool, W. Krailat, T. Vilaivan, P.
Phuwapraisirisan, M. Sukwattanasinitt, S. Wacharasindhu,
Eur. J. Org. Chem., 2014, 2014, 4795; (g) S. Yotphan, L.
Sumunnee, D. Beukeaw, C. Buathongjan, V. Reutrakul, Org.
Biomol. Chem., 2016, 14, 590; (h) X. Pan, J. Gao, J. Liu, J. Lai,
H. Jiang, G. Yuan, Green Chem., 2015, 17, 1400; (i) T. Yu, Y.
Hou, Y. Jiang, W. Xu, T. Shi, X. Wu, J. Zhang, D. He, Z. Wang,
Tetrahedron Lett., 2017, 58, 2084.
(a) A. M. Farag, A. S. Mayhoub, S. E. Barakat, As. H. Bayomi,
Bioorg. Med. Chem., 2008, 16, 4569; (b) S. Bondock, W.
Fadaly, M. A. Metwally, Eur. J. Med. Chem., 2009, 44, 4813;
(c) W. Huang, G. Yang, Bioorg. Med. Chem., 2006, 14, 8280.
J. K. Chakrabarti, C. V. Smith, W. R. N. Williamson, E.P. Patent
EP19910455356 A1, 1991.
P. C. Unangst, G. P. Shrum, D. T. Connor, R. D. Dyer, D. J.
Schrier, J. Med. Chem., 1992, 35, 3691.
K. Kharimian, T. F. Tam, R. C. S. H. Leung-Toung, W. Li, PCT
Int. Appl. WO1999051584A1, 1999.
(a) T. Yamanaka, H. Ohki, M. Ohgaki, S. Okuda, A. Toda, K.
Kohji, S. Inoue, K. Misumi, K. Itoh, K. Satoh, U.S. Patent US
2005004094A1, 2005; (b) I. R. Ager, A. C. Barnes, G. W.
Danswan, P. W. Hairsine, D. P. Kay, P. D. Kennewell, S. S.
Matharu, P. Miller, P. Robson, D. A. Rowlands, W. R. Tully, R.
Westwood, J. Med. Chem., 1988, 31, 1098.
(a) C. Johnstone, D. Mckerrecher, K. G. Pike, M. J. Waring,
PCT Int. Appl. WO2005121110A1, 2005; (b) L. D. Nunno, C.
Franchini, A. Scilimati, M. S. Sinicropi, P. Tortorella,
Tetrahedron: Asymmetry 2000, 11, 1571.
4
5
6
7
8
9
10 (a) A. S. Mayhoub, E. Kiselev, M. Cushman, Tetrahedron Lett.,
2011, 52, 4941; (b) I. A. Ryu, J. Y. Park, H. C. Han, Y. Gong,
Synlett 2009, 999; (c) J. R. Cashman, R. P. Hanzlik, J. Org.
Chem., 1982, 47, 4645; (d) D. Yaşar, Y. Muhammet, A. Asli, J.
Chem. Res., 2008, 2008, 235; (e) H. Kim, S. H. Kwak, G. Lee, Y.
Gong, Tetrahedron 2014, 70, 8737; (f) N. Tumula, N. Jatangi,
R. K. Palakodety, S. Balasubramanian, M. Nakka, J. Org.
Chem., 2017, 82, 5310.
11 (a) B. Wang, Y. Meng, Y. Zhou, L. Ren, J. Wu, W. Yu, J. Chang,
J. Org. Chem., 2017, 82, 5898; (b) A. Mariappan, K. Rajaguru,
N. M. Chola, S. Muthusubramanian, N. Bhuvanesh, J. Org.
Chem., 2016, 81, 6573; (c) N. Tumula, N. Jatangi, K. P. Radha,
S. Balasubramanian, M. Nakka, J. Org. Chem., 2017, 82, 5310;
(d) N. Jatangi, N. Tumula, K. P. Radha, M. Nakka, J. Org.
Chem., 2018, 83, 5715.
12 N. Tumula, R. K. Palakodety, S. Balasubramanian, M. Nakka,
Adv. Synth. Catal., 2018, 360, 2806.
13 W. Yu; Y. Huang, J. Li, X. Tang, W. Wu, H. Jiang, J. Org. Chem.,
2018, 83, 9334.
14 (a) Y. Asanuma, S. Fujiwara, T. Shin-ike, N. Kambe, J. Org.
Chem., 2004, 69, 4845; (b) S. Fujiwara, Y. Asanuma, T. Shin-
4 | J. Name., 2012, 00, 1-3
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