Electronic Supplementary Information

One-pot Synthesis of 3,5-Disubstituted 1,2,4-Thiadiazoles from

Nitriles and Thioamides via I2-Mediated Oxidative Formation of N-S

Bond

Ling Chai,a,‡ Yuanqing Xu,a,‡ Tao Ding,a,‡ Xiaomin Fang,a Yanpeng Wang,a Wenkai Zhang,a Minghua Lu,a Hao Xu,*,a Xiaobo Yang*,b

a College of Chemistry and Chemical Engineering, Henan University, Kaifeng 475004, P. R.

China.

b College of Chemistry & Chemical Engineering, Shenyang Normal University, Shenyang,

Liaoning, 110034, P. R. China.

E-mail : xuhao@henu.edu.cn; bxy1223@gmail.com

Table of contents

General experimental procedures P2

Scheme S1 P3

Figure S1 P4

Figure S2 P6

Reference P7

The 1H and 13C NMR spectra of compounds 3a-3b’, III-1, 4a P8

S1

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry.This journal is © The Royal Society of Chemistry 2017

General experimental procedures

All reactions were carried out under air. Proton and carbon magnetic resonance

spectra (1H NMR and 13C NMR) were recorded using tetramethylsilane (TMS) in the

solvent of CDCl3 as the internal standard (1H NMR: TMS at 0.00 ppm,CHCl3 at 7.26

ppm; 13C NMR: CDCl3 at 77.16 ppm) or were recorded using tetramethylsilane (TMS)

in the solvent of d6-DMSO as the internal standard (1H NMR: TMS at 0.00 ppm,

DMSO at 2.50 ppm; 13C NMR: DMSO at 39.51 ppm).

Compounds 2b-j was synthesized by previous method.[1]

S2

Alk2

SN

NAlk1S

Alk2H2NAlk1 CN +

1

standard conditons

Alk1 = methyl, ethyl, benzyl; Alk2 = methyl, ethyl

(D)

Ph

SN

NPhS

PhH2N+

2a 4a

standard conditons(E)

Ar = 4-CH3Ph, 4-ClPh

+ Ar

SN

NAr Ph

SN

NArAr CN +

Ph

SN

NRS

PhH2NR CN +

standard conditons(B)

R=4-NH2Ph, 4-N(CH3)2Ph, N

SN

NBn

S

H2N+

standard conditonsCN(A)O

CH3CH3

O

1g

2a

(C) t-BuCNS

PhH2N2a

+Ph

SN

Nt-Bustandard conditons

Scheme S1. (A) Employing 4-acetylbenzothioamide as the substrate to react with 1g; (B) Employing amino-substituted nitriles as the substrates to react with 2a; (C) Employing pivalonitrile as the substrate to react with 2a; (D) Employing aliphatic thioamides as the substrates to react with aliphatic nitriles 1 under standard conditions; (E) Employing aromatic nitriles as substrates to react with 2a.

S3

Figure S1. ESI-MS [M+H]+ spectrum of reaction solution of p-methylbenzonitrile with

thiobenzamide 2a.a [aReaction condition: (1) 1 (0.8 mmol), 2 [0.4 mmol, added (4×0.1 mmol per 5

min)], AlCl3 (0.8 mmol), n-BuAc (1 mL), reaction time (5 h) at 70 oC in air; (2) then H2O (0.3

mL), I2 (0.8 mmol), reaction time (24 h) at room temperature. The resulting solution was

S4

Ph

SN

NPh

4a

Ph

SN

NH3C

SN

NH3C CH3

quenched with saturated aqueous solution of Na2S2O3. The organic and aqueous layers were

separated, and the aqueous layer was extracted with EtOAc (3×10 mL). The combined organic

layers were dried over anhydrous Na2SO4, concentrated and purified by column chromatography

on silica gel, and the crude product is used to do the ESI-MS test. ]

S5

Figure S2. ESI-MS [M+H]+ spectrum of reaction solution of p-chlorobenzonitrile with

thiobenzamide 2a.a [aReaction condition: (1) 1 (0.8 mmol), 2 [0.4 mmol, added (4×0.1 mmol per 5

min)], AlCl3 (0.8 mmol), n-BuAc (1 mL), reaction time (5 h) at 70 oC in air; (2) then H2O (0.3

mL), I2 (0.8 mmol), reaction time (24 h) at room temperature. The resulting solution was

S6

Ph

SN

NPh

4aPh

SN

NCl

SN

NCl Cl

quenched with saturated aqueous solution of Na2S2O3. The organic and aqueous layers were

separated, and the aqueous layer was extracted with EtOAc (3×10 mL). The combined organic

layers were dried over anhydrous Na2SO4, concentrated and purified by column chromatography

on silica gel, and the crude product is used to do the ESI-MS test.]

References

(1) Goswami, S.; Maity, A. C.; Das, N. K. J. Sulfur Chem. 2007, 28, 233.

S7

S8

3aN

N

S

Ph

H3 C

S9

3aN

N

S

Ph

H3 C

S10

3bN

N

S

Ph

S11

3bN

N

S

Ph

S12

3cN

N

S

Ph

n-Bu

S13

3cN

N

S

Ph

n-Bu

S14

3dN

N

S

Ph

S15

3dN

N

S

Ph

S16

N

N

S

Ph

3e

S17

N

N

S

Ph

3e

S18

N

N

S

Ph

Cl

3f

S19

N

N

S

Ph

Cl

3f

S20

N

N

S

Ph

Bn

3g

S21

N

N

S

Ph

Bn

3g

S22

N

N

S

Ph

CH3

3h

S23

3hN

N

S

Ph

CH3

S24

3iN

N

S

Ph

H3 C

S25

3iN

N

S

Ph

H3 C

S26

3jN

N

S

Ph

F

S27

3jN

N

S

Ph

F

S28

3kN

N

S

Ph

Cl

S29

3kN

N

S

Ph

Cl

S30

N

N

S

Ph

H3 CO

3l

S31

N

N

S

Ph

H3 CO

3l

S32

N

N

S

Ph

F3 CO

3m

S33

N

N

S

Ph

F3 CO

3m

S34

N

N

S

Ph

HO

3n

S35

N

N

S

Ph

HO

3n

S36

3oN

N

S

Ph

O2 N

S37

3oN

N

S

Ph

O2 N

S38

3pN

N

S

Ph

S39

3pN

N

S

Ph

S40

3qN

N

S

n-Bu

CH3

S41

3qN

N

S

n -Bu

CH3

S42

3rN

N

S

Bn

CH3

S43

3rN

N

S

Bn

CH3

S44

3sN

N

SO2 N

CH3

S45

3sN

N

SO2 N

CH3

3oN

N

S

BnCH3

S46

3tN

N

S

BnCH3

S47

3tN

N

S

BnCH3

S48

3pN

N

S

Bn

CF3

3uN

N

S

Bn

CF3

S49

3uN

N

S

Bn

CF3

S50

3vN

N

S

Bn

Cl

S51

3vN

N

S

Bn

Cl

S52

3wN

N

S

Cl

S53

3wN

N

S

Cl

S54

3xN

N

S

Bn

Cl

S55

3xN

N

S

Bn

Cl

S56

3yN

N

S

BnBr

S57

3yN

N

S

BnBr

S58

3zN

N

S

BnNO2

S59

3zN

N

S

BnNO2

3vN

N

S

BnS

S60

3a'N

N

S

BnS

S61

3a'N

N

S

BnS

S62

3b'N

N

S

Bn

S

S63

3b'N

N

S

Bn

S

S64

NH

SNH

NO2

III-1

S65

NH

SNH

NO2

III-1

S66

N

N

S4a

S67

N

N

S4a