Supporting Information

Synthesis, insecticidal sctivities and structure-activity relationship

study of dual chiral sulfiliminesSha Zhou*, Xiangde Meng, Ruyi Jin‡, Yi Ma, Yongtao Xie, Yu Zhao, Lixia Xiong, Zhengming Li*

National Pesticidal Engineering Centre (Tianjin), State Key Laboratory of Elemento-Organic Chemistry,

Collaborative Innovation Center of Chemical Science and Engineering (Tianjin),

College of Chemistry, Nankai University, Tianjin 300071, China

‡Shenzhen Neptunus Bioengineering Co.,LTD, Shenzhen, China 518057

Table of Contents

General procedure for compound 2·································································································S1General procedure for compound 4·································································································S1General procedure for compound 5·································································································S1General procedure for compound Ia-k·····························································································S2General procedure for compound IIa-k····························································································S2CoMFA analysis by SYBYL·········································································································S3HMRS··································································································································S4

The general procedure for compound 2

Synthesis of 1-(methylthio)propan-2-amine 2, pale yellow liquid, yield 57.8%, 1H NMR (400 MHz,

CDCl3-d6) δ 2.90 (dqd, J = 8.4, 6.3, 4.5 Hz, 1H, -CHNH2), 2.42 (dd, J = 13.2, 4.4 Hz, 1H, -SCH2-), 2.19

(dd, J = 13.2, 8.4 Hz, 1H, -SCH2-), 1.95 (s, 3H, -SCH3), 0.99 (d, J = 6.4 Hz, 3H, -C-CH3);

(S)-1-(methylthio)propan-2-amine 2, [α]20D=+30.13 (c=53.7, CHCl3)

The general procedure for compound 4

To a liquid mixture of 20ml of water and 20ml of t-butyl methyl ether were added successively

1.157g (10.8mmole) of o-toluidine , 3.8g (13 mmole) of heptafluoroisopropyl iodides, 2.2g (13

mmole) of sodium dithionite, 1,1g (13 mmole) of sodium hydrogen carbonate and 0.4g (1.2

mmole) of tetrabutylammonium hydrogen sulfate, and the resulting mixture was stirred at room

temperature for 8 hours. After separation of the organic layer, the aqueous layer was extracted

with 20ml of ethyl acetate, the extract was combined with the organic layer and washed

successively with 2N aqueous hydrochloric acid solution, 5% aqueous sodium carbonate solution

and saturated aqueous sodium chloride solution. The organic layer was dried with magnesium

sulfate, filtered and the organic solvent was distilled off under reduced pressure to obtain the

intended product 4.

The general procedure for compound 5

A mixture of aliphatic amine 2 (20 mmol) and triethylamine (20 mmol) in dichloromethane (50

ml) was slowly added to a solution of anhydride 1a-d(20 mmol) in dichloromethane (60 mL) at

room temperature. The reaction mixture was stirred for 16h, poured into water (50 mL), and

acidified with dilute hydrochloric acid. The aqueous layer was extracted with dichloromethane

(3*15 mL) and dried over anhydrous sodium sulfate. The solvent was removed under reduced

pressure and the residue was washed with a mixed solution of ether and hexane. 5 mmol of

phthalamic acid in 30 mL of dichloromethane was cooled with an ice bath while 5 mmol of

triethylamine was added dropwise with stirring. The solution was stirred and cooled to < 5 oC

followed by dropwise addition of 5 mmol of methylsulfonyl chloride at a rate so as to maintain the

temperature below 10 oC. The reaction mixture was stirred under ice bath. The progress of the

reaction was followed by TLC. The reaction solution was used in the subsequent reaction without

workup.

To the above reaction solution of 3a-d (3 mmol) in dichloromethane was added aromatic amine 4

(3 mmol) . The reaction mixture was stirred an additional hour under ice bath and then allowed to

warm to room temperature or reflux temperature. The progress of the reaction was followed by

TLC. The reaction solution was washed with dilute hydrochloric acid, water, an aqueous sodium

carbonate solution and water respectively and dried over anhydrous sodium sulfate. The solvent

was removed under reduced pressure, and the residue was purified by silica gel column

chromatography.

The general procedure for title compounds Ia-kA mixture of 1.0 mmol of 5a-d and 0.046g (1.1 mmol) of cyanamide in 20 mL of acetonitrile was

cooled below 0 oC. To this solution was added 0.322 g (1 mmol) of iodobenzene diacetate all at

once. The reaction mixture was allowed to stir below 0 oC for 10 min and slowly warmed to room

temperature over 1.5h, the progress of the reaction was followed by TLC. Excess oxidant was

destroyed by adding 5 mL of 2.5% aq sodium metabisulfite. The solution was washed with dilute

hydrochloric acid, water, an aqueous sodium carbonate solution and water respectively and dried

over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue

was purified by silica gel column chromagraphy.

The general procedure for title compounds IIa-k.To a solution of Ia-k (1 mmol) in dichloromethane, trifluoroacetic anhydride (TFAA) (0.630g, 3

mmol) was added dropwise over 15 min at room temperature. Then the reaction mixture was stirred

for another 0.5 h. The resulting mixture was washed with dilute hydrochloric acid, water, an aqueous

sodium carbonate solution and then water successively. The organic layer was dried (MgSO4) and

concentrated under reduced pressure to yield compounds IIa-k.

CoMFA Analysis by SYBYL

This is the result of CoMFA.Q2=0.596Compoments=4r2=0.928Standard Error of Estimate 0.11F=10.793

Steric 75.7%Electrostatic 24.3%

Ia 0.05Ib 0.75 *If 0.08Ig 0.51Ii 0.25IIa 0.15IIb 0.61IId 3.63IIg 0.12 *IIh 0.32IIj 0.65IIl 0.143IIa 0.163IIc 1.92

3IIIa 0.47 *3IIIc 6.36Compounds with *are in test dataset.HMRS for title compoundsIa and IIa

Ib and IIb

Ic and IIc

Id and IId

IIIa and IVa

IIIb and IVb

IIIc and IVc

IIId and IVd