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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