Supporting information

Design, synthesis, insecticidal activity and 3D‐QSR study for novel 

trifluoromethyl pyridine derivatives containing an 1,3,4‐oxadiazole 

moiety 

F.Z. Xua, Y.Y. Wanga, †, D.X. Luoa, G. Yua, S.X. Guoa, H. Fua, Y.H. Zhaob, and J. Wua‡ 

a. State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key

Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education,

Research and Development Center for Fine Chemicals, Guizhou University, Huaxi District,

Guiyang, P.R. China, 550025.

b. Institute for the Control of Agrochemicals, Ministry of Agriculture, Beijing, China. 100125.

Corresponding author; E-mail address: wujian2691@126.com, jwu6@gzu.edu.cn

‡ Co-first author for this manuscript.

†To whom correspondence should be addressed. Tel.: +86(851)88292090; fax: +86(851)

88292090. E-mails: jianwu2691@126.com, jwu6@gzu.edu.cn

1. Superimposition of compounds for the 3D-QSAR study

Fig. S1 Superimposition of compounds for the 3D‐QSAR study. (A). Common substructure; (B) result of 

superimposition   

Electronic Supplementary Material (ESI) for RSC Advances.This journal is © The Royal Society of Chemistry 2018

2. The Tables for the results of 3D-QSAR study

Table S1. Statistical parameters of CoMFA and CoMSIA models 

Statistical parameter  CoMFA  CoMSIA 

q2 a  0.742  0.614 

ONC b  5  6 

r2 c  0.975  0.92 

Standard Error of Estimate  0.044  0.084 

F values  92.362  32.793 

Fraction of field contributions d 

Steric  0.586  0.511 

Electrostatic  0.414  0.489 

Hydrophobic    ‐  0 

Hydrogen‐bond Donor  ‐  0 

Hydrogen‐bond Acceptor    ‐  0 

a Cross‐validated correlation; b Optimum number of components; 

  c Non‐cross‐validated correlation; f Field contributions. 

Table S2. Results of experimental pLC50 and predicted pLC50 

Compounds  Experimental PLC50 CoMFA  CoMSIA 

Predc.a  Res.b  Predc.a    Resb 

E1  3.058  3.014    0.046  3.054  0.004 

E2  3.16  3.173    ‐0.033  3.153  0.007 

E3  3.632  3.664    0.003  3.654  ‐0.022 

E4  3.240  3.279    ‐0.033  3.224  0.016 

E5  3.896  3.843    0.047  3.923  ‐0.027 

E6  3.573  3.565    0.011  3.586  ‐0.013 

E7*  3.615  3.493  0.122  3.809  ‐0.194 

E8*  3.731  3.729  0.022  3.79  ‐0.059 

E9*  3.82  3.847  0.047  3.861  ‐0.041 

E10  3.603  3.635    ‐0.125  3.737  ‐0.134 

E11  3.808  3.921    ‐0.114  3.745  0.063 

E12  3.836  3.803    0.092  3.811  0.025 

E13  3.975  4.003  ‐0.028  4.043  ‐0.068 

E14  3.788  3.684    0.113  3.748  0.04 

E15  3.863  3.901    0.099  3.787  0.076 

  E16*  3.768  3.797  ‐0.029  3.79  ‐0.022 

E17  3.765  3.725    ‐0.16  3.748  0.017 

E18  4.009  4.011    ‐0.002  4.010  ‐0.001 

E19  3.824  3.854    0.028  3.856  ‐0.032 

E20  3.683  3.691  0.027  3.654  0.029 

E21  3.835  3.824  0.031  3.79  0.045 

  E22*  3.634  3.683  ‐0.019  3.765  ‐0.131 

E23  3.742  3.772  0.03  3.744  ‐0.002 

E24  3.659  3.679  ‐0.07  3.755  ‐0.096 

E25  3.646  3.674    ‐0.178  3.765  ‐0.119 

  E26*  3.806  3.904  0.002  3.805  0.001 

E27#    4.106  4.055  0.051  3.855  0.251 

E28#  3.442  3.406  ‐0.184  3.47  ‐0.028 

*Sample of the test set; # Componds Predicted by the 3D‐QSAR models 

3. The 1H, 13C, 19F NMR and HR-MS spectra of the title compounds

Fig. S2 1H NMR spectra of compound E1

Fig. S3 13C NMR spectra of compound E1

Fig. S4 19F NMR spectra of compound E1

Fig. S5 HR-MS spectra of compound E1

2017120106 #105 RT: 1.02 AV: 1 NL: 8.64E7T: FTMS + p ESI Full ms [100.0000-1000.0000]

280 290 300 310 320 330 340 350 360 370

m/z

0

10

20

30

40

50

60

70

80

90

100

Rel

ativ

e A

bund

ance

326.02969C14 H8 O N3 Cl F3 = 326.03025

-1.70885 ppm

340.25894

328.02670348.01163

351.24997362.24075

284.29431 338.34109360.32315309.27826301.14056 323.25775 367.21878331.25314291.19412

Fig. S6 1H NMR spectra of compound E2

Fig. S7 13C NMR spectra of compound E2

Fig. S8 19F NMR spectra of compound E2

Fig. S9 HR-MS spectra of compound E2

2017121507 #151 RT: 1.47 AV: 1 NL: 1.47E7T: FTMS + p ESI Full ms [100.0000-1000.0000]

370.0 370.5 371.0 371.5 372.0 372.5 373.0 373.5 374.0 374.5 375.0 375.5

m/z

0

10

20

30

40

50

60

70

80

90

100

Rel

ativ

e A

bund

ance

374.00598C15 H9 O N3 Cl2 F3 = 374.00693

-2.53211 ppm

375.00980370.22757

371.22653

373.12787C15 H8 O N3 Cl2 F3 = 372.99910

345.09674 ppm

Fig. S10 1H NMR spectra of compound E3

Fig. S11 13C NMR spectra of compound E3

Fig. S12 19F NMR spectra of compound E3

Fig. S13 HR-MS spectra of compound E3

2017121508 #147 RT: 1.43 AV: 1 NL: 2.35E7T: FTMS + p ESI Full ms [100.0000-1000.0000]

370.0 370.5 371.0 371.5 372.0 372.5 373.0 373.5 374.0 374.5 375.0 375.5

m/z

0

10

20

30

40

50

60

70

80

90

100

Rel

ativ

e A

bund

ance

374.00607C15 H9 O N3 Cl2 F3 = 374.00693

-2.28732 ppm

375.00967

370.22778 371.22678 373.12759372.38257 374.13120

Fig. S14 1H NMR spectra of compound E4

Fig. S15 13C NMR spectra of compound E4

Fig. S16 19F NMR spectra of compound E4

Fig. S17 HR-MS spectra of compound E4

2017120152 #123 RT: 1.19 AV: 1 NL: 7.22E6T: FTMS + p ESI Full ms [100.0000-1000.0000]

339.0 339.5 340.0 340.5 341.0 341.5

m/z

0

10

20

30

40

50

60

70

80

90

100

Rel

ativ

e A

bund

ance

340.04596C15 H10 O N3 Cl F3 = 340.04590

0.17254 ppm

341.04938340.25949

340.76126339.34500

Fig. S18 1H NMR spectra of compound E5

Fig. S19 13C NMR spectra of compound E5

Fig. S20 19FNMR spectra of compound E5

Fig. S21 HR-MS spectra of compound E5

2017120153 #175 RT: 1.69 AV: 1 NL: 5.44E5T: FTMS + p ESI Full ms [100.0000-1000.0000]

390.0 390.5 391.0 391.5 392.0 392.5 393.0 393.5 394.0 394.5 395.0 395.5

m/z

0

10

20

30

40

50

60

70

80

90

100

Rel

ativ

e A

bund

ance

393.95306C14 H6 O N3 Cl3 F3 = 393.95231

1.92379 ppm

393.21002

394.87494

395.21527

Fig. S22 1H NMR spectra of compound E6

Fig. S23 13C NMR spectra of compound E6

Fig. S24 19F NMR spectra of compound E6

Fig. S25 HR-MS spectra of compound E6

2017120154 #135 RT: 1.31 AV: 1 NL: 2.38E7T: FTMS + p ESI Full ms [100.0000-1000.0000]

352.5 353.0 353.5 354.0 354.5 355.0 355.5 356.0

m/z

0

10

20

30

40

50

60

70

80

90

100

Rel

ativ

e A

bund

ance

354.06137C16 H12 O N3 Cl F3 = 354.06155

-0.50842 ppm

355.06497

353.26611

354.13242

352.75519353.98389

Fig. S26 1H NMR spectra of compound E7

Fig. S27 13C NMR spectra of compound E7

Fig. S28 19F NMR spectra of compound E7

Fig. S29 HR-MS spectra of compound E7

2017120155 #147 RT: 1.43 AV: 1 NL: 6.97E6T: FTMS + p ESI Full ms [100.0000-1000.0000]

352 353 354 355 356 357 358

m/z

0

10

20

30

40

50

60

70

80

90

100

Rel

ativ

e A

bund

ance

354.06128C16 H12 O N3 Cl F3 = 354.06155

-0.76699 ppm

356.05838

355.06509352.25476357.06146353.26584352.75476 355.25140 358.26953354.23856

Fig. S30 1H NMR spectra of compound E8

Fig. S31 13C NMR spectra of compound E8

Fig. S32 19F NMR spectra of compound E8

Fig. S33 HR-MS spectra of compound E8

2017120155 #147 RT: 1.43 AV: 1 NL: 6.97E6T: FTMS + p ESI Full ms [100.0000-1000.0000]

352 353 354 355 356 357 358

m/z

0

10

20

30

40

50

60

70

80

90

100

Rel

ativ

e A

bund

ance

354.06128C16 H12 O N3 Cl F3 = 354.06155

-0.76699 ppm

356.05838

355.06509352.25476357.06146353.26584352.75476 355.25140 358.26953354.23856

Fig. S34 1H NMR spectra of compound E9

Fig. S35 13C NMR spectra of compound E9

Fig. S36 19F NMR spectra of compound E9

Fig. S37 HR-MS spectra of compound E9

2017120156 #135 RT: 1.31 AV: 1 NL: 3.06E6T: FTMS + p ESI Full ms [100.0000-1000.0000]

433 434 435 436 437 438 439

m/z

0

10

20

30

40

50

60

70

80

90

100

Rel

ativ

e A

bund

ance

437.90149C14 H6 O N3 Br Cl2 F3 = 437.90179

-0.68902 ppm

437.23550

438.90472434.75717

433.28372 438.23853435.25897 435.75812 436.64069434.30240 439.24121433.74002

Fig. S38 1H NMR spectra of compound E10

Fig. S39 13C NMR spectra of compound E10

Fig. S40 19FNMR spectra of compound E10

Fig. S41 HR-MS spectra of compound E10

2017120157 #137 RT: 1.33 AV: 1 NL: 5.98E6T: FTMS + p ESI Full ms [100.0000-1000.0000]

447.0 447.5 448.0 448.5 449.0 449.5 450.0 450.5 451.0 451.5 452.0 452.5 453.0

m/z

0

10

20

30

40

50

60

70

80

90

100

Rel

ativ

e A

bund

ance

451.92648C14 H7 O N3 Cl F3 I = 451.92689

-0.90846 ppm

452.93011

449.76764447.76233 450.27020 452.77679448.26459 448.76245 450.76971

Fig. S42 1H NMR spectra of compound E11

Fig. S43 13C NMR spectra of compound E11

Fig. S44 19F NMR spectra of compound E11

Fig. S45 HR-MS spectra of compound E11

2017120158 #127 RT: 1.23 AV: 1 NL: 8.53E5T: FTMS + p ESI Full ms [100.0000-1000.0000]

400.0 400.5 401.0 401.5 402.0 402.5 403.0 403.5 404.0 404.5 405.0

m/z

0

10

20

30

40

50

60

70

80

90

100

Rel

ativ

e A

bund

ance

403.94077C14 H7 O N3 Br Cl F3 = 403.94076

0.00513 ppm

401.26208 404.94385403.73834402.37558

Fig. S46 1H NMR spectra of compound E12

Fig. S47 13C NMR spectra of compound E12

Fig. S48 19F NMR spectra of compound E12

Fig. S49 HR-MS spectra of compound E12

2017120159 #119 RT: 1.16 AV: 1 NL: 4.62E6T: FTMS + p ESI Full ms [100.0000-1000.0000]

419.5 420.0 420.5 421.0 421.5 422.0 422.5 423.0 423.5

m/z

0

10

20

30

40

50

60

70

80

90

100

Rel

ativ

e A

bund

ance

421.93088C14 H6 O N3 Br Cl F4 = 421.93134

-1.09922 ppm

419.78622

423.76077

422.93506

421.65155420.28882422.76361421.25790420.78885 423.27451422.29257

Fig. S50 1H NMR spectra of compound E13

Fig. S51 13C NMR spectra of compound E13

Fig. S52 19F NMR spectra of compound E13

Fig. S53 HR-MS spectra of compound E13

2017120160 #95 RT: 0.92 AV: 1 NL: 2.31E7T: FTMS + p ESI Full ms [100.0000-1000.0000]

341 342 343 344 345 346 347 348

m/z

0

10

20

30

40

50

60

70

80

90

100

Rel

ativ

e A

bund

ance

344.02042C14 H7 O N3 Cl F4 = 344.02083

-1.19949 ppm

346.01746

345.02405341.26254

347.02118344.22760343.20084341.76422 342.24527 348.02390345.23029

Fig. S54 1H NMR spectra of compound E14

Fig. S55 13C NMR spectra of compound E14

Fig. S56 19F NMR spectra of compound E14

Fig. S57 HR-MS spectra of compound E14

2017120161 #131 RT: 1.27 AV: 1 NL: 6.25E6T: FTMS + p ESI Full ms [100.0000-1000.0000]

400.0 400.5 401.0 401.5 402.0 402.5 403.0 403.5 404.0 404.5 405.0 405.5

m/z

0

10

20

30

40

50

60

70

80

90

100

Rel

ativ

e A

bund

ance

403.94049C14 H7 O N3 Br Cl F3 = 403.94076

-0.67482 ppm

405.80637404.94418401.26169 405.31323404.73062400.27866 403.20920402.23306

403.73874

Fig. S58 1H NMR spectra of compound E15

Fig. S59 13C NMR spectra of compound E15

Fig. S60 19F NMR spectra of compound E15

Fig. S61 HR-MS spectra of compound E15

2017120162 #151 RT: 1.47 AV: 1 NL: 1.35E6T: FTMS + p ESI Full ms [100.0000-1000.0000]

390 391 392 393 394 395

m/z

0

10

20

30

40

50

60

70

80

90

100

Rel

ativ

e A

bund

ance

393.95209C14 H6 O N3 Cl3 F3 = 393.95231

-0.55509 ppm

393.20895

391.28357

392.74756394.95560

394.21234390.73264 393.72900391.61905 392.28668 395.79291

Fig. S62 1H NMR spectra of compound E16

Fig. S63 13C NMR spectra of compound E16

Fig. S64 HR-MS spectra of compound E16

Fig. S65 1H NMR spectra of compound E17

2017122661 #123 RT: 1.19 AV: 1 NL: 5.19E6T: FTMS + p ESI Full ms [100.0000-1000.0000]

359.5 360.0 360.5 361.0 361.5

m/z

0

10

20

30

40

50

60

70

80

90

100

Rel

ativ

e A

bund

ance

359.99057C14 H7 O N3 Cl2 F3 = 359.99128

-1.96767 ppm

360.32306359.73376

360.99466360.23566361.32666

359.31482 360.73737 361.23056

Fig. S66 13C NMR spectra of compound E17

Fig. S67 19F NMR spectra of compound E17

Fig. S68 HR-MS spectra of compound E17

2017120164 #123 RT: 1.19 AV: 1 NL: 6.66E6T: FTMS + p ESI Full ms [100.0000-1000.0000]

357.0 357.5 358.0 358.5 359.0 359.5 360.0 360.5 361.0 361.5

m/z

0

10

20

30

40

50

60

70

80

90

100

Rel

ativ

e A

bund

ance

359.99078C14 H7 O N3 Cl2 F3 = 359.99128

-1.37425 ppm

359.23248360.32321

359.73380

361.32675360.99472

357.28574 358.27008 360.75638

Fig. S69 1H NMR spectra of compound E18

Fig. S70 13C NMR spectra of compound E18

Fig. S71 19F NMR spectra of compound E18

Fig. S72 HR-MS spectra of compound E18

2017120165 #95 RT: 0.92 AV: 1 NL: 4.53E7T: FTMS + p ESI Full ms [100.0000-1000.0000]

390.0 390.5 391.0 391.5 392.0 392.5 393.0 393.5 394.0 394.5 395.0 395.5 396.0

m/z

0

10

20

30

40

50

60

70

80

90

100

Rel

ativ

e A

bund

ance

394.01730C15 H7 O N3 Cl F6 = 394.01764

-0.84220 ppm

395.02087

393.20947391.28418

393.72781

394.22897 395.22607395.79385

392.74802390.73282

Fig. S73 1H NMR spectra of compound E19

Fig. S74 13C NMR spectra of compound E19

Fig. S75 19F NMR spectra of compound E19

Fig. S76 HR-MS spectra of compound E19

2017120166 #111 RT: 1.08 AV: 1 NL: 9.19E6T: FTMS + p ESI Full ms [100.0000-1000.0000]

390 391 392 393 394 395 396

m/z

0

10

20

30

40

50

60

70

80

90

100

Rel

ativ

e A

bund

ance

394.01740C15 H7 O N3 Cl F6 = 394.01764

-0.60985 ppm

396.01434

395.02112393.20935391.28394 392.74765 396.23462391.72211 395.22525394.21271390.73242

395.79288

393.72937

Fig. S77 1H NMR spectra of compound E20

Fig. S78 13C NMR spectra of compound E20

Fig. S79 19F NMR spectra of compound E20

Fig. S80 1H NMR spectra of compound E21

Fig. S81 13CNMR spectra of compound E21

Fig. S82 19F NMR spectra of compound E21

Fig. S83 HR-MS spectra of compound E21

2017121509 #127 RT: 1.24 AV: 1 NL: 8.70E6T: FTMS + p ESI Full ms [100.0000-1000.0000]

375.0 375.5 376.0 376.5 377.0 377.5 378.0 378.5 379.0 379.5

m/z

0

10

20

30

40

50

60

70

80

90

100

Rel

ativ

e A

bund

ance

377.98135C14 H6 O N3 Cl2 F4 = 377.98186

-1.33028 ppm

378.98532

378.21548376.29721 377.30109 379.21014378.62299 379.70999

Fig. S84 1H NMR spectra of compound E22

Fig. S85 13C NMR spectra of compound E22

Fig. S86 19F NMR spectra of compound E22

Fig. S87 HR-MS spectra of compound E22

2017121510 #103 RT: 1.00 AV: 1 NL: 5.58E7T: FTMS + p ESI Full ms [100.0000-1000.0000]

341.5 342.0 342.5 343.0 343.5 344.0 344.5 345.0 345.5

m/z

0

10

20

30

40

50

60

70

80

90

100

Rel

ativ

e A

bund

ance

344.02029C14 H7 O N3 Cl F4 = 344.02083

-1.55433 ppm

345.02386

341.76349 343.28403342.26517 344.22696343.84476342.74615 345.23029

Fig. S88 1H NMR spectra of compound E23

Fig. S89 13CNMR spectra of compound E23

Fig. S90 19F NMR spectra of compound E23

Fig. S91 HR-MS spectra of compound E23

2017121503 #111 RT: 1.08 AV: 1 NL: 1.26E8T: FTMS + p ESI Full ms [100.0000-1000.0000]

391.0 391.5 392.0 392.5 393.0 393.5 394.0 394.5 395.0 395.5 396.0

m/z

0

10

20

30

40

50

60

70

80

90

100

Rel

ativ

e A

bund

ance

394.01685C15 H7 O N3 Cl F6 = 394.01764

-2.00399 ppm

395.02032

391.28375 393.29721 394.40359393.80685

392.28720 395.40717391.72137 392.72086

Fig. S92 1H NMR spectra of compound E24

Fig. S93 13C NMR spectra of compound E24

Fig. S94 19F NMR spectra of compound E24

Fig. S95 HR-MS spectra of compound E24

2017120171 #133 RT: 1.29 AV: 1 NL: 4.62E6T: FTMS + p ESI Full ms [100.0000-1000.0000]

448.0 448.5 449.0 449.5 450.0 450.5 451.0 451.5 452.0 452.5 453.0

m/z

0

10

20

30

40

50

60

70

80

90

100

Rel

ativ

e A

bund

ance

451.92661C14 H7 O N3 Cl F3 I = 451.92689

-0.63835 ppm

452.92993449.76852 450.27072448.26550 452.77762450.77103449.26346 451.74231

452.25742

Fig. S96 1H NMR spectra of compound E25

Fig. S97 13C NMR spectra of compound E25

Fig. S98 19F NMR spectra of compound E25

Fig. S99 HR-MS spectra of compound E25

2017121511 #133 RT: 1.30 AV: 1 NL: 7.38E6T: FTMS + p ESI Full ms [100.0000-1000.0000]

448.0 448.5 449.0 449.5 450.0 450.5 451.0 451.5 452.0 452.5 453.0

m/z

0

10

20

30

40

50

60

70

80

90

100

Rel

ativ

e A

bund

ance

451.92636C14 H7 O N3 Cl F3 I = 451.92689

-1.17857 ppm

451.09946

452.93008452.10272

451.30325448.26477 452.77621449.26376 453.24210448.76263 450.27094

Fig. S100 1H NMR spectra of compound E26

Fig. S101 13C NMR spectra of compound E26

Fig. S102 19F NMR spectra of compound E26

Fig. S103 HR-MS spectra of compound E26

2017120173 #119 RT: 1.16 AV: 1 NL: 1.08E7T: FTMS + p ESI Full ms [100.0000-1000.0000]

367.0 367.5 368.0 368.5 369.0 369.5 370.0

m/z

0

10

20

30

40

50

60

70

80

90

100

Rel

ativ

e A

bund

ance

369.07220C16 H13 O N4 Cl F3 = 369.07245

-0.66464 ppm

367.21884 370.07599

367.72055 368.21994367.05692 368.72073 369.23978

Fig. S104 1H NMR spectra of compound E27

Fig. S105 13C NMR spectra of compound E27

Fig. S106 19F NMR spectra of compound E27

Fig. S107 HR-MS spectra of compound E27

2017122606 #87 RT: 0.87 AV: 1 NL: 9.17E6T: FTMS + p ESI Full ms [100.0000-1000.0000]

355.0 355.5 356.0 356.5 357.0 357.5 358.0 358.5 359.0 359.5 360.0

m/z

0

10

20

30

40

50

60

70

80

90

100

Rel

ativ

e A

bund

ance

358.03613C15 H9 O N3 Cl F4 = 358.03648

-0.96682 ppm

359.03976

359.23578355.28418 358.36807 359.73471

Fig. S108 1H NMR spectra of compound E28

Fig. S109 13C NMR spectra of compound E28

Fig. S110 19FNMR spectra of compound E28

Fig. S111 HR-MS spectra of compound E28

2017120163 #139 RT: 1.35 AV: 1 NL: 1.46E7T: FTMS + p ESI Full ms [100.0000-1000.0000]

390.0 390.5 391.0 391.5 392.0 392.5 393.0 393.5 394.0 394.5 395.0 395.5

m/z

0

10

20

30

40

50

60

70

80

90

100

Rel

ativ

e A

bund

ance

393.95184C14 H6 O N3 Cl3 F3 = 393.95231

-1.17481 ppm

394.95569

393.20932391.28339 395.79315394.21289392.74799391.72159

393.72812

390.73239 395.11008

394.75348