Supporting Information
Synthesis, insecticidal sctivities and structure-activity relationship study of dualchiralsulfilimines
Sha Zhou*, XiangdeMeng, Ruyi Jin‡, Yi Ma,YongtaoXie, Yu Zhao, LixiaXiong, 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························································S1
General procedure for compound 4························································S1
General procedure for compound 5························································S1
General procedure for compound Ia-k·······················································S2
General procedure for compound IIa-k······················································S2
CoMFA analysis by SYBYL·····························································S3
HMRS············································································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 with20ml 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 dropwisewith stirring. The solution was stirred and cooled to 5oC followed by dropwise addition of 5 mmol of methylsulfonyl chloride at a rate so as to maintain the temperature below 10oC. 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-k
A mixture of 1.0 mmol of 5a-d and 0.046g (1.1 mmol) of cyanamide in 20 mL of acetonitrile was cooled below 0oC. To this solution was added 0.322 g (1 mmol) of iodobenzenediacetate all at once. The reaction mixture was allowed to stir below 0oC 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=0.596
Compoments=4
r2=0.928
Standard Error of Estimate 0.11
F=10.793
Steric 75.7%
Electrostatic 24.3%
Ia0.05
Ib0.75 *
If0.08
Ig0.51
Ii0.25
IIa0.15
IIb0.61
IId3.63
IIg0.12 *
IIh0.32
IIj0.65
IIl0.14
3IIa0.16
3IIc1.92
3IIIa0.47 *
3IIIc6.36
Compounds with *are in test dataset.
HMRS for title compounds
Ia and IIa
Ib and IIb
Ic and IIc
Id and IId
IIIa and IVa
IIIb and IVb
IIIc and IVc
IIId and IVd