Insecticidal Activities of Chiral N-Trifluoroacetyl Sulfilimines as

Oct 28, 2014 - Synthesis, insecticidal activities and structure–activity relationship study of dual chiral sulfilimines. Sha Zhou , Xiangde Meng , R...
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Insecticidal Activities of Chiral N‑Trifluoroacetyl Sulfilimines as Potential Ryanodine Receptor Modulators Sha Zhou,† Yucheng Gu,§ Ming Liu,† Changchun Wu,† Sha Zhou,† Yu Zhao,† Zhehui Jia,† Baolei Wang,† Lixia Xiong,† Na Yang,† and Zhengming Li*,† †

State Key Laboratory of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, China § Syngenta Jealott’s Hill International Research Centre, Bracknell, Berkshire RG42 6EY, United Kingdom ABSTRACT: This is the first report of novel chiral N-trifluoroacetyl sulfilimines during research for new environmentally benign and ecologically safe novel insecticides with new modes of action. Four series of phthalamides containing 20 new structures were designed, synthesized, and evaluated against oriental armyworm (Pseudaletia separata Walker) and diamondback moth (Plutella xylostella (L.)) for their insecticidal activities. The target compounds were established by corresponding 1H NMR, HRMS (or elemental analysis), X-ray diffraction analysis, and optical polarimetry. Introduction of chiral N-trifluoroacetyl sulfiliminyl moieties into the new scaffolds showed that some target compounds possessed impressive activities as commercial flubendiamide. These N-trifluoroacetyl sulfilimines exhibited the sequence of activity against oriental armyworm as (Sc, Ss) ≥ (Sc, Rs) ≫ (Rc, Rs) > (Rc, Ss), in which the chiral carbon influenced the activities stronger than sulfur. For diamondback moth, compounds If, IIa, and IIc exhibited even stronger activity than flubendiamide; especially If displayed a death rate of 100% at 10−6 mg L−1, much better than that of flubendiamide (0% at 10−4 mg L−1). Comparative molecular field analysis calculation indicated that stereoisomers with Sc configurations containing more electronegative group as COCF3 are favorable to the insecticidal activity. The present work demonstrated that chiral N-trifluoroacetyl sulfilimines can be considered as potential insect ryanodine receptor modulators. From the standpoint of molecular design, it was concluded that the conventional second methyl group in the aliphatic amido side chain of dicarboxamide might not be a requisite in our research on novel sulfiliminyl insecticides. KEYWORDS: optically active, sulfiliminyl, insecticidal activity

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INTRODUCTION To discover new pesticides with novel modes of actions together with suitable environmental profiles tackling the issues of both resistance and highly demanding registration criteria, Nihon Nohyakuin in 1998 declared that some phthalamides1−5 exhibit excellent high activity against lepidopteran pests while being benign to our environment and ecological balance, among which flubendiamide (Figure 1A) was jointly developed with Bayer Co. for the market in 2007.6−13 Shortly after, DuPont Co. transformed one of the amide bonds into the new structures of anthranilamides. Thus, chlorantraniliprole (Figure 1B) and cyantraniliprole (Figure 1C)14−18 were discovered to exhibit better potency against a wide range of lepidopteran pests than flubendiamide. All of these compounds are highly potent activators targeting the ryanodine receptor (RyR). Our research group has previously reported novel optically active N-cyano sulfilimines with larvicidal activities. Several sulfilimine derivatives of structure (Figure 1D) reached the high activity of flubendiamide, with LC50 values of 0.0504 and 0.0699 mg L−1, respectively, lower than that of flubendiamide (0.1230 mg L−1).19,20 Considering the fluorine atom usually plays an active role in pharmaceutical and crop protection products,21−26 the introduction of a trifluoroacetyl group into the sulfiliminyl moiety with the replacement of cyano could bring changes in physical, chemical, and biological properties. On the basis of the above postulation, a series of novel optically active N-trifluoroacetyl sulfilimines were synthesized © 2014 American Chemical Society

via key intermediates N-cyano sulfilimines. All title compounds were characterized by 1H NMR, elemental analysis (or HRMS), and optical polarimetry. Comparative molecular field analysis (CoMFA) calculation was undertaken. In addition, a preliminary structure−activity relationship (SAR) was discussed.

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MATERIALS AND METHODS

Instruments and Materials. The melting points were determined on an X-4 binocular microscope melting point apparatus (Beijing Tech Instrument Co., Beijing, China) and were uncorrected. 1H NMR spectra were recorded at 300 MHz (Bruker AC-P 300 spectrometer) or 400 MHz (Bruker AV 400 spectrometer) in CDCl3 or DMSO-d6 solution with tetramethylsilane as internal standard, and chemical shifts (δ) were given in parts per million. Elemental analyses were performed on a Vario EL elemental analyzer. HRMS data were obtained on a Varian QFT-ESI instrument. Optical rotations were measured with a PerkinElmer 341 polarimeter at 20 °C. Reagents used were all of analytical grade. All solvents and liquid reagents were dried by standard methods and distilled before use. Commercial insecticide flubendiamide was used as a standard, which was synthesized according to procedures in the literature.3 Received: Revised: Accepted: Published: 11054

July 23, 2014 October 28, 2014 October 28, 2014 October 28, 2014 dx.doi.org/10.1021/jf503513n | J. Agric. Food Chem. 2014, 62, 11054−11061

Journal of Agricultural and Food Chemistry

Article

Figure 1. General Synthetic Procedures for Compounds 1a−g, 2a−f, 3a−c,e, and 4a−c,e. These phthalamide intermediates 1a−d,f, 2a− d,2f, 3a−c, 4a−c were synthesized according to the method reported in our previous publication (Scheme 1) .19 (S,R)-N2-(1-(N-Cyano-S-methylsulfinimidoyl)propan-2-yl)-N1-(2methyl-4-(perfluoropropan-2-yl)phenyl)phthalamide, 1e: white solid; yield 68.3%, mp 107−109 °C; 1H NMR (300 MHz, DMSO-d6) δ 10.00 (s, 1H), 8.74 (d, J = 6.7 Hz, 1H), 7.81−7.79 (d, J = 6.0 Hz, 1H), 7.68−7.54 (m, 6H), 4.32−4.24 (m, 1H), 3.25 (d, J = 7.0 Hz, 1H), 2.80 (s, 3H), 2.39 (s, 3H), 1.28 (d, J = 3.9 Hz, 3H). HRMS calcd for C23H21F7N4O2SH ([M + H]+), 551.1346; found, 551.1349. [α]20D = −64.2 (c 10, MeOH). (S,S)-N2-(1-(N-Cyano-S-methylsulfinimidoyl)propan-2-yl)-N1-(2methyl-4-(perfluoropropan-2-yl)phenyl)phthalamide, 2e: white solid; yield 31.7%; mp 114−116 °C; 1H NMR (400 MHz, DMSO-d6) δ 10.01 (s, 1H), 8.59 (d, J = 7.7 Hz, 1H), 7.80 (d, J = 8.2 Hz, 1H), 7.67− 7.53 (m, 6H), 4.33−4.25 (m, 1H), 3.28 (d, J = 8.7 Hz, 2H), 2.80 (s, 3H), 2.38 (s, 3H), 1.28 (d, J = 6.4 Hz, 3H). HRMS calcd for C23H21F7N4O2SH ([M + H]+), 551.1346; found, 551.1349. [α]20D = +76.0 (c 10, MeOH). (R,S)-N2-(1-(N-Cyano-S-methylsulfinimidoyl)propan-2-yl)-N1-(2methyl-4-(perfluoropropan-2-yl)phenyl)phthalamide,3e: white solid; yield 70.4%, mp 106−108 °C; 1H NMR (300 MHz, DMSO-d6) δ 10.00 (s, 1H), 8.74 (d, J = 6.7 Hz, 1H), 7.81−7.79 (d, J = 6.0 Hz, 1H), 7.68−7.54 (m, 6H), 4.32−4.24 (m, 1H), 3.25 (d, J = 7.0 Hz, 1H), 2.80 (s, 3H), 2.39 (s, 3H), 1.28 (d, J = 3.9 Hz, 3H). HRMS calcd for C23H21F7N4O2SH ([M + H]+), 551.1346; found, 551.1349. [α]20D = +63.9 (c 10, MeOH). (R,R)-N2-(1-(N-Cyano-S-methylsulfinimidoyl)propan-2-yl)-N1-(2methyl-4-(perfluoropropan-2-yl)phenyl)phthalamide, 4e: white solid; yield 29.6%; mp 115−116 °C; 1H NMR (400 MHz, DMSO-d6) δ 10.01 (s, 1H), 8.59 (d, J = 7.7 Hz, 1H), 7.80 (d, J = 8.2 Hz, 1H), 7.67− 7.53 (m, 6H), 4.33−4.25 (m, 1H), 3.28 (d, J = 8.7 Hz, 2H), 2.80 (s, 3H), 2.38 (s, 3H), 1.28 (d, J = 6.4 Hz, 3H). HRMS calcd for C23H21F7N4O2SH ([M + H]+), 551.1346; found, 551.1349. [α]20D = −75.8 (c 10, MeOH). (S,R)-N2-(1-(N-Cyano-S-methylsulfinimidoyl)propan-2-yl)-N1-(3(trifluoromethyl)phenyl)phthalamide,1g: white solid; yield 72.9%; mp 194−195 °C; 1H NMR (400 MHz, DMSO-d6) δ 10.64 (s, 1H), 8.81 (d, J = 6.9 Hz, 1H), 8.15 (s, 1H), 8.05 (d, J = 6.8 Hz, 1H), 7.93 (d, J = 7.4 Hz, 1H), 7.75 (d, J = 6.3 Hz, 1H), 7.59 (d, J = 6.7, 13.2 Hz, 1H), 7.46 (d, J = 6.6 Hz, 1H), 7.32 (d, J = 5.9, 12.4 Hz, 1H), 4.27−4.25 (m, 1H), 3.29−3.27 (m, 1H), 3.24−3.19 (m, 1H), 2.81 (s, 3H), 1.27 (d, J = 4.4 Hz, 3H). HRMS calcd for C20H18F3IN4O2SH ([M + H]+), 563.0220; found, 563.0227. [α]20D = −13.2 (c 10, MeOH). General Synthetic Procedure for Compounds Ia−g, IIa−f, IIIa−c,e, and IVa−c,e. To a solution of 1a−g, 2a−f, 3a−c,e, or 4a− c,e (1 mmol) in dichloromethane was added dropwise trifluoroacetic anhydride (TFAA) (0.630 g, 3 mmol) 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 Ia−g, IIa−f, IIIa−c,e, and IVa−c,e.27

Scheme 1

(S,R)-3-Iodo-N 2 -(1-(N-trifluoroacetyl-S-methylsulfinimidoyl)propan-2-yl)-N 1 -(2-methyl-4-(perfluoropropan-2-yl)phenyl)11055

dx.doi.org/10.1021/jf503513n | J. Agric. Food Chem. 2014, 62, 11054−11061

Journal of Agricultural and Food Chemistry

Article

phthalamide, Ia: white solid; yield 90.3%; mp 185−186 °C; 1H NMR (400 MHz, CDCl3-d6) δ 8.68 (s, 1H, Ar-NH), 7.93 (t, J = 9.3 Hz, 2H, Ar−H), 7.69 (d, J = 7.8 Hz, 1H, Ar−H), 7.57 (d, J = 7.6 Hz, 1H, −CNH), 7.44 (s, 1H, Ar−H), 7.31 (d, J = 8.5 Hz, 1H, Ar−H), 7.07 (t, J = 7.8 Hz, 1H, Ar−H), 4.53 (m, 1H, −N−CH), 3.38 (dd, J = 13.0, 8.5 Hz, 1H, −SCH2), 3.06 (dd, J = 13.0, 4.0 Hz, 1H, −SCH2), 2.37 (s, 3H, −SCH3), 2.34 (s, 3H, ArCH3), 1.32 (d, J = 6.8 Hz, 3H, −CCH3). Anal. calcd for C24H20F10IN3O3S: C, 38.57; H, 2.70; N, 5.62. Found: C, 39.48; H, 2.79; N, 5.50. [α]20D = −21.2 (c = 10, MeOH). (S,R)-3-Fluoro-N2-(1-(N-trifluoroacetyl-S-methylsulfinimidoyl)propan-2-yl)-N 1 -(2-methyl-4-(perfluoropropan-2-yl)phenyl)phthalamide, Ib: white solid; yield 89.6%; mp 115−117 °C; 1H NMR (400 MHz, DMSO-d6) δ 10.01 (s, 1H, Ar−NH), 8.67 (d, J = 8.0 Hz, 1H, −CNH), 7.76 (d, J = 8.3 Hz, 1H, Ar−H), 7.56 (m, 4H, Ar−H), 7.46 (d, J = 8.5 Hz, 1H, Ar−H), 4.29 (m, 1H, −N−CH), 2.94−2.89 (m, 1H, −SCH2), 2.77(dd, J = 13.0, 4.5 Hz, 1H, −SCH2), 2.47 (s, 3H, −SCH3), 2.37 (s, 3H, ArCH3), 1.23 (d, J = 6.6 Hz, 3H, −CCH3). HRMS calcd for C24H20F11N3O3SH ([M + H]+), 640.1123; found, 640.1129. [α]20D = −4.4 (c 0.05, EtOAc). (S,R)-3-Chloro-N2-(1-(N-trifluoroacetyl-S-methylsulfinimidoyl)propan-2-yl)-N 1 -(2-methyl-4-(perfluoropropan-2-yl)phenyl)phthalamide, Ic: white solid; yield 92.3%; mp 103−105 °C; 1H NMR (400 MHz, DMSO-d6) δ 10.06 (s, 1H, Ar−NH), 8.94 (d, J = 8.0 Hz, 1H, −CNH), 7.77 (d, J = 8.0 Hz, 2H, Ar−H), 7.70 (d, J = 7.9 Hz, 1H, Ar−H), 7.61−7.50 (m, 4H, Ar−H), 4.32 (m, 1H, −N−CH), 3.39 (m, 1H, −SCH2), 3.32−3.27 (m, 1H, −SCH2), 2.79 (s, 3H, −SCH3), 2.37 (s, 3H, ArCH3), 1.23 (d, J = 6.5 Hz, 3H, −CCH3). Anal. calcd for C24H20ClF10N3O3S: C, 43.95; H, 3.07; N, 6.41. Found: C, 44.05; H, 3.15; N, 6.63. [α]20D = −3.8 (c 1, MeOH). (S,R)-3-Nitro-N 2 -(1-(N-trifluoroacetyl-S-methylsulfinimidoyl)propan-2-yl)-N 1 -(2-methyl-4-(perfluoropropan-2-yl)phenyl)phthalamide, Id: white solid; yield 89.8%; mp 117−119 °C; 1H NMR (400 MHz, DMSO-d6) δ 10.22 (s, 1H, Ar−NH), 9.05 (d, J = 7.6 Hz, 1H, −CNH), 8.27 (d, J = 6.9 Hz, 1H), 8.12 (d, J = 7.4 Hz, 1H, Ar− H), 7.84 (m, 2H, Ar−H), 7.56 (m, 2H, Ar−H), 4.28 (m, 1H, −N− CH), 3.32−3.25 (m, 2H, −SCH2), 2.78 (s, 3H, −SCH3), 2.40 (s, 3H, ArCH3), 1.21 (s, 3H, −CCH3). Anal. calcd for C24H20F10N4O5S: C, 43.25; H, 3.02; N, 8.48. Found: C, 43.09; H, 2.98; N, 8.48. [α]20D = −15.8 (c 4.2, EtOAc). (S,R)-N1-(2-Methyl-4-(perfluoropropan-2-yl)phenyl)-N2-(1-(N-trifluoroacetyl-S-methylsulfinimidoyl)propan-2-yl)phthalamide, Ie: white solid; yield 93.2%; mp 88−90 °C; 1H NMR (400 MHz, DMSO-d6) δ 10.01 (s, 1H), 8.79 (d, J = 8.3 Hz, 1H), 7.81 (d, J = 8.8 Hz, 1H), 7.70− 7.68 (m, 1H), 7.61−7.58 (m, 3H), 7.53−7.51 (m, 2H), 4.40−4.31 (m, 1H), 3.42 (dd, J = 12.6, 8.8 Hz, 2H), 2.85 (s, 3H), 2.38 (s, 3H), 1.27 (d, J = 6.7 Hz, 3H). HRMS calcd for C24H21F10N3O3SH ([M + H]+), 622.1217; found, 622.1220. [α]20D = −15.6 (c 10, MeOH). (S,R)-3-Bromo-N2-(1-(N-trifluoroacetyl-S-methylsulfinimidoyl)propan-2-yl)-N 1 -(2-methyl-4-(perfluoropropan-2-yl)phenyl)phthalamide, If: white solid; yield 91.2%; mp 116−117 °C; 1H NMR (400 MHz, DMSO-d6) δ 10.03 (d, J = 13.6 Hz, 1H, Ar−NH), 8.92 (t, J = 8.9 Hz, 1H, −CNH), 7.85 (d, J = 7.9 Hz, 1H, Ar−H), 7.82−7.75 (m, 2H, Ar−H), 7.70 (d, J = 7.9 Hz, 1H, Ar−H), 7.62−7.56 (m, 1H, Ar−H), 7.53 (d, J = 14.0 Hz, 2H, Ar−H), 4.33 (m, 1H, −N−CH), 3.38 (d, J = 12.7 Hz, 1H, −SCH2), 3.32−3.27 (m, 1H, −SCH2), 2.79 (s, 3H, −SCH3), 2.37 (s, 3H, ArCH3)), 1.24 (d, J = 6.6 Hz, 3H, −CCH3). HRMS calcd for C24H20BrF10N3O3SH ([M + H]+), 700.0332; found, 700.0334. [α]20D = −2.4 (c 1, MeOH). (S,R)-N2-(1-(N-Trifluoroacetyl-S-methylsulfinimidoyl)propan-2yl)-N1-(3-(trifluoromethyl)phenyl)phthalamide, Ig: white solid; yield 90.9%; mp 188−191 °C; 1H NMR (400 MHz, DMSO-d6) δ 10.63 (s, 1H), 8.81 (d, J = 8.0 Hz, 1H), 8.15 (s, 1H), 8.05 (d, J = 7.8 Hz, 1H), 7.94 (d, J = 7.9 Hz, 1H), 7.76 (d, J = 7.5 Hz, 1H), 7.58 (t, J = 7.8 Hz, 1H), 7.45 (d, J = 7.3 Hz, 1H), 7.31 (t, J = 7.7 Hz, 1H), 4.31 (d, J = 6.2 Hz, 1H), 3.46−3.39 (m, 1H), 3.28 (dd, J = 12.5, 5.2 Hz, 1H), 2.84 (s, 3H), 1.25 (d, J = 6.3 Hz, 3H). HRMS calcd for C21H18F6IN3O3SH ([M + H]+), 634.0081; found, 634.0081. [α]20D = +50.6 (c 10, EtOA). (S,S)-3-Iodo-N 2 -(1-(N-trifluoroacetyl-S-methylsulfinimidoyl)propan-2-yl)-N 1 -(2-methyl-4-(perfluoropropan-2-yl)phenyl)phthalamide, IIa: white solid, yield 89.7%; mp 142−144 °C; 1H NMR

(400 MHz, DMSO-d6) δ 9.99 (s, 1H, Ar−NH), 8.70 (d, J = 7.8 Hz, 1H, −CNH), 8.04 (d, J = 7.8 Hz, 1H, Ar−H), 7.78 (t, J = 6.8 Hz, 2H, Ar−H), 7.52 (d, J = 9.2 Hz, 2H, Ar−H), 7.31 (t, J = 7.8 Hz, 1H, Ar− H), 4.32 (dt, J = 13.8, 6.8 Hz, 1H, −N−CH), 3.32 (d, J = 6.7 Hz, 2H, −SCH2), 2.74 (s, 3H, −SCH3), 2.36 (s, 3H, ArCH3), 1.29 (d, J = 6.7 Hz, 3H, ArCH3). HRMS calcd for C24H20F10IN3O3SH ([M + H]+), 748.0183; found, 748.0179. [α]20D = +9.8 (c 1, MeOH). (S,S)-3-Fluoro-N2 -(1-(N-trifluoroacetyl-S-methylsulfinimidoyl)propan-2-yl)-N 1 -(2-methyl-4-(perfluoropropan-2-yl)phenyl)phthalamide, IIb: white solid; yield 90.4%; mp 101−102 °C; 1H NMR (400 MHz, DMSO-d6) δ 10.06 (s, 1H, Ar−NH), 8.76 (d, J = 7.8 Hz, 1H, −CNH), 7.75 (d, J = 6.7 Hz, 2H, Ar−H), 7.68 (d, J = 7.7 Hz, 1H, Ar−H), 7.55 (dd, J = 21.9, 9.3 Hz, 3H, Ar−H), 4.33 (m, 1H, −N− CH), 3.32−3.30 (m, 2H, −SCH2), 2.76 (s, 3H, −SCH3), 2.36 (s, 3H, ArCH3), 1.25 (d, J = 6.3 Hz, 3H, −CCH3). HRMS calcd for C24H20F11N3O3SH ([M + H]+), 640.1123; found, 640.1129. [α]20D = +26.8 (c 3, MeOH). (S,S)-3-Chloro-N2-(1-(N-trifluoroacetyl-S-methylsulfinimidoyl)propan-2-yl)-N 1 -(2-methyl-4-(perfluoropropan-2-yl)phenyl)phthalamide, IIc: white solid, yield 88.8%; mp 112−114 °C; 1H NMR (400 MHz, DMSO-d6) δ 10.07 (s, 1H, Ar−NH), 8.77 (d, J = 7.9 Hz, 1H, −CNH), 7.75 (t, J = 6.5 Hz, 2H), 7.69 (d, J = 8.0 Hz, 1H, Ar−H), 7.56 (dd, J = 21.8, 9.1 Hz, 4H, Ar−H), 4.33 (dd, J = 13.2, 6.9 Hz, 1H, −N−CH), 3.36 (m, 2H, −SCH2), 2.77 (s, 3H, −SCH3), 2.37 (s, 3H, ArCH3), 1.26 (d, J = 6.6 Hz, 3H, −CCH3). HRMS calcd for C24H20ClF10N3O3SH ([M + H]+), 656.0827; found, 656.0835. [α]20D = +10.6 (c 3, MeOH). (S,S)-3-Nitro-N 2 -(1-(N-trifluoroacetyl-S-methylsulfinimidoyl)propan-2-yl)-N 1 -(2-methyl-4-(perfluoropropan-2-yl)phenyl)phthalamide, IId: white solid; yield 90.2%; mp 124−126 °C; 1H NMR (400 MHz, DMSO-d6) δ 10.23 (s, 1H, Ar−NH), 8.89 (d, J = 7.6 Hz, 1H, −CNH), 8.25 (d, J = 8.1 Hz, 1H, Ar−H), 8.11 (d, J = 7.4 Hz, 1H, Ar−H), 7.83 (t, J = 8.0 Hz, 2H, Ar−H), 7.54 (d, J = 8.2 Hz, 2H, Ar− H), 4.32−4.24 (m, 1H, −N−CH), 3.29 (d, J = 6.7 Hz, 2H, −SCH2), 2.74 (s, 3H, −SCH3), 2.39 (s, 3H, ArCH3), 1.24 (d, J = 6.6 Hz, 3H, −CCH3). Aanl. calcd for C24H20F10N4O5S: C, 43.25; H, 3.02; N, 8.48. Found: C, 43.09; H, 2.98; N, 8.48. [α]20D = +30.2 (c 2, MeOH). (S,S)-N1-(2-Methyl-4-(perfluoropropan-2-yl)phenyl)-N2-(1-(N-trifluoroacetyl-S-methylsulfinimidoyl)propan-2-yl)phthalamide, IIe: white solid; yield 93.2%; mp 84−86 °C; 1H NMR (400 MHz, DMSO-d6) δ 10.00 (s, 1H), 8.59 (d, J = 8.0 Hz, 1H), 7.79 (d, J = 8.5 Hz, 1H), 7.68−7.66 (m, 1H), 7.59 (d, J = 5.7 Hz, 3H), 7.52−7.50 (m, 2H), 4.37−4.29 (m, 1H), 3.39 (d, J = 6.2 Hz, 2H), 2.82 (s, 3H), 2.37 (s, 3H), 1.28 (d, J = 6.7 Hz, 3H). HRMS calcd for C24H21F10N3O3SH ([M + H]+), 622.1217; found, 622.1220. [α]20D = +41.2 (c 2, MeOH). (S,S)-3-Bromo-N2-(1-(N-trifluoroacetyl-S-methylsulfinimidoyl)propan-2-yl)-N 1 -(2-methyl-4-(perfluoropropan-2-yl)phenyl)phthalamide, IIf: white solid; yield 28.8%; mp 119−123 °C; 1H NMR (400 MHz, DMSO-d6) δ 10.04 (d, J = 10.7 Hz, 1H, Ar−NH), 8.75 (t, J = 8.0 Hz, 1H, −CNH), 7.85−7.66 (m, 3H, Ar−H), 7.60−7.47 (m, 3H, Ar−H), 4.38−4.29 (m, 1H, −N−CH), 3.31 (d, J = 13.5 Hz, 2H, −SCH2), 2.77 (s, 3H, −SCH3), 2.36 (s, 3H, ArCH3), 1.26 (d, J = 6.6 Hz, 3H, −CCH3). HRMS calcd for C24H20BrF10N3O3SH ([M + H]+), 700.0332; found, 700.0334. [α]20D = +10.0 (c 1, MeOH). (R,S)-3-Iodo-N 2 -(1-(N-trifluoroacetyl-S-methylsulfinimidoyl)propan-2-yl)-N 1 -(2-methyl-4-(perfluoropropan-2-yl)phenyl)phthalamide, IIIa: white solid; yield 89.7%; mp 184−186 °C; 1H NMR (400 MHz, CDCl3-d6) δ 8.68 (s, 1H, Ar−NH), 7.93 (t, J = 9.3 Hz, 2H, Ar−H), 7.69 (d, J = 7.8 Hz, 1H, −CNH), 7.57 (d, J = 7.6 Hz, 1H, Ar−H), 7.44 (s, 1H, Ar−H), 7.31 (d, J = 8.5 Hz, 1H, Ar−H), 7.07 (t, J = 7.8 Hz, 1H, Ar−H), 4.53 (m, 1H, −N−CH), 3.38 (dd, J = 13.0, 8.5 Hz, 1H, −SCH2), 3.06 (dd, J = 13.0, 4.0 Hz, 1H, −SCH2), 2.37 (s, 3H, −SCH3), 2.34 (s, 3H, ArCH3), 1.32 (d, J = 6.8 Hz, 3H, −CCH3). Anal. calcd for C24H20F10IN3O3S: C, 38.57; H, 2.70; N, 5.62. Found: C, 39.48; H, 2.79; N, 5.50. [α]20D = +20.8 (c 5, MeOH). (R,S)-3-Fluoro-N2-(1-(N-trifluoroacetyl-S-methylsulfinimidoyl)propan-2-yl)-N 1 -(2-methyl-4-(perfluoropropan-2-yl)phenyl)phthalamide, IIIb: white solid; yield 90.6%; mp 116−118 °C; 1H NMR (400 MHz, DMSO-d6) δ 10.02 (s, 1H, Ar−NH), 8.68 (d, J = 8.0 Hz, 1H, −CNH), 7.77 (d, J = 8.3 Hz, 1H, Ar−H), 7.57 (m, 4H, Ar− 11056

dx.doi.org/10.1021/jf503513n | J. Agric. Food Chem. 2014, 62, 11054−11061

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H), 7.47 (d, J = 8.5 Hz, 1H, Ar−H), 4.30 (m, 1H, −N−CH), 2.95− 2.90 (m, 1H, −SCH2), 2.78 (dd, J = 13.0, 4.5 Hz, 1H, −SCH2), 2.48 (s, 3H, −SCH3), 2.38 (s, 3H, ArCH3), 1.23 (d, J = 6.6 Hz, 3H, −CCH3). HRMS calcd for C24H20F11N3O3SH ([M + H]+), 640.1123; found, 640.1129. [α]20D = +4.6 (c 0.05, EtOAc). (R,S)-3-Chloro-N2-(1-(N-trifluoroacetyl-S-methylsulfinimidoyl)propan-2-yl)-N 1 -(2-methyl-4-(perfluoropropan-2-yl)phenyl)phthalamide, IIIc: white solid; yield 89.1%; mp 104−105 °C; 1H NMR (400 MHz, DMSO-d6) δ 10.06 (s, 1H, Ar−NH), 8.94 (d, J = 8.0 Hz, 1H, −CNH), 7.77 (d, J = 8.0 Hz, 2H, Ar−H), 7.70 (d, J = 7.9 Hz, 1H, Ar−H), 7.61−7.50 (m, 4H, Ar−H), 4.32 (m, 1H, −N−CH), 3.39 (m, 1H, −SCH2), 3.32−3.27 (m, 1H, −SCH2), 2.79 (s, 3H, −SCH3), 2.37 (s, 3H, ArCH3), 1.23 (d, J = 6.5 Hz, 3H, −CCH3). Anal. calcd for C24H20ClF10N3O3S: C, 44.12; H, 3.17; N, 6.48. Found: C, 44.05; H, 3.15; N, 6.63. [α]20D = +3.6 (c 1, MeOH). (R,S)-N1-(2-Methyl-4-(perfluoropropan-2-yl)phenyl)-N2-(1-(N-trifluoroacetyl-S-methylsulfinimidoyl)propan-2-yl)phthalamide, IIIe: white solid; yield 92.8%; mp 87−88 °C; 1H NMR (400 MHz, DMSO-d6) δ 10.01 (s, 1H), 8.79 (d, J = 8.3 Hz, 1H), 7.81 (d, J = 8.8 Hz, 1H), 7.70−7.68 (m, 1H), 7.61−7.58 (m, 3H), 7.53−7.51 (m, 2H), 4.40−4.31 (m, 1H), 3.42 (dd, J = 12.6, 8.8 Hz, 2H), 2.85 (s, 3H), 2.38 (s, 3H), 1.27 (d, J = 6.7 Hz, 3H). HRMS calcd for C24H21F10N3O3SH ([M + H]+), 622.1217; found, 622.1220. [α]20D = +15.2 (c 10, MeOH). (R,R)-3-Iodo-N 2 -(1-(N-trifluoroacetyl-S-methylsulfinimidoyl)propan-2-yl)-N 1 -(2-methyl-4-(perfluoropropan-2-yl)phenyl)phthalamide, IVa: white solid; yield 91.7%; mp 140−142 °C; 1H NMR (400 MHz, CDCl3-d6) δ 8.43 (s, 1H, Ar−NH), 8.12 (d, J = 8.4 Hz, 1H, Ar−H), 7.94 (d, J = 7.4 Hz, 1H, −CNH), 7.69 (d, J = 7.6 Hz, 1H, Ar−H), 7.44 (d, J = 8.1 Hz, 2H, Ar−H), 7.33 (d, J = 7.3 Hz, 1H, Ar− H), 7.18 (t, J = 7.9 Hz, 1H, Ar−H), 4.19 (m, 1H, −N−CH), 3.48 (dd, J = 12.9, 8.7 Hz, 1H, −SCH2), 3.06 (dd, J = 12.9, 3.5 Hz, 1H, −SCH2), 2.40 (s, 3H, −SCH3), 2.36 (s, 3H, ArCH3), 1.50 (d, J = 6.9 Hz, 3H, −CCH3). HRMS calcd for C24H20F10IN3O3SH ([M + H]+), 748.0183; found, 748.0179. [α]20D = −9.6 (c 1, MeOH). (R,R)-3-Fluoro-N2-(1-(N-trifluoroacetyl-S-methylsulfinimidoyl)propan-2-yl)-N 1 -(2-methyl-4-(perfluoropropan-2-yl)phenyl)phthalamide, IVb: white solid; yield 89.7%; mp 100−101 °C; 1H NMR (400 MHz, DMSO-d6) δ 10.06 (s, 1H, Ar−NH), 8.76 (d, J = 7.8 Hz, 1H, −CNH), 7.75 (d, J = 6.7 Hz, 2H, Ar−H), 7.68 (d, J = 7.7 Hz, 1H, Ar−H), 7.55 (dd, J = 21.9, 9.3 Hz, 3H, Ar−H), 4.33 (m, 1H, −N−CH), 3.32−3.30 (m, 2H, −SCH2), 2.76 (s, 3H, −SCH3), 2.36 (s, 3H, ArCH3), 1.25 (d, J = 6.3 Hz, 3H, −CCH3). HRMS calcd for C24H20F11N3O3SH ([M + H]+), 640.1123; found, 640.1129. [α]20D = −26.4 (c 3, MeOH). (R,R)-3-Chloro-N2-(1-(N-trifluoroacetyl-S-methylsulfinimidoyl)propan-2-yl)-N 1 -(2-methyl-4-(perfluoropropan-2-yl)phenyl)phthalamide, IVc: white solid; yield 90.1%; mp 113−114 °C; 1H NMR (400 MHz, DMSO-d6) δ 10.07 (s, 1H, Ar−NH), 8.77 (d, J = 7.9 Hz, 1H, −CNH), 7.75 (t, J = 6.5 Hz, 2H), 7.69 (d, J = 8.0 Hz, 1H, Ar−H), 7.56 (dd, J = 21.8, 9.1 Hz, 4H, Ar−H), 4.33 (dd, J = 13.2, 6.9 Hz, 1H, −N−CH), 3.36 (m, 2H, −SCH2), 2.77 (s, 3H, −SCH3), 2.37 (s, 3H, ArCH3), 1.26 (d, J = 6.6 Hz, 3H, −CCH3). HRMS calcd for C24H20ClF10N3O3SH ([M + H]+), 656.0827; found, 656.0835. [α]20D = −10.4 (c 3, MeOH). (R,R)-N1-(2-Methyl-4-(perfluoropropan-2-yl)phenyl)-N2-(1-(N-trifluoroacetyl-S-methylsulfinimidoyl)propan-2-yl)phthalamide, IVe: white solid; yield 93.2%; mp 85−86 °C; 1H NMR (400 MHz, DMSO-d6) δ 10.00 (s, 1H), 8.59 (d, J = 8.0 Hz, 1H), 7.79 (d, J = 8.5 Hz, 1H), 7.68−7.66 (m, 1H), 7.59 (d, J = 5.7 Hz, 3H), 7.52−7.50 (m, 2H), 4.37−4.29 (m, 1H), 3.39 (d, J = 6.2 Hz, 2H), 2.82 (s, 3H), 2.37 (s, 3H), 1.28 (d, J = 6.7 Hz, 3H). HRMS calcd for C24H21F10N3O3SH ([M + H]+), 622.1217; found, 622.1220. [α]20D = −40.8 (c 10, MeOH). X-ray Diffraction. A colorless crystal Ig suitable for X-ray diffraction study was cultivated in the test tube from DMSO by selfvolatilization. A crystal with dimensions of 0.20 mm × 0.15 mm × 0.10 mm was mounted on a Bruker SMART 1000 CCD diffractometer equipped with a graphite-monochromatic Mo Kα radiation (λ = 0.71073 Å). Intensity data were collected at 293(2) K by using a

multiscan mode in the range of 3.05° ≤ θ ≤ 25.50° with the following index ranges: −16 ≤ h ≤ 16, −16 ≤ k ≤ 16, and −27 ≤ l ≤ 26. A total of 31784 reflections were collected, and 4768 were independent (Rint = 0.0441), of which 4091 with I > 2σ(I) were observed. X-ray singlecrystal diffraction is shown in Figure 2 with the following

Figure 2. Crystal structure of compound Ig.

crystallographic parameters: a = 13.998(2) Å, b = 13.998 (2) Å, c = 22.660(5) Å, α = 90°, β = 90°, γ = 120°, V = 3845.4(11) Å3, Z = 4, Dc = 1.644 mg m−3, μ = 1.401 mm−1, F (000) = 1878, R = 0.0539, wR = 0.1349, final R factor = 4.54%, final wR factor = 12.87%, absolute structure parameter = −0.02 (3). The crystal structure was solved by direct methods with SHELXS-9728 and refined by full-matrix leastsquares refinements based on F2 with SHELXL-97. All non-hydrogen atoms were refined anisotropically, and all hydrogen atoms were located in the calculated positions and refined with a riding model. Biological Assay. All bioassays were performed on representative test organisms reared in the laboratory. The bioassay was repeated at 25 ± 1 °C according to the statistical requirements. Assessments were made on a dead/alive basis, and mortality rates were corrected using Abbott’s formula.29 Evaluations were based on a percentage scale of 0−100, in which 0 = no activity and 100 = total control. The standard deviations of the tested biological values were ±5%. LC50 values were calculated by probit analysis.30 Larvicidal Activity against Oriental Armyworm (Pseudaletia separata Walker). The larvicidal activity of title compounds and the standard flubendiamide against oriental armyworm was tested according to the leaf-dip method using the reported procedure.31 The insecticidal activity is summarized in Table 1. LC50 values of compounds Ia,b,d, IIb,d,f, IIIa,b, IVa, and flubendiamide against oriental armyworm are listed in Table 2. Larvicidal Activity against Diamondback Moth (Plutella xylostella L.). The larvicidal activity of title compounds and flubendiamide against diamondback moth was tested by the leaf-dip method using the reported procedure.32,33 The insecticidal activity is summarized in Table 3.

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RESULTS AND DISCUSSION Synthesis. The synthesis of N-trifluoroacetyl sulfilimines was achieved by the key intermediates N-cyano sulfilimines as shown in Scheme 1. The N-cyano group was proved to be easily cleaved upon treatment with TFAA at room temperature. Compared with N-cyano sulfilimines, these N-trifluoroacetyl sulfiliminyl derivatives displayed better solubility and improved hydrophobicity. 11057

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Table 1. Insecticidal Activity of Compounds Ia−f, IIa−f, IIIa−c,e, IVa−c,e and Flubendiamide against Oriental Armyworm larvicidal activity (%) at concn of compd

200 mg L−1

Ia 100 Ib 100 Ic 100 Id 100 Ie 100 If 100 IIa 100 IIb 100 IIc 100 IId 100 IIe 100 IIf 100 IIIa 100 IIIb 100 IIIc 100 IIIe 100 IVa 100 IVb 100 IVc 100 IVe 100 flubendiamide

100 mg L−1

50 mg L−1

25 mg L−1

10 mg L−1

5 mg L−1

2.5 mg L−1

1 mg L−1

0.5 mg L−1

0.25 mg L−1

0.1 mg L−1

100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100

100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 60 100 100 100 60 100

100 100 100 100 100 100 100 100 100 100 60 100 100 100 100

100 100 100 100 100 100 100 100 100 100 40 100 100 40 100

100 100 100 60 60 100 100 100 100 100

100 100 100

100 100 100

100 40 100

100

60

100 100 100 100 100

70 100 100 100 100

100 70 100 20

100

100 100

100 100

100 100

100 10

100

30

100 100 100

100 50 100

100

100

100

40

20

10

100

100

20

100

100

100

100

100

100

100

50

60

60

60

60

Table 2. LC50 Values of Compounds Ia,b,d, IIa,b,d,f, IIIa,b, IVa, and Flubendiamide against Oriental Armyworm LC50(mg/L) y = a + bx

compd y y y y y y y y y y y

Ia Ib Id IIa IIb IId IIf IIIa IIIb IVa flubendiamide

= = = = = = = = = = =

14.4459 + 10.9593x 6.1688 + 4.9956x 3.2828 + 3.0490x 8.6832 + 3.7658x 6.6165 + 3.4223x 6.4616 + 7.3125x 11.0336 + 7.2617x 6.4647 + 8.6005x 2.6064 + 2.1918x 5.5815 + 2.0234x 7.4237 + 2.6428x

R

LC50

LC95

0.9468 0.9988 0.9399 0.9914 0.9735 0.9782 0.9913 0.9875 0.9871 0.9491 0.9945

0.1374 0.5835 3.6577 0.1052 0.3370 0.6311 0.1476 0.6756 12.3621 0.5160 0.1230

0.1942 1.2453 12.6672 0.2876 1.0193 1.0594 0.2487 1.0494 69.5919 3.3537 0.5160

Table 3. Insecticidal Activity of Compounds Ia,f, IIa−c, and Flubendiamide against Diamondback Moth larvicidal activity (%) at concn of compd

1 mg L−1

10−1 mg L−1

10−2 mg L−1

10−3mg L−1

100 100 100 100 100

100 100 100 100 100 100

90 100 100 100 100 100

40 100 100 40 100 50

Ia If IIa IIb IIc flubendiamide

10−4 mg L−1

10−5 mg L−1

10−6 mg L−1

10−7 mg L−1

100 100

100 40

100

70

100 0

100

80

20

bond lengths and bond angles of the benzene ring, amide group, CF3 group, or other bonds are within normal ranges.34−38 The S(1)N(2) bond [1.679(6)Å] is longer than the general CN double-bond length of 1.27 Å. The torsion angle of N(2)−S(1)−C(10)−C(8) is −93.4(6)°. As shown in Figure 2, the two phenyl rings are nearly vertical with a quite small dihedral angle (θ) of 40.8°. In the intermolecular face-to-face π−π stacking pattern of the title compound, it is worth mentioning that the two molecules of each stacking unit (C15−C21) are cetro-symmetric, which can be proved by the

The novel structures of these title compounds were characterized by melting point, 1H NMR, elemental analysis (or high-resolution mass spectrometry), and optical polarimetry. The chemical shifts of the active proton signals in the anilide moiety were at 10.01−10.22 ppm in DMSO-d6. However, the active proton signals of −NHCO− on the amide bridge in the aliphatic amide moiety were observed at δ 8.67−9.05 and δ 8.70−8.89 in DMSO-d6, respectively. Crystal Structure Analysis. The molecular structure of the title compound is shown in Figure 2. Generally, the average 11058

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methyl group in the aliphatic amido side chain of dicarboxamide might not be requisite during our molecular design stragety. From Table 2, it was found that the LC50 value of IIa was 0.1052 mg L−1, slightly lower than that of flubendiamide (0.1230 mg L−1). In addition, the LC50 values of compounds Ia, IIb, and IIf were 0.1374, 0.3374, and 0.1476 mg L−1, respectively. Larvicidal Activity against Diamondback moth. The larvicidal activities of compounds Ia, If, and IIa−c and flubendiamide against diamondback moth are listed in Table 3. From that table, we observed that most compounds exhibited excellent activities. Compared with different substituents I, F, and Cl in the phthaloyl moiety of the title compounds, Br revealed the best activity, a death rate of 100% at 10−6 mg L−1, which is a much better activity than that of flubendiamide (0% at 10−4 mg L−1) with a striking difference of >100-fold. Also, IIa and IIc gave higher activity than flubendiamide; the larvicidal activities of IIa and IIc were 40% at 10−5 mg L−1 and 80% at 10−6 mg L−1, respectively, better than that of flubendiamide. Whereas Ia and IIb reached the same activity level as flubendiamide. The bioassay results indicated that chiral dicarboxamide scaffolds containing N-trifluoroacetyl sulfiliminyl moiety were favorable to improve the larvicidal activity toward the diamondback moth. CoMFA Analysis by SYBYL. The CoMFA method is widely used in drug design because it allows for rapid prediction of QSAR of newly designed molecules.40−43 Using SYBYL,44 a brief CoMFA is taken for two data sets. Compounds in data set 1 are Ia,b,d, IIb,d,f, IIIa,b, and IVa. In addition to compounds in data set 1, compounds with N-cyano sulfiliminyl substituted in the aliphatic amide moiety are included in data set 2. The conformations of all molecules are optimized with Tripos force field and Gasteiger−Hukel charges, whereas the activity data are reported as the negative logarithms of LC50. Detailed CoMFA results for the two data sets are shown in Figures 3 and 4, respectively. The result for data set 1 draws similar conclusions as in a previous paper.19 The green area near the I substituent suggests that a bulkier group is favorable. The small yellow area indicates a less bulky substituent enhances activity. Thus, the molecules

relative position of the two phenyl rings of the two molecules. The crystal packing structure demonstrates the existence of three intermolecular hydrogen bond and an intramolecular hydrogen bond: N−H---O and N−H---I. These interactions are estimated to play a role in stabilizing the crystal structure. Structure−Activity Relationship (SAR). Larvicidal Activity against Oriental Armyworm. The larvicidal activity of compounds Ia−f, IIa−f, IIIa−c,e, and IVa−c,e against oriental armyworm are listed in Table 1. Most title compounds exhibited good to excellent activity against oriental armyworm. Generally speaking, these stereoisomers exhibited different impacts on biological activity following the sequence (Sc, Ss) ≥ (Sc, Rs) ≫ (Rc, Rs) > (Rc, Ss), which is not in accordance with N-cyano sulfiliminyl structures reported in our previous publication as ((Sc, Ss) ≥ (Sc, Rs) ≫ (Rc, Ss) > (Rc, Rs)).19 As shown in Table 1, for example, IIa (Sc, Ss) showed 60% insecticidal activity at 0.1 mg L−1, whereas IIIa (Rc, Ss) gave a death rate of 10% at only 0.5 mg L−1. As seen in Rs configurations, Ia (Sc, Rs) (100%) showed better insecticidal activity than IVa (Rc, Rs) (20%) at a concentration of 0.25 mg L−1. These observations indicated that activities varied significantly depending upon carbon and sulfur chirality. As seen in comparison with other structures in the four configurations, II (Sc, Ss) was most active, followed by I (Sc, Rs) and IV (Rc, Rs), whereas III (Rc, Ss) was almost inactive. It was further concluded that a reasonable coordination of both carbon and sulfur chirality accounted for the improvement of insecticidal activity and that a possible synergistic effect was involved. In comparison, in some cases these diastereoisomers with Sc configurations (Ia vs IIa, Ib vs IIb, and Ic vs IIc), Rc configurations (IIIb vs IVb and IIIe vs IVe) showed similar activities. Whereas IIf (Sc, Ss) displayed 30% insecticidal activity at 0.1 mg L−1, the larvicidal activity of If (Sc, Rs) was 70% at 1 mg L−1, and IId (Sc, Ss) showed better activity than Id (Sc, Rs). These observations showed that Ss configurations gave higher activity than Rs counterparts in these Sc configurations. However, in other cases, Rs configurations showed better activity than Ss counterparts in these Rc configurations, such as IVa versus IIIa, IVb versus IIIb, and IVc versus IIIc. Carbon chirality has a stronger influence on the activity than sulfur, as shown in Rs configurations (Ia vs IIIa, Ib vs IIIb, Ic vs IIIc, and Ie vs IIIe) and in Ss configurations (IIa vs IVa, IIb vs IVb, IIc vs IVc, and IIe vs IVe). As shown in Table 1, all compounds showed a mortality of 100% at 10 mg L−1, except IIe, IIIb, IIIe, IVb, and IVe. Particularly, Ia, Ic, IIa, IIc, IIf, and IVa exhibited 100% larvicidal activities even at 1 mg L−1. It is worth noting that Ia, IIa, and IIf showed activities as excellent as that of flubendiamide. Furthermore, the iodine substituent in each configuration showed the best larvicidal activity, which was consistent with the previous paper.26 Br substituent as well as Cl, NO2, F, and H possessed inferior insecticidal activity against oriental armyworm. Compared with N-cyanosulfilimines,19 the results of larvicidal activity against oriental armyworm implied that the introduction of the N-trifluoroacetyl group was essential for improvement of larvicidal activity. This is probably due to these N-trifluoroacetyl sulfiliminyl derivatives displaying better solubility and improved hydrophobicites. In comparison with our previous research,39 N-trifluoroacetyl sulfilimines with one methyl group in the aliphatic amido moiety gave better activity than those corresponding structures with two methyl groups, so it was concluded that the conventional second

Figure 3. CoMFA results for data set 1. The molecule shown in this figure is Ia. 11059

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diamide derivatives as agricultural and horticultural insecticides. WO2001000575, 2001. (2) Katsuhira, T.; Furuya, T.; Gotoh, M.; Tohnishi, M.; Takaishi, H.; Sakata, K.; Morimoto, M.; Seo, A. Preparation of heterocyclic dicarboxylic acid diamide derivatives as agricultural and horticultural insecticides. EP 1188745, 2000. (3) Tohnishi, M.; Nakao, H.; Furuya, T.; Seo, A.; Kodama, H.; Tsubata, K.; Freudenberger, J. H.; Cordova, D.; Flexner, L.; Bellin, C. A.; Dubas, C. M.; Smith, B. K.; Hughes, K. A.; Hollingshaus, J. G.; Clark, C. E.; Benner, E. A. Flubendiamide, a novel insecticide highly active against lepidopterous insect pests. J. Pestic. Sci. 2005, 30, 354− 360. (4) Hamaguchi, H.; Hirooka, T. Insecticides affecting calcium homeostasis − flubendiamide. In Modern Crop Protection Compounds, 2nd ed.; Kr̈amer, W., Schirmer, U., Jeschke, P., Witschel, M., Eds.; Wiley-VCH Verlag: Weinheim, Germany, 2012; Vol. 3, pp 1396− 1409. (5) Seo, A.; Tohnishi, M.; Nakao, H.; Furuya, T.; Kodama, H.; Tsubata, K.; Fujioka, S.; Kodama, H.; Nishimatsu, T.; Hirooka, T. Flubendiamide, a new insecticide characterized by its novel chemistry and biology. In Pesticide Chemistry: Crop Protection, Public Health, Environmental Safety; Ohkawa, H., Miyagawa, H., Lee, P. W., Eds.; Wiley-VCH Verlag: Weinheim, Germany, 2007; pp 127−135. (6) Nakao, H.; Harayama, H.; Yamaguchi, M.; Tohnishi, M.; Morimoto, M.; Fujioka, S. Preparation of phthalamide derivatives as insecticides. WO 2002088074, 2002. (7) Harayama, H.; Tohnishi, M.; Morimoto, M.; Fujioka, S. Preparation of phthalamide derivatives as insecticides. WO 2002088075, 2002. (8) Mochizuki, K.; Inoue, S.; Hatanaka, T. Optically active phthalamide derivative, agricultural or horticultural insecticide, and method of using the same. U.S. 2008260440, 2008. (9) Tohnishi, M.; Nakao, H.; Kohno, E.; Nishida, T.; Furuya, T.; Shimizu, T.; Seo, A.; Sakata, K.; Fujioka, S.; Kanno, H. Preparation of phthalic acid diamides as agricultural and horticultural insecticides. EP 0919542, 1999. (10) Tohnishi, M.; Nakao, H.; Kohno, E.; Nishida, T.; Furuya, T.; Shimizu, T.; Seo, A.; Sakata, K.; Fujioka, S.; Kanno, H. Preparation of phthalamides as agrohorticultural insecticides. EP 1006107, 2000. (11) Tozai, M.; Morimoto, M.; Fujioka, N.; Seo, A. Preparation of phthalicdiamides and insecticides for agriculture and horticulture. JP 2001335559, 2001. (12) Wada, K.; Gomibuchi, T.; Yoneta, Y.; Otsu, Y.; Shibuya, K.; Matsuo, H.; Fischer, R. Preparation of phthalamide derivatives as insecticides. WO 2004000796, 2003. (13) Wada, K.; Gomibuchi, T.; Yoneta, Y.; Otsu, Y.; Shibuya, K.; Nakakura, N.; Fischer, R. Preparation of N1-(pyrazol-1-ymethyl)-2methylphenyl) phthalamides and related compounds as insecticides. WO 2005095351, 2005. (14) Lahm, G. P.; Selby, T. P.; Frendenberger, J. H.; Stevenson, T. M.; Myers, B. J.; Seburyamo, G.; Smith, B. K.; Flexner, L.; Clark, C. E.; Cordova, D. Insecticidal anthranilic diamides: a new class of potent ryanodine receptor activators. Bioorg. Med. Chem. Lett. 2005, 15, 4898−4906. (15) Lahm, G. P.; Cordova, D.; Barry, J. D. New and selective ryanodinereceptor activators for insect control. Bioorg. Med. Chem. 2009, 17, 4127−4133. (16) Lahm, G. P.; Stevenson, T. M.; Selby, T. P.; Freudenberger, J. H.; Cordova, D.; Flexner, L.; Bellin, C. A.; Dubas, C. M.; Smith, B. K.; Hughes, K. A.; Hollingshaus, J. G.; Clark, C. E.; Benner, E. A.; Rynaxypyr, T. M. A new insecticidal anthranilicdiamide that acts as a potent and selective ryanodine receptor activator. Bioorg. Med. Chem. Lett. 2007, 17, 6274−6279. (17) Hughes, K. A.; Lahm, G. P.; Selby, T. P.; Stevenson, T. M. Cyanoanthranilamide insecticides. WO2004067528, 2004. (18) DuPont Rynaxypyr Insect Control Technical Bulletin; http:// www2.dupont.com/Production_Agriculture/en_US/assets/ downloads/pdfs/Rynaxypyr_Tech_Bulletin.pdf.

Figure 4. CoMFA results for data set 2. The molecule shown in this figure is the (Sc, Rs) configuration of D (Figure 1).

with Sc configurations (I and II) have a better activity than Rc configurations. Finally, the red area surrounding the COCF3 group indicates that more electronegativity is favorable here. Compared with the results from data set 2, molecules with a COCF3 group in the aliphatic amide moiety give a similar conclusion. The similarity between Figures 3 and 4 indicates that the structure−activity relationship reported in a previous paper19 is also suitable for these COCF3-substitued molecules. A partial least-square analysis gives an excellent linear relationship between predicted and actual activities (R2 = 1.000), which indicates a valid CoMFA model. In summary, this is the first report of chiral N-trifluoroacetyl sulfilimines. Four series of phthalamides were designed, synthesized, and evaluated against oriental armyworm and diamondback moth for insecticidal activity. These N-trifluoroacetyl sulfilimines exhibited a sequence of activity against oriental armyworm of (Sc, Ss) ≥ (Sc, Rs) ≫ (Rc, Rs) > (Rc, Ss), whereas carbon chirality influenced the activities more strongly than sulfur. For diamondback moth, compounds If, IIa, and IIc exhibited much stronger activity than flubendiamide. CoMFA calculation indicated that stereoisomers with Sc configurations containing more electronegative groups such as COCF3 are favorable to attain their high activity. It was further concluded that the conventional second methyl group in the aliphatic amido side chain of dicarboxamide might not be a requisite in search of novel sulfiliminyl insecticides.

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AUTHOR INFORMATION

Corresponding Author

*(Z.L.) Phone: +86-22-23503732. E-mail: [email protected]. Funding

This work was supported by the Project supported by the National Basic Research Program of China (No. 2010CB126106), the National Key Technologies R&D Program (No. 2011BAE06B05), and Syngenta Postgraduate Fellowship awarded to S. Zhou. Notes

The authors declare no competing financial interest.

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REFERENCES

(1) Katsuhira, T.; Furuya, T.; Gotoh, M.; Tohnishi, M.; Sakata, K.; Morimoto, M.; Seo, A. Preparation of heterocyclic dicarboxylic acid 11060

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(19) Zhou, S.; Jia, Z. H.; Xiong, L. X.; Yan, T.; Yang, N.; Wu, G. P.; Song, H. B.; Li, Z. M. Chiral dicarboxamide scaffolds containing sulfiliminyl moiety as potential ryanodine receptor activators. J. Agric. Food Chem. 2014, 62 (27), 6269−6277. (20) Li, Z. M.; Zhou, S.; Yan, T.; Zhou, Y. Y.; Xiong, L. X.; Li, Y. Q. Preparation of chiral bisamide derivatives and geometric isomers as insecticides. CN103420884A, 2013. (21) Muller, K.; Faeh, C.; Diederich, F. Fluorine in pharmaceuticals: looking beyond intuition. Science 2007, 317, 1881−1887. (22) Dobele, M.; Wiehn, M. S.; Brase, S. Traceless solide-phase synthesis of trifluoromethylarenes. Angew. Chem., Int. Ed. 2011, 50, 11533−11535. (23) Singh, R. P.; Shreeve, J. M. Nucleophili trifluoromethylation reactions of organic compounds with (trifluoromethyl) trimethylsilane. Tetrahedron 2000, 56, 7613−7632. (24) Wiehn, M. S.; Vinogradova, E. V.; Togni, A. Electrophilic trifluoromethylation of arenes and N-heteroarenes using hypervalent iodine reagents. J. Fluorine Chem. 2010, 131, 951−957. (25) Fantasia, S.; Welch, J. M.; Togni, A. Reactivity of a hypervalent iodine trifluoromethylation reagent toward THF: ring opening and formation of trifluoromethyl ethers. J. Org. Chem. 2010, 75, 1779− 1782. (26) Zhou, S.; Yan, Tao.; Wang, B. L.; Li, Z. Design, synthesis, structure-activity relationship and insecticidal activities of trifluoromethyl-containing sulfiliminyl and sulfoximinyl phthalic acid diamide structures. Chin. J. Chem. 2014, 32 (7), 567−562. (27) García Mancheño, O.; Bistri, O.; Bolm, C. Iodine and metal-free synthesis of N-cyano sulfilimines: novel and easy access of NHsulfoximines. Org. Lett. 2007, 19, 3809−3811. (28) Sheldrick, G. M. SHELXS97 and SHELXL97; University of Göttingen, Germany, 1997. (29) Abbott, W. S. A method of computing the effectiveness of an insecticide. J. Econ. Entomol. 1925, 18, 265−267. (30) Raymond, M. Presentation d’un programme Basicd’analyse logprobit pour miero-ordinateur. Cah. ORSTOM Ser. Ent. Med. Parasitol. 1985, 23, 117−121. (31) Wu, Y. D.; Shen, J. L.; Chen, J.; Lin, X. W.; Li, A. M. Evaluation of two resistance monitoring methods in Helicoverpa armigera: topical application method and leaf dipping method. Plant Prot. 1996, 22 (5), 3−6. (32) Ma, H.; Wang, K. Y.; Xia, X. M.; Zhang, Y.; Guo, Q. L. The toxicity testing of five insecticides to different instar larvae of Spodoptera exigua. Mod. Agrochem. 2006, 5, 44−46. (33) Busivine, J. R. Recommended methods for measurement of pest resistance to pesticides. FAO Plant Production and Protection Paper 21; FAO: Rome, Italy, 1980; pp 3−13 and 119−122. (34) Sun, N. B.; Liu, X. H.; Weng, J. Q.; Tan, C. X. An unexpected product N-(3-((2-fluorobenzyl)thio)-5-methyl-4H-1,2,4-triazol-4-yl)acetimidamide: synthesis and structure analysis. J. Chem. Soc. Pak. 2013, 35, 499−502. (35) Jin, J. C.; Sun, Z. H.; Yang, M. Y.; Wu, J.; Liu, X. H. Synthesis, crystal structure, and theoretical studies of N-(4-((4-chlorobenzyl)oxy)phenyl)-4-(trifluoromethyl)pyrimidin-2-amine. J. Chem. 2013, 2013, No. 521757. (36) Liu, X. H.; Weng, J. Q.; Tan, C. X. Synthesis, crystal structure, and fungicidal activity of 5-(4-cyclopropyl-5-((3-fluorobenzyl)thio)4H-1,2,4-triazol-3-yl)-4-methyl-1,2,3-thiadiazole. J. Chem. 2013, 2013, No. 306361. (37) Liu, X. H.; Tan, C. X.; Weng, J. Q.; Liu, H. J. (E)-(4Bromobenzylidene)amino cyclopropanecarboxylate. Acta Crystallogr. E 2012, 68, O493. (38) Tan, C. X.; Weng, J. Q.; Liu, Z. X.; Liu, X. H.; Zhao, W. G. Synthesis, crystal structure, and fungicidal activity of a novel 1,2,3thiadiazole compound. Phosphorus Sulfur Silicon Relat. Elem. 2012, 187, 990−996. (39) Zhou, S.; Yan, T.; Li, Y. X.; Jia, Z. H.; Wang, B. L.; Zhao, Y.; Qiao, Y. Y.; Xiong, L. X.; Li, Y. Q.; Li, Z. M. Novel phthalamides containing sulfiliminyl moieties and derivatives as potential ryanodine receptor modulators. Org. Biomol Chem. 2014, 12 (34), 6643−6652.

(40) Liu, X. H.; Sun, Z. H.; Yang, M. Y.; Tan, C. X.; Weng, J. Q.; Zhang, Y. G.; Ma, Y. Microwave assistant one pot synthesis, crystal structure, antifungal activities and 3D-QSAR of novel 1,2,4-triazolo[4,3-9a]pyridines. Chem. Biol. Drug Des. 2014, 84, 342−347. (41) Sun, G. X.; Sun, Z. H.; Yang, M. Y.; Liu, X. H.; Ma, Y.; Wei, Y. Y. Design, synthesis, biological activities and 3D-QSAR of new N,N′diacylhydrazines containing 2,4-dichlorophenoxy moieties. Molecules 2013, 18, 14876−14891. (42) Sun, N. B.; Shi, Y. X.; Liu, X. H.; Ma, Y.; Tan, C. X.; Weng, J. Q.; Jin, J. Z.; Li, B. J. Design, synthesis, antifungal activities and 3DQSAR of new N,N′-diacylhydrazines containing 2,4-dichlorophenoxy moiety. Int. J. Mol. Sci. 2013, 14, 21741−21756. (43) Liu, X. H.; Xu, X. Y.; Tan, C. X.; Weng, J. Q.; Chen, J. Synthesis, crystal structure, herbicidal activities and 3D-QSAR study of some novel 1,2,4-triazolo[4,3-a]pyridine derivatives. Pest Manag. Sci. DOI: 10.1002/ps.3804. (44) SYBYL 6.9, Tripos Associates, St. Louis, MO, USA.

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dx.doi.org/10.1021/jf503513n | J. Agric. Food Chem. 2014, 62, 11054−11061