Indian Patents. 270640:BENZAMIDE COMPOUNDS AND APPLICATIONS THEREOF

Title of Invention	BENZAMIDE COMPOUNDS AND APPLICATIONS THEREOF
Abstract	This invention disclosed a novel kind of benzamide compounds as represented by formula I, and the intermediates to prepare the compounds of formula I as represented by formula II, and their use thereof: I II Every substituent is defined in the text. The formula I compounds possess outstanding fungicidal or insecticidal activity and can be used to control insects or diseases.

Full Text	FORM 2 THE PATENTS ACT 1970 (39 of 1970) & The Patents Rules, 2003 COMPLETE SPECIFICATION (See section 10 and rule 13) 1. ' BENZAMIDE COMPOUNDS AND APPLICATIONS THEREOF ' 2. 1. (A) SINOCHEM CORPORATION (B) A Company incorporated under the laws of China. (C) 6-12F Central Tower, Chemsunny World Trade Center, 28 Fuxingmennei Dajie, Beijing 100045 China 2. (A) SHENYANG RESEARCH INSTITUTE OF CHEMICAL INDUSTRY_CO., LTD (B) A Company incorporated under the laws of China. (C) 8 Shenliaodong Road, Tiexi District, Shenyang Liaoning 110021 China The following specification particularly describes the invention and the manner in which it is to be performed. BENZAMIDE COMPOUNDS AND APPLICATIONS THEREOF FIELD OF THE INVENTION This invention belongs to the field of insecticide and fungicide, relates to benzamide compounds and applications thereof. BACKGROUND OF THE INVENTION The search for the novel and improved fungicidal and insecticidal compounds and compositions is continually needed because of the emergence and development of the fungi and insect resistance to the existing fungicides and insecticides after a period of applications. Some insecticidal benzamides were disclosed in WO03/015518A1, which are highly effective against fall armyworm (Spodoptera frugiperda) at 50 ppm. Neither the preparation of cyanoalkyl substituted benzamides, nor their fungicidal or insecticidal activities according to the present invention are described in any literature. SUMMARY OF THE INVENTION The purpose of this invention is to provide a kind of novel benzamides, and their applications as fungicides or insecticides. The technical embodiment of this invention is as follows: The present invention provides a kind of benzamides as represented by formula I: I Wherein: R1 is H or C1-C6 alkyl; R2 is H or C1-C6 alkyl; R3 is C1-C6 alkyl or C3-C6 cycloalkyl, the hydrogen group on the all substituents can also be further substituted by the following groups: halogen, NO2, C1-C3 alkoxy, phenoxy, C1-C3 alkylthio, C1-C3 alkylsulfinyl or C1-C3 alkylsulfonyl; Or R2 and R3 form C3-C6 cycloalkyl together with their connected carbon; R4 is H, halogen or CN; R5 is halogen or C1-C3 alkyl; R6 is halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy or C1-C3 haloalkoxy; R7 is H, halogen, CN, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 alkylthio, C1-C3 alkylsulfinyl or C1-C3 alkylsulfonyl; R8 is halogen, CN, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy or C1-C3 alkythio; X is CH, CF, CCl or N. The preferred compounds of the formula I in this invention are: R1 is H; R2 is H or C1-C3 alkyl; R3 is C1-C3 alkyl; Or R2 and R3 form C3-C6 cycloalkyl together with their connected carbon; R4 is H, halogen or CN; R5 is halogen or C1-C3 alkyl; R6 is halogen or C1-C3 haloalkyl; R7 is H, halogen, CN or C1-C3 haloalkyl; R8 is halogen; X is CH, CF, CCl or N. The more preferred compounds of the formula I in this invention are: R1 is H; R2 is H or methyl; R3 is methyl; R4 is Cl, Br, I, or CN; R5 is Cl, Br or methyl; R6 is Cl, Br or CF3; R7 is H, Cl or CF3; R8 is Cl; X is CH, CF, CCl or N. This invention further relates to the compounds of formula II for the preparation of the compounds of formula I, which are not described in any literature. II Wherein: R1 is H or C1-C6 alkyl; R2 is H or C1-C6 alkyl; R3 is C1-C6 alkyl or C3-C6 cycloalkyl, the hydrogen group on the all substituents can also be further substituted by the following groups: halogen, NO2, C1-C3 alkoxy, phenoxy, C1-C3 alkylthio, C1-C3 alkylsulfinyl or C1-C3 alkylsulfonyl; Or R2 and R3 form C3-C6 cycloalkyl together with their connected carbon; R4 is H, halogen or CN; R5 is halogen or C1-C3 alkyl; In above definations of the compounds of formula I, the term “alkyl” indicates straight or branched alkyl such as methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, n-pentyl, i-pentyl, n-hexyl, etc.. “Cycloalkyl” includes, for example, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl, etc.. “Haloalkyl” denotes that alkyl is partially or fully substituted with halogen atoms. “Alkoxy” is that the end of alkyl is oxygen, such as methoxy, ethoxy, n-propyloxy, i-propyloxy, t-butoxy, etc.. “Haloalykoxy” is that the end of the alkyl substituted with one or more halogen atoms is oxygen. “Alkylthio” is that the end of alkyl is the sulfur, such as methylthio, ethylthio etc.. “Alksulfinyl” is that the end of alkyl is the sulfinyl group (SO-), such as methsulfinyl. “Alksulfonyl” is that the end of alkyl is the sulfonyl group (SO2-), such as methsulfonyl. “Halogen” includes fluorine, chlorine, bromine, and iodine. The compounds of the formula I in the present invention can be prepared by the following processes, and the substituents in the reaction formula are same as above definitions: II III I The compounds of formula II and III in an appropriate solvent are reacted to yield the compounds of formula I at a certain temperature between -10 ºC and the boiling point of the solvent for 30 minutes to 48 hours. The appropriate solvent was chosen from dichloromethane, chloroform, carbon tetrachloride, hexane, benzene, toluene, ethyl acetate, acetonitrile, tetrahydrofuran, dioxane, DMF or DMSO etc.. The appropriate base is advantageous to the reaction. The appropriate base was chosen from organic base such as sodium methoxide, sodium tert-butoxide, potassium tert-butoxide, triethylamine, N, N-dimethylaniline, pyridine etc. or inorganic base such as sodium carbonate, potassium carbonate, sodium bicarbonate, sodium hydroxide, or potassium hydroxide etc. The compounds of the formula II can be prepared by the following processes: IV II The nitro compounds IV reacted with reducing agents such as iron, zinc or hydrogen etc. (according to the method described in EPA0083055A2) in an appropriate solvent to obtain the compounds of formula II at a certain temperature between -10 ºC and the boiling point of the solvent for 30 minutes to 48 hours. The appropriate solvents include water, acetic acid, acetone, dichloromethane, chloroform, carbon tetrachloride, hexane, benzene, toluene, ethyl acetate, ethanol, DMF, THF, ioxane or the mixture solvent of above two or three solvents etc.. The compounds of formula II (wherein R4 is H) reacted with halogenation reagent such as halogen, N-chlorosuccinimide etc., in an appropriate solvent to obtain the compounds of formula II (wherein R4 is halogen) at a certain temperature between -10 ºC and the boiling point of the solvent for 30 minutes to 48 hours. The appropriate solvents include dichloromethane, chloroform, carbon tetrachloride, DMF, THF, dioxane or DMSO etc.. The halogens include iodine, bromine or chlorine. The compounds of formula II (wherein R4 is halogen) reacted with cyanation reagent in the appropriate solvent to obtain the compounds of formula II (wherein R4 is CN) at a certain temperature between -10 ºC and the boiling point of the solvent for 30 minutes to 48 hours. The cyanation reagents include sodium cyanide, potassium cyanide or cuprous cyanide. The appropriate solvents include DMF, THF, dioxane or dimethylsulfoxide etc.. The halogens include iodine, bromine or chlorine. The compounds of the formula IV can be prepared by the following processes: V VI IV The benzoyl chloride V (commercially available, prepared according to the following literature: March J, Advanced Organic Chemistry, 4th Ed, John Wiley & sons, 1992) reacted with aminocyanoalkane VI (commercially available, prepared according to the following literature: J. Peptide Res. 56, 2000, 283-297) in an appropriate solvent to obtain the compounds of formula IV at a certain temperature between -10 ºC and the boiling point of the solvent for 30 minutes to 48 hours. The appropriate solvents include chloroform, dichloromethane, carbon tetrachloride, hexane, benzene, toluene, ethyl acetate, DMF, THF or dioxane etc.. The appropriate base, for example triethylamine, pyridine, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate or sodium bicarbonate etc. is advantageous to the reaction. The compounds of formula III (pyrazolcarbonyl chloride and the corresponding acid) are prepared according to the following literature: Bioorganic & Medicinal Chemistry Letters, 2005, 15, 4898-4906. The structures and their physical properties of some representative compounds of formula I are shown in Table 1. Table 1: The structures and their physical properties of some representative compounds of formula I Compound R2 R3 R4 R5 R6 R7 R8 X Appearance (m.p.(?)) 1.1a H CH3 H CH3 Br H Cl N white solid (146-150) 1.1 H CH3 Cl CH3 Br H Cl N white solid (205-207) 1.2 H CH3 Cl CH3 Cl H Cl N white solid (197-199) 1.3 H CH3 Br CH3 Cl H Cl N white solid (138-140) 1.4 H CH3 Br CH3 Br H Cl N white solid (208-209) 1.5 H CH3 I CH3 Cl H Cl N white solid (135-137) 1.6 H CH3 Cl Cl Cl H Cl N white solid (165-168) 1.7 H CH3 Br Cl Cl H Cl N white solid (167-170) 1.8 H CH3 I Cl Cl H Cl N white solid (168-173) 1.9 H CH3 Cl Cl Br H Cl N white solid (153-156) 1.10 H CH3 Br Cl Br H Cl N white solid (153-157) 1.11 H CH3 I Cl Br H Cl N white solid (154-158) 1.12 H CH3 CN Cl Br H Cl N 1.13 H CH3 CN CH3 Br H Cl N white solid (210-213) 1.14a CH3 CH3 H CH3 Br H Cl N white solid (248-253) 1.14 CH3 CH3 Cl CH3 Br H Cl N white solid (191-194) 1.15 CH3 CH3 Cl CH3 Cl H Cl N white solid (213-216) 1.16 CH3 CH3 Br CH3 Br H Cl N white solid (175-177) 1.17 CH3 CH3 Cl Cl Cl H Cl N white solid (149-151) 1.18 CH3 CH3 Cl Cl Br H Cl N white solid (254-256) 1.19 CH3 CH3 Cl CH3 Cl H Cl CH white solid (252-254) 1.20 CH3 CH3 Br CH3 Cl H Cl CH white solid (248-250) 1.21 CH3 CH3 Br Br Cl H Cl CH white solid (177-180) 1.22 CH3 CH3 CN Cl Br H Cl N 1.23 CH3 CH3 CN CH3 Br H Cl N white solid (140-142) 1.24 CH3 CH3 Cl Cl CF3 H Cl CH white solid (246-248) 1.25a i-C3H7 CH3 H CH3 Br H Cl N white solid (186-188) 1.25 i-C3H7 CH3 Cl CH3 Br H Cl N white solid (204-208) 1.26 i-C3H7 CH3 Cl CH3 Cl H Cl N oil 1.27 i-C3H7 CH3 Cl CH3 Br H Cl CH white solid (120-125) 1.28 CH2 CH2 CH2 CH2 Cl CH3 Cl H Cl N white solid (165-167) 1.29 CH2 CH2 CH2 CH2 Cl CH3 Br H Cl N white solid (252-256) 1.30 CH2 CH2 CH2 CH2 CH2 Cl CH3 Cl H Cl N white solid (226-228) 1.31 CH2 CH2 CH2 CH2 CH2 Cl CH3 Br H Cl N white solid (225-227) Table 2: The structures and their physical properties of some representative compounds of formula II Compound R2 R3 R4 R5 Appearance (m.p.(?)) 2.1 H CH3 H CH3 white solid (105-106) 2.2 H CH3 Cl CH3 white solid (139-140) 2.3 H CH3 Br CH3 wax 2.4 H CH3 I CH3 wax 2.5 H CH3 H Cl 2.6 H CH3 Cl Cl 2.7 H CH3 Br Cl 2.8 H CH3 I Cl 2.9 H CH3 CN Cl 2.10 H CH3 CN CH3 2.11 CH3 CH3 H CH3 white solid (173-174) 2.12 CH3 CH3 Cl CH3 white solid (199-201) 2.13 CH3 CH3 Br CH3 2.14 CH3 CH3 I CH3 wax 2.15 CH3 CH3 CN Cl 2.16 CH3 CH3 CN CH3 2.17 i-C3H7 CH3 H CH3 wax 2.18 i-C3H7 CH3 Cl CH3 white solid (125-127) 2.19 i-C3H7 CH3 H H white solid (129-130) 2.20 i-C3H7 CH3 Cl Cl 2.21 CH2 CH2CH2CH2 H CH3 white solid (142-143) 2.22 CH2 CH2CH2CH2 Cl CH3 wax 2.23 CH2 CH2CH2CH2CH2 H CH3 white solid (136-138) 2.24 CH2 CH2CH2CH2CH2 Cl CH3 white solid (131-133) Compounds 1H NMR (300MHz, CDCl3) data: Compound 1.1a: 9.855 (s, 1H), 8.476-8.454 (q, 1H), 7.879-7.847 (q, 1H), 7.407-7.316 (m, 3H), 7.243-7.169 (m, 1H), 7.036 (s, 1H), 7.626-7.635 (d, 1H), 4.973-4.924 (m, 1H), 2.205 (s, 3H), 1.576-1.552 (d, 3H). Compound 1.1: 9.663 (s, 1H), 8.463-8.443 (d, 1H), 7.878-7.845 (d, 1H), 7.402-7.359 (m, 1H), 7.280-7.241 (m, 2H), 7.070 (s, 1H), 6.716-6.692 (d, 1H), 4.958-4.908 (m, 1H), 2.175 (s, 3H), 1.589-1.564 (d, 3H). Compound 1.2: 9.654 (s, 1H), 8.470-8.448 (d, 1H), 7.884-7.853 (d, 1H), 7.410-7.368 (m, 1H), 7.275-7.252 (m, 2H), 6.973 (s, 1H), 6.584-6.558 (d, 1H), 4.986-4.937 (m, 1H), 2.195 (s, 3H), 1.603-1.593 (d, 3H). Compound 1.3: 9.627 (s, 1H), 8.445-8.424 (d, 1H), 7.870-7.837 (d, 1H), 7.408-7.343 (m, 3H), 6.992 (s, 1H), 6.830-6.804 (d, 1H), 4.919-4.871 (m, 1H), 2.151 (s, 3H), 1.556-1.532 (d, 3H). Compound 1.4: 9.613 (s, 1H), 8.450-8.428 (d, 1H), 7.870-7.832(d, 1H), 7.413-7.345 (m, 3H), 7.069 (s, 1H), 6.755-6.731 (d, 1H), 4.929-4.880 (m, 1H), 2.157 (s, 3H), 1.564-1.532 (d, 3H). Compound 1.5: 9.632 (s, 1H), 8.463-8.441 (d, 1H), 7.878-7.847(d, 1H), 7.696-7.597 (m, 2H), 7.402-7.359(m, 1H), 6.948 (s, 1H), 6.443 (s, 1H), 4.996-4.945 (m, 1H), 2.174 (s, 3H), 1.633-1.581 (d, 3H). Compound 1.6: 8.856 (s, 1H), 8.483-8.461 (d, 1H), 7.958-7.927(d, 1H), 7.548-7.541 (m, 1H), 7.390-7.382(m, 2H), 6.971 (s, 1H), 6.485-6.443 (d, 1H), 4.956-4.905 (m, 1H), 1.560 (s, 3H). Compound 1.7: 8.867 (s, 1H), 8.467-8.458 (d, 1H), 7.928-7.907(d, 1H), 7.688-7.675 (m, 1H), 7.527-7.520(m, 1H), 7.428-7.400 (m, 1H), 6.971 (s, 1H), 6.483-6.254(m, 1H), 4.965-4.896 (m, 1H), 1.556 (s, 3H). Compound 1.8: 8.957 (s, 1H), 8.453-8.448 (d, 1H), 7.904-7.871(d, 1H), 7.832 (s, 1H), 7.663 (s,1H), 7.415-7.396 (m, 1H), 6.992 (s, 1H), 6.455 (s, 1H), 4.955-4.932 (m, 1H), 1.563 (s, 3H). Compound 1.9: 8.875 (s, 1H), 8.465-8.318 (d, 1H), 7.923-7.895 (m, 1H), 7.556 (s, 1H), 7.394-7.376 (m, 2H), 7.056 (s, 1H), 6.523 (s, 1H), 4.958-4.939 (m, 1H), 1.571 (s, 3H). Compound 1.10: 9.141 (s, 1H), 8.450-8.434 (d, 1H), 7.881-7.855 (d, 1H), 7.543-7.536 (d, 1H), 7.420-7.353 (m, 2H), 7.119 (s, 1H), 6.817-6.791 (d, 1H), 4.885-4.837 (m, 1H), 1.510-1.487 (d, 3H). Compound 1.11: 8.978 (s, 1H), 8.489-8.464 (d, 1H), 7.923-7.845 (m, 2H), 7.673 (s, 1H), 7.425-7.386 (m, 1H), 7.069 (s, 1H), 6.493 (s, 1H), 4.956-4.913 (m, 1H), 1.569-1.548 (d, 3H). Compound 1.13: 10.346 (s, 1H), 8.556-8.452 (d, 1H), 7.866-7.834 (m, 1H), 7.749-7.746 (m, 1H), 7.636 (m, 1H), 7.407-7.380 (m, 1H), 7.267 (br, 1H), 7.047 (s, 1H), 4.970 (m, 1H), 2.262 (s, 3H), 1.627-1.614 (d, 3H). Compound 1.14a: 9.876 (s, 1H), 8.459-8.445 (d, 1H), 7.863-7.837 (d, 1H), 7.397-7.371 (m, 3H), 7.267-7.230 (m, 1H), 7.155 (s, 1H), 6.427 (s, 1H), 2.206 (s, 3H), 1.620 (s, 6H). Compound 1.14: 9.699 (s, 1H), 8.435-8.414 (d, 1H), 7.860-7.829 (d, 1H), 7.387-7.345 (m, 2H), 7.311 (s, 1H), 7.192-7.139 (m, 1H), 6.591 (s, 1H), 2.161 (s, 3H), 1.675 (s, 6H). Compound 1.15: 9.666 (s, 1H), 8.436-8.421 (d, 1H), 7.866-7.833 (d, 1H), 7.392-7.349 (m, 1H), 7.256-7.164 (m, 3H), 6.438 (s, 1H), 2.171 (s, 3H), 1.680 (s, 6H)?. Compound 1.16: 9.722 (s, 1H), 8.428-8.407 (d, 1H), 7.855-7.822 (d, 1H), 7.379-7.324 (m, 3H), 7.264 (s, 1H), 6.651 (s, 1H), 2.130 (s, 3H), 1.649 (s, 6H). Compound 1.17(CDCl+DMSO): 10.152 (s, 1H), 8.375-8.355 (d, 1H), 8.210 (s, 1H), 7.799-7.767 (d, 1H), 7.451-7.409 (m, 1H), 7.346-7.304 (m, 2H), 7.217 (s, 1H), 1.550 (s, 6H). Compound 1.18: 9.469 (s, 1H), 8.512-8.493 (d, 1H), 7.938-7.906 (d, 1H), 7.434-7.370 (m, 2H), 7.034-7.297 (d, 1H), 7.239-7.232 (d, 1H), 7.214 (s, 1H), 1.735 (s, 6H). Compound 1.19: 9.424 (s, 1H), 7.517-7.486 (m, 1H), 7.425-7.326 (m, 3H), 7.109-7.101 (d, 2H), 7.040 (s, 1H), 6.713 (s, 1H), 2.051 (s, 3H), 1.678 (s, 6H). Compound 1.20: 9.459 (s, 1H), 7.519-7.487 (m, 1H), 7.435-7.273 (m, 5H), 7.051 (s, 1H), 6.602 (s, 1H), 2.083 (s, 3H), 1.688 (s, 6H). Compound 1.21:9.011 (s, 1H), 7.528-7.497 (m, 1H), 7.388-7.271 (m, 5H), 7.167 (s, 1H), 7.025 (s, 1H), 2.175 (s, 3H), 1.621 (s, 6H). Compound 1.24: 8.415 (br s, 1H), 8.234 (d, 1H), 7.915 (d, 1H), 7.518-7.310 (m, 5H), 7.310 (br s, 1H), 1.646 (s, 6H). Compound 1.25a: 8.497-8.476 (q, 1H), 8.173-8.141 (q, 1H), 7.621-7.579 (q, 1H), 7. 405-7.390 (m, 3H), 7.281 (s, 1H), 2.192-2.094 (m, 4H), 1.402 (s, 3H), 1.027-1.004 (d, 3H), 0.884-0.863 (d, 3H). Compound 1.25: 8.494-8.482 (d, 1H), 8.175-8.149 (d, 1H), 7.627-7.585 (m, 1H), 7.528 (s, 1H), 7.392 (s, 1H), 7.316 (s, 1H), 2.260-2.193 (m, 4H), 1.410 (s, 3H), 1.024-1.002 (d, 3H), 0.877-0.858 (d, 3H). Compound 1.26: 9.784 (s, 1H), 8.441-8.421 (q, 1H), 7.862-7.831 (q, 1H), 7.404-7.353 (m, 3H), 7.216 (s, 1H), 6.396 (s, 1H), 2.271-2.188 (m, 1H), 2.166 (s, 3H), 1.562 (s, 3H), 1.110-1.087 (d, 3H), 1.019-0.996 (d, 3H). Compound 1.27: 9.555 (s, 1H), 7.501-7.350 (m, 4H), 7.282-7.274 (m, 1H), 7.230-7.222 (d, 1H), 7.178 (s, 1H), 7.150-7.142 (d, 1H), 2.148-2.109 (m, 4H), 1.601 (s, 3H), 1.150-1.128 (d, 3H), 1.048-1.027 (d, 3H). Compound 1.28: 9.688 (s, 1H), 8.446-8.425 (m, 1H), 7.865-7.832 (m, 1H), 7.389-7.346 (m, 1H), 7.234-7.228 (m, 1H), 7.181-7.163 (m, 2H), 6.541 (s, 1H), 2.458-2.414 (m, 2H), 2.169 (s, 3H), 2.045-1.977 (m, 2H), 1.878-1.748 (m, 4H). Compound 1.29 (DMSO): 10.209 (s, 1H), 8.615 (s, 1H), 8.454-8.434 (m, 1H), 7.927-7.895 (m, 1H), 7.667 (s, 1H), 7.478-7.436 (m, 1H), 7.386-7.378 (d, 1H), 7.320 (s, 1H), 2.310-2.102 (m, 7H), 1.816-1.719 (m, 4H). Compound 1.30: 9.725 (s, 1H), 8.435-8.420 (d, 1H), 7.863-7.831 (m, 1H), 7.389-7.346 (m, 1H), 7.260-7.150 (m, 3H), 6.471 (s, 1H), 2.400-2.318 (m, 2H), 2.164 (s, 3H), 1.706-1.452 (m, 8H). Compound 1.31: 9.692 (s, 1H), 8.446-8.432 (d, 1H), 7.865-7.834 (m, 1H), 7.394-7.351 (m, 1H), 7.260-7.250 (m, 2H), 7.184 (s, 1H), 6.326 (s, 1H), 2.401-2.356 (m, 2H), 2.170 (s, 3H), 1.725-1.564 (m, 8H). Compound 2.3: 7.327-7.319 (d, 1H), 7.275-7.271 (d, 1H), 6.251-6.227 (d, 1H), 5.049-4.999 (m, 1H), 2.148 (s, 3H), 1.685-1.660 (m, 3H). Compound 2.4: 7.483-7.476 (d, 1H), 7.431-7.426 (d, 1H), 6.231-6.214 (d, 1H), 5.048-4.999 (m, 1H), 2.125 (s, 3H), 1.685-1.651 (m, 3H). Compound 2.14: 7.429-7.423 (d, 1H), 7.381-7.379 (d, 1H), 6.145 (s, 1H), 2.097 (s, 3H), 1.809 (s, 6H). Compound 2.22: 7.132-7.126 (d, 1H), 7.028 (d, 1H), 6.492 (s, 1H), 5.389 (s, 2H), 2.499-2.434 (m, 2H), 2.222-2.144 (m, 2H), 1.907-1.876 (m,4H). The hydrogen atom in organic molecular can be replaced by methyl or other alkyl to improve the organic molecular’s liposolubility. The liposolubility is closely related to the transportation of organic molecules in insects, plants and other biological organisms. The suitable transportation of bioactive molecules plays an important role in the biological efficacy. The suitable transportation property of molecules is unpredictable, so it only can be obtained through extensively creative investigation. The alkyl substituted acetonitrile benzamide compounds as shown in formula I in this invention possess surprisingly high insecticidal activity and fungicidal activity compared with known acetonitrile benzamide compounds. So, this invention also provides the use of the formula I compounds for protecting plant from insects and disease. Another embodiment of this invention includes the fungicidal or insecticidal compositions, in which the compounds of formulas I are active ingredients. The weight percentage of active ingredient(s) in the compositions is from 1% to 99%. There are also carriers acceptable in agriculture, forestry or public health in these compositions. The compositions of the present invention can be used in the form of various formulations. Usually, the compounds of formula I, the active ingredient, is diluted with an inert liquid or solid carrier to make a formulation such as a wettable powder or an emulsifiable concentrate etc., so that it can be easily dispersed as a fungicide or an insecticide. Therefore, in these compositions, at least a liquid or solid carrier is added, and usually suitable surfactant(s) can be added when needed. Still also provided by this invention is the application method of controlling insects, which is to apply the compositions of the present invention to the growing loci of the insects as mentioned above. The suitably effective dosage of the compounds of the present invention is usually within a range of 10 g/ha to 1000 kg/ha, preferably from 20 g/ha to 500 g/ha. Also provided by this invention is the application method of controlling diseases, which is to apply the compositions of the present invention to the growing loci of the diseases as above mentioned. The suitably effective dosage of the compounds of the present invention is usually within a range of from 100 g/ha to 2000 g/ha, preferably from 200 g/ha to 1000 g/ha. For some applications, one or more other fungicides, insecticides, herbicides, plant growth regulators, or fertilizer can be added into the fungicidal or insecticidal compositions of the present invention to make additional merits and effects. It shall be noted that variations and changes are permitted within the claimed scopes in the present invention. DESCRIPTION OF THE INVENTION IN DETAIL The following synthesis examples and results of biological tests are used to further illustrate the present invention, but not to limit it. SYNTHSIS EXAMPLES EXAMPLE 1: SYNTHSIS OF COMPOUND 1.2 (1) Synthesis of 2-aminopropanenitrile: To a 500 mL flask sodium cyanide (4.95 g, 100 mmol) and ammonia hydrate (60 mL) were added. After sodium cyanide was solved completely, acetaldehyde (11.00 g, 100 mmol) and ammonium chloride (5.38 g, 100 mmol) were added. The reaction mixture was stirred for 48 hours at room temperature. Then dichloromethane was added to extract for 3 times (50 mL, 10 mL, 10 mL). The combined organic layers were dried over anhydrous magnesium sulfate and concentrated under vacuum to give the product (2.57 g) as a light green oil in 32% yield. (2) Synthesis of 3-methyl-2-nitrobenzoyl chloride: To a 500 mL flask 3-methyl-2-nitrobenzoic acid (20.0g, 110 mmol), 100 mL dichloromethane and oxalyl dichloride (21.0g, 165 mmol) were added. After five drops of N, N-dimethyl formamide were added, a large number of gas was released. After stirring for 8 hours at room temperature, the reaction mixture was concentrated under vacuum. Then 100 mL toluene was added, and the reaction mixture was concentrated again to give the product (22g) as a white solid in 100% yield. (3) Synthesis of N-(1-cyanoethyl)-3-methyl-2-nitrobenzamide: To a 500 mL flask 3-methyl-2-nitrobenzoyl chloride (21 g, 105 mmol), 200 mL dichloromethane and 2-aminopropanenitrile (7.0 g, 100 mmol) were added sequentially. To the mixture triethylamine (12.0 g, 120 mmol) was added dropwise and the reaction mixture was stirred for 3 hours at room temperature. Then the mixture was poured into 200 mL water and extracted with ethyl acetate (3×100 mL). The combined organic layers were washed with saturated sodium carbonate solution and brine, dried over anhydrous magnesium sulfate and concentrated to give 21.5 g dark brown oil. After separation through silica gel column chromatography (fluent: ethyl acetate/petroleum ether=1:1), 18.5 g orange solid was gained in 75% yield. 1H NMR (300MHz, CDCl3+CD3OD): 9.025-9.001 (d, 1H), 7.520-7.439 (m, 3H), 5.044-4.972 (m, 1H), 2.409 (s, 3H), 1.632-1.608 (d, 3H). (4) Synthesis of 2-amino-N-(1-cyanoethyl)-3-methylbenzamide (Compound 2.1): To a 250 mL flask N-(1-cyanoethyl)-3-methyl-2-nitrobenzamide (4.0 g, 17.2 mmol), tetrahydrofuran (40 mL), water (40 mL) and zinc powder (5.6 g, 86 mmol) were added sequentially. Concentrated hydrochloric acid (5.2 g, 51.6 mmol) was added dropwise to the mixture over the period of 30 minutes at room temperature. The reaction temperature was controlled under 30?. The reaction mixture was continued to react for 3 hours at room temperature. The insoluble substances were removed by filtration. The filtrate was extracted with ethyl acetate (2×100 mL). The combined organic extracts were washed with water, saturated sodium carbonate solution and brine, dried over anhydrous magnesium sulfate and concentrated to give the product (2.8 g) as a light yellow solid in 80% yield. 1H NMR (300MHz, CDCl3): 7.246-7.220 (d, 1H), 7.160-7.137 (d, 1H), 6.667-6.641 (d, 1H), 6.591-6.541 (t, 1H), 5.659 (s, 2H), 5.048-4.997 (m, 1H), 2.144 (s, 3H), 1.633-1.608 (d, 3H). (5) Synthesis of 2-amino-5-chloro-N-(1-cyanoethyl)-3-methylbenzamide (Compound 2.2): To a 50 mL flask 2-amino-N-(1-cyanoethyl)-3-methylbenzamide (1.8 g, 8.9 mmol) N-chloro succinimide (referred to as: NCS) (1.2 g, 8.9mmol) and dimethylformamide (20 mL) were added sequentially. The reaction mixture was stirred for 30 minutes at 100-110?. After being cooled down to room temperature, the reaction mixture was poured into 100 mL water and extracted with ethyl acetate (2×100 mL).The organic extracts were washed with water, brine, and dried over anhydrous magnesium sulfate, concentrated to give the product (1.8 g) as light yellow solid in 86% yeild. The HPLC analysis showed that there were no significant impurities . 1H NMR (300MHz, CDCl3): 7.535 (s, 1H), 7.331-7.324 (d, 1H), 7.104-7.102 (d, 1H), 5.040-5.016 (m, 1H), 2.131 (s, 3H), 1.671-1.647 (d, 3H). (6) Synthesis of 3-chloro-2-hydrazinylpyridine: To a 1000 mL flask 2,3-dichloropyridine (74 g, 500mmol), 50% hydrazine (250 g, 2.5 mol) and dioxane (300 mL) were added sequentially. The temperature of the reaction mixture was heated to reflux for 20 hours. Then the reaction mixture was cooled down to room temperature overnight and white crystal was precipitated. The white crystal was isolated via filtration and dried to give the product (51 g) as a white solid in 71% yield. 1H NMR (300MHz, CDCl3): 8.113-8.092 (d, 1H), 7.493-7.463 (d, 1H), 6.672-6.630 (q, 1H), 6.237 (s, 1H), 3.905 (s, 2H). (7) Synthesis of ethyl 2-(3-chloropyridin-2-yl)-5-oxopyrazolidine-3-carboxylate: To a 1000 mL flask 300 mL anhydrous ethanol, sodium ethoxide (15.6 g, 0.229 mol) and 3-chloro-2-hydrazinylpyridine (30.0 g, 0.208mol) were added. The reaction mixture was heated to reflux for 5 minutes. Diethyl maleate (36.0 g, 0.250 mmol) was added dropwise and heated to reflux for 10 minutes. After being cooled to 65?, the reaction mixture was neutralized with glacial acetic acid (25.2 g, 0.420mol) and diluted with 300mL water. The reaction mixture was cooled down to room temperature, and the aprecipitate formed. The product was isolated via filtration, washed with 40% aqueous solution of ethanol (3 × 50 mL) and dried to give the product (26.3g) as an orange solid in 42% yield. 1H NMR (300MHz, DMSO): 8.289-8.269 (q, 1H), 7.956-7.190 (q, 1H), 7.231-7.190 (q, 1H), 4.862-4.816 (q, 1H), 4.236-4.165 (q, 2H), 2.967-2.879 (q, 1H), 2.396-2.336 (q, 1H), 1.250-1.202 (t, 3H). (8) Synthesis of ethyl 3-chloro-1-(3-chloropyridin-2-yl)-4, 5-dihydro-1H-pyrazole-5-carboxylate: To a 100 mL flask acetonitrile (65 mL), ethyl 2-(3-chloropyridin-2-yl)-5-oxopyrazolidine-3-carboxylate (6.5 g, 24 mmol) and phosphoryl chloride (4.4 g, 28.8 mmol) were added. The reaction mixture was heated to reflux for 2 hours. The reaction mixture was distilled to remove 30 mL solvent.The concentrated reaction mixture was added to the mixture of sodium carbonate (10.1 g, 120 mmol) and water (40 mL). The reaction mixture was stirred for 20 minutes until no more gas released. The reaction mixture was diluted with 100 mL dichloromethane and stirred for 50 minutes. The mixture was extracted with dichloromethane (3 × 100 mL). The organic extracts were washed with water, dried over anhydrous magnesium sulfate and concentrated by rotary evaporator to give the product (4.7 g) as a dark amber oil in 68% yield. 1H NMR (300MHz, DMSO): 8.129-8.108 (q, 1H), 7.866-7.834 (q, 1H), 7.017-6.975 (q, 1H), 5.275-5.207 (q, 1H), 4.150-4.078 (q, 2H), 3.648-3.504 (m, 1H), 3.298-3.211 (m, 1H), 1.174-1.127 (t, 3H). (9) Synthesis of ethyl 3-chloro-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylate: To a 100 mL flask ethyl 3-chloro-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate (4.0 g, 13.9 mmol), acetonitrile (10 mL) and 98% sulfuric acid (2.8 g, 27.8mmol) were added. The reaction mixture was stirred for a few minutes. Then the potassium persulfate (6.0 g, 22.2mmol) was added. The reaction mixture was heated to reflux for 5 hours. The resulting orange slurry was filtered while still warm (50-65?) to remove a white precipitate. The filter cake was washed with acetonitrile (10 mL). The filtrate was concentrated to about 10 mL on rotary evaporator. Then 50 mL water was added. The solid product was removed by filtration, washed with 25% aqueous solution of acetonitrile (3 × 15 mL) and dried to give the product (3.2 g) as an orange solid in 80% yield. 1H NMR (300MHz, DMSO): 8.521-8.500 (d, 1H), 7.963-7.930 (d, 1H), 7.511-7.469 (q, 1H), 6.950 (s, 1H), 4.258-4.187 (q, 2H), 1.242-1.195 (t, 3H). (10) Synthesis of 3-chloro-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid: To a 100 mL flask ethyl 3-chloro-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylate (1.8 g, 6.3 mmol) and methanol (10 mL), water (10 mL) and sodium hydroxide (0.3 g, 6.9 mmol) were added. After being strried for 1 hour at room temperature, all of the starting materials had dissolved. The reaction mixture was concentrated to about 10 mL dark brown solution by rotary evaporator. Then 40 mL water was added. The aqueous solution was extracted with ethyl ether (50 mL) and acidified with concentrated hydrochloric acid to pH=4. The solid product was isolated via filtration, washed with 2 × 50 mL water and dried to give the product (1.4 g) as a white solid in 88% yield. 1H NMR (300MHz, DMSO): 8.578-8.566 (d, 1H), 8.278-8.251 (d, 1H), 7.719-7.677 (q, 1H), 7.234 (s, 1H). (11) Synthesis of 3-chloro-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carbonyl chloride: To a 100 mL flask 3-chloro-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid (15.0 g, 58.1 mmol), dichloromethane (100 mL) and oxalyl dichloride (11.1 g, 87.2 mmol) were added. After five drops of N, N-dimethyl formamide was added, a large number of gas was released. After being stirred for 8 hours at room temperature, the reaction mixture was evaporated to dryness at reduced pressure. Then 100 mL toluene was added, and the reaction mixture was concentrated again under vacuum to give the the product (16 g) as a green solid in 100% yield. (12) Synthesis of compound 1.2: To a 100 mL flask 2-amino-5-chloro-N-(1-cyanoethyl)-3-methylbenzamide (2.0 g, 8.4 mmol), dichloromethane (20 mL), 3-chloro-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carbonyl chloride (2.8 g, 10.1 mmol) and triethylamine (1.1 g, 10.9 mmol) were added. The reaction mixture was stirred for 3 hours at room temperature .Then the reaction mixture was poured into100 mL of water, extracted with ethyl acetate (2×100 mL). The organic extracts were washed with saturated sodium carbonate solution and brine, dried over anhydrous magnesium sulfate and concentrated by rotary evaporator. The residue was purified by chromatography on silica gel column chromatography (fluent: ethyl acetate/petroleum ether=1/2) to give the compound 1.2 (2.3 g) as a white solid in 58% yield. EXAMPLE 2: SYNTHSIS OF COMPOUND 1.14 (1) Synthesis of 2-amino-2-methylpropanenitrile: To a 250 mL flask sodium cyanide (4.95 g, 100 mmol) and ammonia hydrate (60 mL) were added. After being stirred at room temperature, sodium cyanide has dissolved completely, acetone (5.84 g, 100 mmol) and ammonium chloride (5.38 g, 100 mmol) were added. The reaction mixture was reacting for 48 hours at room temperature. The reaction mixture was extracted with dichloromethane for 3 times (50 mL, 10 mL, 10 mL). The combined organic extracts were dried over anhydrous magnesium sulfate and concentrated under vacuum to give the the product (5.25 g) as a colorless oil in 57% yield. (2) Synthesis of N-(2-cyanopropan-2-yl) -3-methyl-2-nitrobenzamide: To a 500 mL flask 3-methyl-2-nitrobenzoyl chloride (21.0 g, 105 mmol), dichloromethane (100 mL) and 2-amino-2-methylpropanenitrile (8.8 g, 105 mmol) were added sequentially. After triethylamine (12.6 g, 126 mmol) was added dropwise, the reaction mixture was stirred for 3 hours at room temperature. Then the reaction mixture was poured into 200 mL water, extracted with ethyl acetate (3×100 mL). The combined organic extracts were washed with saturated sodium carbonate solution and brine, dried over anhydrous magnesium sulfate, and concentrated to give the the product (19.2 g) as a white solid in 74% yield. (3) Synthesis of 2-amino-N-(2-cyanopropan-2-yl)-3-methylbenzamide (Compound 2.11): To a 250 mL flask N-(2-cyanopropan-2-yl)-3-methyl-2-nitrobenzamide (6.4 g, 25.9 mmol), acetic acid (80 mL) and iron powder (5.8 g, 103.6 mmol) were added sequentially. The reaction temperature was controlled under 80?. The reaction mixture was stirred for 3 hours. After being cooled down to room temperature, 100 mL water was added and the reaction solution was extracted with ethyl acetate (3×100 mL). The organic layer was washed with water and brine, dried over anhydrous magnesium sulfate, and concentrated to give the the product (4.5 g) as a brown yellow solid in 80% yield. (4) Synthesis of 2-amino-5-chloro-N-(2-cyanopropan-2-yl)-3-methylbenzamide (Compound 2.12): To a 150 mL flask 2-amino-N-(2-cyanopropan-2-yl)-3-methylbenzamide (4.3 g, 19.8 mmol), NCS (2.7g, 19.8 mmol) and dimethylformamide (50 mL) were added sequentially. The reaction mixture was stirred for 30 minutes at 100-110?. After being cooled down to room temperature, the reaction mixture was poured into 100 mL water and extracted with ethyl acetate (3×100 mL). The organic extracts were washed with water and brine, dried over anhydrous magnesium sulfate, and concentrated to give the product (4.0 g) as a black solid in 80% yield. 1H NMR (300MHz, CDCl3): 7.145-7.126 (m, 2H), 6.054 (s, 1H), 2.143 (s, 3H), 1.807 (s, 6H). (5) Synthesis of ethyl 3-bromo-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate: To a 150 mL flask acetonitrile (65 mL), ethyl 2-(3-chloropyridin-2-yl)-5-oxopyrazolidine-3-carboxylate (5.0 g, 18.5mmol) and phosphoryl bromide (3.4 g, 11.9 mmol) were added. The temperature of the reaction mixture was heated to reflux for 2 hours. The reaction mixture was distilled to remove 30 mL solvent and added to mixture of sodium carbonate (10.1 g, 120 mmol) and water (40 mL). The mixture was stirred for 20 minutes at which time gas evolution had ceased. The reaction mixture was diluted with dichloromethane (100 mL), stirred for 50 minutes and extracted with dichloromethane (3 × 100 mL). The organic extracts were washed with water, dried over anhydrous magnesium sulfate, and concentrated by rotary evaporator to give the product (6.0 g) as a amber oil in 97% yield. 1H NMR: 8.093-8.073 (q, 1H), 7.681-7.650 (q, 1H), 6.892-6.851 (q, 1H), 5.293-5.224 (q, 1H), 4.220-4.150 (q, 2H), 3.502-3.404 (q, 1H), 3.291-3.202 (q, 1H), 1.226-1.179 (t, 3H). (6) Synthesis of ethyl 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylate: : To a 100 mL flask ethyl 3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxylate (4.0 g, 12.0 mmol), acetonitrile (10 mL) and 98% sulfuric acid (2.4 g, 24.0 mmol) were added. The mixture was stirred for a few minutes, and potassium persulfate (5.2 g, 19.2mmol) was added. The reaction mixture was heated to reflux for 5 hours. The resulting orange slurry while still warm (50-65?) was filtered to remove a white precipitat. Filter cake was washed by acetonitrile (10 mL). The filtrate was concentrated to about 10 mL on rotary evaporator. Then water (50 mL) was added. The solid product was isolated by filtration, washed with 25% aqueous solution of acetonitrile (3 × 15 mL) and dried to give the product (3.8 g) as an orange solid in 95% yield. 1H NMR (300MHz, CDCl): 8.522-8.501 (q, 1H), 7.927-7.895 (q, 1H), 7.465-7.424 (q, 1H), 7.034 (s, 1H), 4.262-4.190 (q, 2H), 1.240-1.192 (t, 3H). (7) Synthesis of ethyl 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid: To a 100 mL flask ethyl 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylate (1.4 g, 4.2mmol), methanol (10 mL), water (10 mL) and sodium hydroxide (0.2g, 4.6mmol) were added. The reaction mixture was stirred at room temperature for 1 hour, and all starting materials were dissolved. The reaction mixture was concentrated by rotary evaporator to about 10 mL dark brown solution. Then 40 mL water was added. Aqueous solution was extracted with ethyl ether (50 mL) and acidified with concentrated hydrochloric acid to pH=4. The solid product was isolated by filtration washed with water (2 × 50 mL) and dried to give the product (1.1 g) as a white solid in 85% yield. (8) Synthesis of 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carbonyl chloride: To a 100 mL flask 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid (0.9 g, 2.8 mmol), dichloromethane (10 mL) and oxalyl dichloride (0.7 g, 5.6 mmol) were added. After two drops of N,N-dimethyl formamide were added, a large number of gas was released. After stirring for 8 hours at room temperature, the reaction mixture was evaporated to dryness at reduced pressure. Then 50 mL toluene was added, and the reaction mixture was concentrated again under vacuum to give the product (0.9 g) as an oil in 100% yield. (9) Synthesis of compound 1.14: To a 100 mL flask 2-amino-5-chloro-N-(2-cyanopropan-2-yl)-3-methylbenzamide (0.64 g, 2.0mmol), dichloromethane (20 mL), 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carbonyl chloride (0.5 g, 2.0 mmol) and triethylamine (0.24 g, 2.4 mmol) were added. The reaction mixture was stirred for 3 hours at room temperature. Then reaction mixture was poured into water (100 mL), extracted with ethyl acetate (2×100 mL). The organic extracts were washed with saturated sodium carbonate solution and brine, dried over anhydrous magnesium sulfate and concentrated by rotary evaporator. The residue was purified by chromatography on silica gel column chromatography (fluent: ethyl acetate/petroleum ether=1/2) to give the compound 1.14 (0.4 g) as a white solid in 40% yield. EXAMPLE 3: SYNTHSIS OF COMPOUND 1.17 To a 100 mL flask 2-amino-3,5-dichloro-N-(2-cyanopropan-2-yl)benzamide (0.51 g, 1.83 mmol) and dichloromethane (20 mL), 3-chloro-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carbonyl chloride (0.5 g, 1.83 mmol) and triethylamine (0.22 g, 2.2 mmol) were added. The reaction mixture was stirred for 3 hours at room temperature .Then the reaction mixture was poured into water (100 mL), extracted with ethyl acetate (2×100 mL). The organic extracts were washed with saturated sodium carbonate solution and brine, dried over anhydrous magnesium sulfate and concentrated by rotary evaporator. The residue was purified by chromatography on silica gel column chromatography (fluent: ethyl acetate/petroleum ether=1/2) to give the compound 1.17 (0.35 g) as a white solid in 38% yield. EXAMPLE 4: SYNTHSIS OF COMPOUND 1.19 (1) Synthesis of ethyl 2-(3-chlorophenyl)-5-oxopyrazolidine-3-carboxylate: To a 1000 mL flask anhydrous ethanol (300 mL), sodium ethoxide (35.7 g, 0.525 mol) and (2-chlorophenyl) hydrazine (71.5 g, 0.500 mol) were added. The temperature of the reaction mixture was heated to reflux for 5 minutes. Diethyl maleate (82.8 g, 0.575 mmol) was added dropwise and the mixture was re-heated to reflux for 10 minutes. After cooling to 65?, the reaction mixture was neutralized with glacial acetic acid (57.6 g, 0.961 mol) and diluted with water (400 mL). After being cooled to room temperature, aprecipitate formed. The solid was isolated by filtration, washed with 40% aqueous solution of ethanol (3 × 50 mL) and dried to give the product (64 g) as a solid in 48% yield. 1H NMR (300MHz, DMSO): 10.129 (s, 1H), 7.418-7.392 (d, 1H), 7.311-7.265 (m, 2H), 7.129-7.072 (m, 1H), 4.385-4.317 (q, 1H), 4.239-4.167 (q, 2H), 3.040-2.952 (q, 1H), 2.276-2.221 (q, 1H), 1.290-1.214 (t, 3H)? (2) Synthesis of ethyl 3-chloro-1-(2-chlorophenyl)-4,5-dihydro-1H-pyrazole-5-carboxylate: To a 100 mL flask acetonitrile (50 mL), ethyl 2-(2-chlorophenyl)-5-oxopyrazolidine-3-carboxylate (5.0 g, 16.7 mmol) and phosphoryl chloride (2.9 g, 16.7 mmol) were added. The reaction mixture was heated to reflux for 2 hours. The reaction mixture was distilled to remove 30 mL solvent and added to the mixture of sodium carbonate (10.1 g, 120 mmol) and water (40 mL). The mixture was stirred for 20 minutes at which time gas evolution had ceased. The reaction mixture was diluted with dichloromethane (100 mL), stirred for 50 minutes and extracted with dichloromethane (3 × 100 mL). The organic extracts were washed with water, dried over anhydrous magnesium sulfate and concentrated by rotary evaporator to give the product (2.8 g) as an oil in 58% yield. 1H NMR (300MHz, CDCl3): 7.437-7.404 (q, 1H), 7.336-7.304 (m, 1H), 7.243-7.187 (m, 1H), 7.079-7.023 (m, 1H), 5.314-5.262 (q, 1H), 3.992-3.920 (q, 2H), 3.544-3.449 (q, 1H), 3.357-3.285 (q, 1H), 1.008-0.961 (t, 3H). (3) Synthesis of ethyl 3-chloro-1-(2-chlorophenyl)-1H-pyrazole-5-carboxylate: To a 100 mL flask ethyl 3-chloro-1-(2-chlorophenyl)-4,5-dihydro-1H-pyrazole-5-carboxylate (2.8 g, 10.0 mmol), acetonitrile (30 mL) and 98% sulfuric acid (2.0 g, 20.0 mmol) were added. The mixture was stirred for a few minutes, and potassium persulfate (4.3g, 16.0mmol) was added. The reaction mixture was heated to reflux for 5 hours. The resulting orange slurry while still warm (50-65?) was filtered to remove the white precipitat. Filter cake was washed by acetonitrile (10 mL). The filtrate was concentrated to about 10 mL on rotary evaporator. Then water (50 mL) was added. The solid product was isolated by filtration, washed with 25% aqueous solution of acetonitrile (3 × 15 mL) and dried to give the product (1.6 g) as orange solid in 56% yield. 1H NMR (300MHz, DMSO): 7.528-7.438 (m, 4H), 6.930 (s, 1H), 4.177-4.132 (q, 2H), 1.207-1.159 (t, 3H). (4) Synthesis of 3-chloro-1-(2-chlorophenyl)-1H-pyrazole-5-carboxylic acid: To a 100 mL flask ethyl 3-chloro-1-(2-chlorophenyl)-1H-pyrazole-5-carboxylate (1.6 g, 5.6 mmol), methanol (10 mL), water (10 mL) and sodium hydroxide (0.27 g, 6.7 mmol) were added. The mixture was stirred at room temperature for 1 hour, and all starting materials were dissolved. The reaction mixture was concentrated to about 10 mL dark brown solution on rotary evaporator. Then 40 mL water was added. Aqueous solution was extracted with ethyl ether (50 mL) and acidified with concentrated hydrochloric acid to pH=4. The solid product was isolated by filtration, washed with water (2 × 50 mL) and dried to give the product (1.1 g) as a white solid in 79% yield. 1H NMR (300MHz, DMSO): 7.623-7.049 (m, 4H), 7.049 (s, 1H). (5) Synthesis of 3-chloro-1-(2-chlorophenyl)-1H-pyrazole-5-carbonyl chloride: To a 50 mL flask 3-chloro-1-(2-chlorophenyl)-1H-pyrazole-5-carboxylic acid (1.1 g, 4.3 mmol) and 20 mL dichloromethane and oxalyl dichloride (0.8 g, 6.4 mmol) were added. After one drop of N,N-dimethyl formamide was added, a large number of gas was released. After being stirred for 8 hours at room temperature, the reaction mixture was evaporated to dryness at reduced pressure. Then 20 mL toluene was added, and the reaction mixture was concentrated under vacuum to give the product (1.2 g) as an oil in 100% yield. (6) Synthesis of compound 1.19: To a 50 mL flask 2-amino-5-chloro-N-(2-cyanopropan-2-yl)-3-methylbenzamide (0.3 g, 1.2 mmol), dichloromethane (10 mL), 3-chloro-1-(2-chlorophenyl)-1H-pyrazole-5-carbonyl chloride (0.33 g, 1.2 mmol) and triethylamine (0.14 g, 1.4 mmol) were added. The reaction mixture was stirred for 3 hours at room temperature. Then reaction mixture was poured into water (50 mL), and extracted with ethyl acetate (2 × 50 mL). The organic extracts were washed with saturated sodium carbonate solution and brine, dried over anhydrous magnesium sulfate and concentrated by rotary evaporator. The residue was purified by chromatography on silica gel column chromatography (fluent: ethyl acetate/petroleum ether=1/2) to give the compound 1.19 (0.4 g) as a white solid in 68% yield. EXAMPLE 5: SYNTHSIS OF COMPOUND 1.24 (1) Synthesis of N'-(2-chlorophenyl)-2,2,2-trifluoroacetohydrazide: To a flask-3-neck (2-chlorophenyl) hydrazine (10.0 g, 70.4 mmol) and tetrahydrofuran (80 mL) were added sequentially. To the mixture 2,2,2-trifluoroacetic anhydride (14.6g, 70.4 mmol) in tetrahydrofuran (20 mL) was added dropwise, and the reaction mixture was reacted for 3 hours at room temperature . The reaction mixture was distilled to remove solvent and poured into 50 mL water, extracted with ethyl acetate (100 mL). The organic extracts were washed with 50 mL saturated sodium carbonate solution and 50 mL brine solution, dried over anhydrous magnesium sulfate, and evaporated to dryness at reduced pressure to give the product (15.7 g) as a yellow solid in 93% yield. 1H NMR (300MHz, CDCl3): 8.750 (br s, 1H), 7.306 (dd, 1H), 7.145 (dd, 1H), 6.947 (dd, 1H), 6.815 (dd, 1H), 6.590 (br s, 1H). (2) Synthesis of (Z)-N'-(2-chlorophenyl)-2,2,2-trifluoroacetohydrazonic methanesulfonic anhydride: To a flask-3-neck N'-(2-chlorophenyl)-2,2,2-trifluoroacetohydrazide (5.00 g, 29.1 mmol) and ethyl acetate (50 mL) were added sequentially. And methanesulfonyl chloride (3.8 g, 32.5 mmol) was added dropwise over a period of 30 minutes at 0?. After the reaction mixture was stirred for 30 minutes, triethylamine (4.11g, 40.6 mmol) were added dropwise and then white solid precipitated. The reaction mixture was stirred at room temperature until the reaction mixture reacted completely. The reaction mixture was poured into 50 mL water, extracted with 100 mL ethyl acetate. The organic extracts were washed with 50 mL brine, dried over anhydrous magnesium sulfate, and evaprorated to dryness at reduced pressure to give the product (4.2 g) as a viscous yellow solid in 59% yield. 1H NMR (300MHz, CDCl3): 8.854 (br s, 1H), 7.526 (dd, 1H), 7.327-7.231 (m, 2H), 6.944 (dd, 1H), 3.402 (s, 3H). (3) Synthesis of ethyl 1-(2-chlorophenyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazole-5-carboxylate: To a flask-3-neck the product of above step (2.00 g, 7.60 mmol), toluene (20 mL) and ethyl acrylate (1.53 g, 15.2 mmol) were added sequentially. And triethylamine (0.92 g, 9.14 mmol) was added dropwise over a period of 10 minutes at 0?. The reaction mixture was reacted at room temperature overnight until the reaction mixture reacted completely and the colour of the solution changed from yellow to brown. The reaction mixture was poured into 50 mL water, extracted with ethyl acetate (100 mL). The organic extracts were washed with 50 mL saturated sodium carbonate solution and 50 mL brine, dried over anhydrous magnesium sulfate, and evaprorated to dryness at reduced pressure. After separation through silica gel column chromatography, 0.8 g yellow oil was gained in 36% yield. 1H NMR(300MHz, CDCl3): 7.439 (br s, 1H), 7.349 (dd, 1H), 7.261 (dd, 1H), 7.118 (dd, 1H), 5.463 (dd, 1H), 3.966 (q, 2H), 3.449-3.384 (m, 2H), 0.993 (t, 3H). (4) Synthesis of ethyl 1-(2-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylate: To a flask-3-neck ethyl 1-(2-chlorophenyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazole-5-carboxylate (1.00 g, 3.48 mmol) and 10 mL tetrahydrofuran were added sequentially and N-chloro succinimide (0.51 g, 3.48 mmol) was added portionwise at room temperature. The reaction mixture was reacted at room temperature for 10 minutes and the colour of the solution changed from yellow to black. After 4 hours, the reaction mixture was poured into 50 mL water, extracted with ethyl acetate (100 mL). The organic extracts were washed with 50 mL saturated sodium carbonate solution and 50 mL brine, dried over anhydrous magnesium sulfate and evaprorated at reduced pressure. After separation through silica gel column chromatography, 0.6 g yellow oil was gained in 61% yield. 1H NMR (300MHz, CDCl3): 7.548-7.397 (m, 4H), 7.285 (s, 1H), 4.231 (q, 2H), 1.238 (t, 3H). (5) Synthesis of 1-(2-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid: To a single-neck-flask ethyl 1-(2-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylate (1.20 g, 3.72 mmol), tetrahydrofuran (10 mL) and 10 mL aqueous solution of sodium hydroxide (0.16 g, 3.72 mmol) were added sequentially. The reaction mixture was heated to 30?. The reaction mixture reacted until TLC (fluent: ethyl acetate/petroleum ether=1/1) showed that it reacted completely. The reaction mixture was poured into 50 mL water, extracted with 100 mL ethyl acetate. The aqueous layer was acidified with concentrated hydrochloric acid to pH=2-3 and extracted with 150 mL ethyl acetate. The organic extracts were washed with brine (3×50 mL), dried over anhydrous magnesium sulfate and concentrated to give the product (0.89 g) as a white solid in 82% yield. 1H NMR (300MHz, CDCl3): 7.543-7.418 (m, 4H), 7.348 (s, 1H). (6) Synthesis of 1-(2-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carbonyl chloride: To a single-neck-flask 1-(2-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid (0.40 g, 1.36 mmol), dichloromethane (10 mL) and oxalyl dichloride (0.34 g, 2.72 mmol) were added sequentially. The reaction mixture was stirred for 1 hour at room temperature and the gas bubbles became less. After one drop of N,N-dimethyl formamide was added, a large number of gas was released. The reaction mixture was stirred for 4-6 hours until there was no more gas bubbles to give off. When it reacted completely, the reaction mixture was evaprorated to dryness at reduced pressure. Then toluene was added, and the reaction mixture was concentrated under vacuum to give the product (0.6 g) as a yellow solid in 100% yield. (7) Synthesis of compound 1.24: To a 100 mL flask 2-amino-3,5-dichloro-N-(2-cyanopropan-2-yl)benzamide (0.52 g, 1.1 mmol), 20 mL dichloromethane and 1-(2-chlorophenyl)-3- trifluoromethyl-1H-pyrazole-5-carbonyl chloride (0.6 g, 1.1 mmol) and pyridine (0.15 g, 1.1 mmol) were added. The reaction mixture was stirred for 3 hours at room temperature. Then the reaction mixture was poured into 100 mL water, extracted with ethyl acetate (2×100 mL). The organic extracts were washed with saturated sodium carbonate solution and brine, dried over anhydrous magnesium sulfate and concentrated by rotary evaporator. The residue was purified by chromatography on silica gel column chromatography (fluent: ethyl acetate/petroleum ether=1/2) to give the compound 1.24 (0.4 g) as a white solid in 38% yield. BIOLOGICAL TEST EXAMPLES EXAMPLE 6 INSECTICIDAL ACTIVITY TESTS: According to the solubility of test compounds, the original pesticides are dissolved in acetone or dimethyl sulfoxide, and then diluted with 1 ‰ solution of Tween 80 to the test liquid 50 ml, the content of acetone or dimethyl sulfoxide in the total solution is not more than 10%. Exp. 6.1 Test against Diamondback moth (Plutella xylostella) The cabbage leaves were perforated to get 1 cm diameter leaf discs by the hole puncher. Certain concentrations of test comopounds were sprayed on both sides of the discs at the spray volume of 0.5 mL by Airbrush spraying treatment. Ten test insects (2 years) were introduced on each treatment after drying. Each treatment repeated 3 times. The treated discs were placed in a chamber of 24?, 60%-70% relative humidity, no light. After 96 h, the number of surviving insects was investigated and the mortality rates were calculated. In this test, the following compounds exhibite mortality 90% or more against diamondback moth at 150 ppm: 1.1?1.2?1.14a?1.14?1.25a?1.26. The following compounds exhibite mortality 90% or more against diamondback moth at 40 ppm: 1.1?1.2?1.14a?1.26. The following compounds exhibite mortality 90% or more against diamondback moth at 10 ppm: 1.1,1.14,1.16. Exp. 6.2 Test against Beet armyworm (Laphygma exigua Hubner) The cabbage leaves were perforated to get 1 cm diameter leaf discs by the hole puncher. Certain concentrations of test comopounds were sprayed on both sides of the discs at the spray volume of 0.5 ml by Airbrush. Ten test insects (3 years) were introduced on each treatment after drying. Each treatment repeated 3 times. The treated discs were placed in a chamber of 24?, 60%-70% relative humidity, no light. After 96 h, the number of surviving insects was investigated and the mortality rates were calculated. In this test, the following compounds exhibite mortality 100% against Beet armyworm at 20 ppm: 1.23. The following compounds exhibite mortality 90% or more against Beet armyworm at 1 ppm: 1.1?1.2?1.3?1.4?1.5?1.6?1.7?1.8?1.9?1.10?1.11? 1.14?1.15?1.16?1.17?1.18?1.19?1.20?1.21?1.24?1.27. The following compounds exhibite mortality 90% or more against Beet armyworm at 0.2 ppm: 1.1?1.4?1.14?1.15?1.18?1.19?1.21?1.24. According to above method, compound 1.14 and KC (compound D477 in the patent WO03/015518A1) were choosed to parallel test the activity against Beet armyworm. The result was listed in table 3. Table 3: Parallel test result of compounds 1.14 and KC against Beet armyworm (mortality, %) Concentration(ppm) mortality Compounds (%) 0.2 0.1 1.14 100 87.5 KC 87.5 50 The structure of compound KC is shown as follows: KC Exp. 7 Fungicidal activity tests According to the solubility of test compounds, the original pesticides are dissolved in acetone or dimethyl sulfoxide, and then diluted with 1 ‰ solution of Tween 80 to the test liquid 50 ml, the content of acetone or dimethyl sulfoxide in the total solution is not more than 10%. Exp. 7.1 In vitro fungicidal activity test against rice blast ( Pyricularia grisea). The melt AEA culture medium was cooled to 60-70?, and calculated amount of the test compounds were added according to the designed concentration to prapare compound-containing culture medium, the final content of test compound was 25ppm, After the medium cooling down sufficiently, rice blast pathogen of 0.5 cm diameter was inoculated and placed into the growth oven. The evaluation was performed after 10 days of inoculation. The measurement of the diameter of each colony was carried out and the rate of fungi inhibition was calculated. The control efficacies of compound 1.17 against rice blast is over 90%. Exp. 7.2 In vivo fungicidal activity test against cucumber downy mildew: Select a consistent growth of potted cucumber seedlings, neatly cut growing point and two mail leaves reserved. The testing compound solutions were sprayed at 400 ppm. Cucumber downy mildew spore suspension was inoculated at the second day after the treatment of the test materials, then placed in the artificial climate chamber (temperature: day 25 ?, the night 20 ?, relative humidity: 95 ~ 100%) to cultivate, investigating the prevention and control effect after 6 days of moisturizing cultivation, recorded the onset of disease in 6 levels, calculated prevention control effect according to disease index. The protective controlling effect of compound 1.14 against cucumber downy mildew is more than 90%. We Cliams 1. A benzamide compounds characterized as indicated by formula I: I Wherein: R1 is H or C1-C6 alkyl; R2 is H or C1-C6 alkyl; R3 is C1-C6 alkyl or C3-C6 cycloalkyl, the hydrogen group on the all substituents can also be further substituted by the following groups: halogen, NO2, C1-C3 alkoxy, phenoxy, C1-C3 alkylthio, C1-C3 alkylsulfinyl or C1-C3 alkylsulfonyl; Or R2 and R3 are connected to the same carbon together to form C3-C6 cycloalkyl; R4 is H, halogen or CN; R5 is halogen or C1-C3 alkyl; R6 is halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy or C1-C3 haloalkoxy; R7 is H, halogen, CN, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 alkylthio, C1-C3 alkylsulfinyl or C1-C3 alkylsulfonyl; R8 is halogen, CN, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy or C1-C3 alkythio; X is CH, CF, CCl or N. 2. The compounds according to the claim 1, characterized in that wherein: R1 is H; R2 is H or C1-C3 alkyl; R3 is C1-C3 alkyl; Or R2 and R3 are connected to the same carbon together to form C3-C6 cycloalkyl; R4 is H, halogen or CN; R5 is halogen or C1-C3 alkyl; R6 is halogen or C1-C3 haloalkyl; R7 is H, halogen, CN or C1-C3 haloalkyl; R8 is halogen; X is CH, CF, CCl or N. 3. The compounds according to the claim 2, characterized in that wherein: R1 is H; R2 is H or methyl; R3 is methyl; R4 is Cl, Br, I, or CN; R5 is Cl, Br or methyl; R6 is Cl, Br or CF3; R7 is H, Cl or CF3; R8 is Cl; X is CH, CF, CCl or N. 4. An intermediate to prepare the compounds of claim 1 characterized as indicated by formula II: II Wherein: R1 is H or C1-C6 alkyl; R2 is H or C1-C6 alkyl; R3 is C1-C6 alkyl or C3-C6 cycloalkyl, the hydrogen group on the all substituents can also be further substituted by the following groups: halogen, NO2, C1-C3 alkoxy, phenoxy, C1-C3 alkylthio, C1-C3 alkylsulfinyl or C1-C3 alkylsulfonyl; Or R2 and R3 are connected to the same carbon together to form C3-C6 cycloalkyl; R4 is H, halogen or CN; R5 is halogen or C1-C3 alkyl. 5. The formula I compounds according to the claim1 are used to control insects. 6. The formula I compounds according to the claim1 are used to control diseases. 7. A fungicidal or insecticidal composition, characterized in that wherein: comprising the characterised compounds of formula I of the claim 1 and an acceptable carrier in agriculture, forestry or public health, in which the weight percentage of active ingredient(s) is 1%-99%. 8. A method for controlling insects, characterized in that wherein: applying the composition of claim 7 to pests or its growth medium with effective dosage within a range of from 10 g/ha to 1000 g/ha. 9. A method for controlling diseases, characterized in that wherein: applying the composition of claim 7 to diseases or its growth medium with effective dosage within a range of from 100 g/ha to 2000 g/ha. 10. A Benzamide Compounds And Applications Thereof is claimed substantially as herein described with forgoing description Dated this 29th day of September 2009.

Full Text

FORM 2
THE PATENTS ACT 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rule 13)

1. ' BENZAMIDE COMPOUNDS AND APPLICATIONS THEREOF '

2.

1. (A) SINOCHEM CORPORATION
(B) A Company incorporated under the laws of China.
(C) 6-12F Central Tower, Chemsunny World Trade Center, 28 Fuxingmennei Dajie,
Beijing 100045 China

2. (A) SHENYANG RESEARCH INSTITUTE OF CHEMICAL INDUSTRY_CO.,
LTD
(B) A Company incorporated under the laws of China.
(C) 8 Shenliaodong Road, Tiexi District, Shenyang Liaoning 110021 China

The following specification particularly describes the invention and the manner in which it is to be performed.

BENZAMIDE COMPOUNDS AND APPLICATIONS THEREOF

FIELD OF THE INVENTION
This invention belongs to the field of insecticide and fungicide, relates to benzamide compounds and applications thereof.
BACKGROUND OF THE INVENTION
The search for the novel and improved fungicidal and insecticidal compounds and compositions is continually needed because of the emergence and development of the fungi and insect resistance to the existing fungicides and insecticides after a period of applications.
Some insecticidal benzamides were disclosed in WO03/015518A1, which are highly effective against fall armyworm (Spodoptera frugiperda) at 50 ppm.
Neither the preparation of cyanoalkyl substituted benzamides, nor their fungicidal or insecticidal activities according to the present invention are described in any literature.

SUMMARY OF THE INVENTION
The purpose of this invention is to provide a kind of novel benzamides, and their applications as fungicides or insecticides.
The technical embodiment of this invention is as follows:
The present invention provides a kind of benzamides as represented by formula I:

I
Wherein:
R1 is H or C1-C6 alkyl;
R2 is H or C1-C6 alkyl;
R3 is C1-C6 alkyl or C3-C6 cycloalkyl, the hydrogen group on the all substituents can also be further substituted by the following groups: halogen, NO2, C1-C3 alkoxy, phenoxy, C1-C3 alkylthio, C1-C3 alkylsulfinyl or C1-C3 alkylsulfonyl;
Or R2 and R3 form C3-C6 cycloalkyl together with their connected carbon;
R4 is H, halogen or CN;
R5 is halogen or C1-C3 alkyl;
R6 is halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy or C1-C3 haloalkoxy;
R7 is H, halogen, CN, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 alkylthio, C1-C3 alkylsulfinyl or C1-C3 alkylsulfonyl;
R8 is halogen, CN, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy or C1-C3 alkythio;
X is CH, CF, CCl or N.

The preferred compounds of the formula I in this invention are:
R1 is H;
R2 is H or C1-C3 alkyl;
R3 is C1-C3 alkyl;
Or R2 and R3 form C3-C6 cycloalkyl together with their connected carbon;
R4 is H, halogen or CN;
R5 is halogen or C1-C3 alkyl;
R6 is halogen or C1-C3 haloalkyl;
R7 is H, halogen, CN or C1-C3 haloalkyl;
R8 is halogen;
X is CH, CF, CCl or N.

The more preferred compounds of the formula I in this invention are:
R1 is H;
R2 is H or methyl;
R3 is methyl;
R4 is Cl, Br, I, or CN;
R5 is Cl, Br or methyl;
R6 is Cl, Br or CF3;
R7 is H, Cl or CF3;
R8 is Cl;
X is CH, CF, CCl or N.

This invention further relates to the compounds of formula II for the preparation of the compounds of formula I, which are not described in any literature.

II
Wherein:
R1 is H or C1-C6 alkyl;
R2 is H or C1-C6 alkyl;
R3 is C1-C6 alkyl or C3-C6 cycloalkyl, the hydrogen group on the all substituents can also be further substituted by the following groups: halogen, NO2, C1-C3 alkoxy, phenoxy, C1-C3 alkylthio, C1-C3 alkylsulfinyl or C1-C3 alkylsulfonyl;
Or R2 and R3 form C3-C6 cycloalkyl together with their connected carbon;
R4 is H, halogen or CN;
R5 is halogen or C1-C3 alkyl;

In above definations of the compounds of formula I, the term “alkyl” indicates straight or branched alkyl such as methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, n-pentyl, i-pentyl, n-hexyl, etc.. “Cycloalkyl” includes, for example, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl, etc.. “Haloalkyl” denotes that alkyl is partially or fully substituted with halogen atoms. “Alkoxy” is that the end of alkyl is oxygen, such as methoxy, ethoxy, n-propyloxy, i-propyloxy, t-butoxy, etc.. “Haloalykoxy” is that the end of the alkyl substituted with one or more halogen atoms is oxygen. “Alkylthio” is that the end of alkyl is the sulfur, such as methylthio, ethylthio etc.. “Alksulfinyl” is that the end of alkyl is the sulfinyl group (SO-), such as methsulfinyl. “Alksulfonyl” is that the end of alkyl is the sulfonyl group (SO2-), such as methsulfonyl. “Halogen” includes fluorine, chlorine, bromine, and iodine.

The compounds of the formula I in the present invention can be prepared by the following processes, and the substituents in the reaction formula are same as above definitions:

II III I
The compounds of formula II and III in an appropriate solvent are reacted to yield the compounds of formula I at a certain temperature between -10 ºC and the boiling point of the solvent for 30 minutes to 48 hours. The appropriate solvent was chosen from dichloromethane, chloroform, carbon tetrachloride, hexane, benzene, toluene, ethyl acetate, acetonitrile, tetrahydrofuran, dioxane, DMF or DMSO etc..
The appropriate base is advantageous to the reaction. The appropriate base was chosen from organic base such as sodium methoxide, sodium tert-butoxide, potassium tert-butoxide, triethylamine, N, N-dimethylaniline, pyridine etc. or inorganic base such as sodium carbonate, potassium carbonate, sodium bicarbonate, sodium hydroxide, or potassium hydroxide etc.
The compounds of the formula II can be prepared by the following processes:

IV II
The nitro compounds IV reacted with reducing agents such as iron, zinc or hydrogen etc. (according to the method described in EPA0083055A2) in an appropriate solvent to obtain the compounds of formula II at a certain temperature between -10 ºC and the boiling point of the solvent for 30 minutes to 48 hours. The appropriate solvents include water, acetic acid, acetone, dichloromethane, chloroform, carbon tetrachloride, hexane, benzene, toluene, ethyl acetate, ethanol, DMF, THF, ioxane or the mixture solvent of above two or three solvents etc..

The compounds of formula II (wherein R4 is H) reacted with halogenation reagent such as halogen, N-chlorosuccinimide etc., in an appropriate solvent to obtain the compounds of formula II (wherein R4 is halogen) at a certain temperature between -10 ºC and the boiling point of the solvent for 30 minutes to 48 hours. The appropriate solvents include dichloromethane, chloroform, carbon tetrachloride, DMF, THF, dioxane or DMSO etc.. The halogens include iodine, bromine or chlorine.
The compounds of formula II (wherein R4 is halogen) reacted with cyanation reagent in the appropriate solvent to obtain the compounds of formula II (wherein R4 is CN) at a certain temperature between -10 ºC and the boiling point of the solvent for 30 minutes to 48 hours. The cyanation reagents include sodium cyanide, potassium cyanide or cuprous cyanide. The appropriate solvents include DMF, THF, dioxane or dimethylsulfoxide etc.. The halogens include iodine, bromine or chlorine.

The compounds of the formula IV can be prepared by the following processes:

V VI IV
The benzoyl chloride V (commercially available, prepared according to the following literature: March J, Advanced Organic Chemistry, 4th Ed, John Wiley & sons, 1992) reacted with aminocyanoalkane VI (commercially available, prepared according to the following literature: J. Peptide Res. 56, 2000, 283-297) in an appropriate solvent to obtain the compounds of formula IV at a certain temperature between -10 ºC and the boiling point of the solvent for 30 minutes to 48 hours. The appropriate solvents include chloroform, dichloromethane, carbon tetrachloride, hexane, benzene, toluene, ethyl acetate, DMF, THF or dioxane etc.. The appropriate base, for example triethylamine, pyridine, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate or sodium bicarbonate etc. is advantageous to the reaction.
The compounds of formula III (pyrazolcarbonyl chloride and the corresponding acid) are prepared according to the following literature: Bioorganic & Medicinal Chemistry Letters, 2005, 15, 4898-4906.
The structures and their physical properties of some representative compounds of formula I are shown in Table 1.

Table 1: The structures and their physical properties of some representative compounds of formula I

Compound R2 R3 R4 R5 R6 R7 R8 X Appearance (m.p.(?))
1.1a H CH3 H CH3 Br H Cl N white solid (146-150)
1.1 H CH3 Cl CH3 Br H Cl N white solid (205-207)
1.2 H CH3 Cl CH3 Cl H Cl N white solid (197-199)
1.3 H CH3 Br CH3 Cl H Cl N white solid (138-140)
1.4 H CH3 Br CH3 Br H Cl N white solid (208-209)
1.5 H CH3 I CH3 Cl H Cl N white solid (135-137)
1.6 H CH3 Cl Cl Cl H Cl N white solid (165-168)
1.7 H CH3 Br Cl Cl H Cl N white solid (167-170)
1.8 H CH3 I Cl Cl H Cl N white solid (168-173)
1.9 H CH3 Cl Cl Br H Cl N white solid (153-156)
1.10 H CH3 Br Cl Br H Cl N white solid (153-157)
1.11 H CH3 I Cl Br H Cl N white solid (154-158)
1.12 H CH3 CN Cl Br H Cl N
1.13 H CH3 CN CH3 Br H Cl N white solid (210-213)
1.14a CH3 CH3 H CH3 Br H Cl N white solid (248-253)
1.14 CH3 CH3 Cl CH3 Br H Cl N white solid (191-194)
1.15 CH3 CH3 Cl CH3 Cl H Cl N white solid (213-216)
1.16 CH3 CH3 Br CH3 Br H Cl N white solid (175-177)
1.17 CH3 CH3 Cl Cl Cl H Cl N white solid (149-151)
1.18 CH3 CH3 Cl Cl Br H Cl N white solid (254-256)
1.19 CH3 CH3 Cl CH3 Cl H Cl CH white solid (252-254)
1.20 CH3 CH3 Br CH3 Cl H Cl CH white solid (248-250)
1.21 CH3 CH3 Br Br Cl H Cl CH white solid (177-180)
1.22 CH3 CH3 CN Cl Br H Cl N
1.23 CH3 CH3 CN CH3 Br H Cl N white solid (140-142)
1.24 CH3 CH3 Cl Cl CF3 H Cl CH white solid (246-248)
1.25a i-C3H7 CH3 H CH3 Br H Cl N white solid (186-188)
1.25 i-C3H7 CH3 Cl CH3 Br H Cl N white solid (204-208)
1.26 i-C3H7 CH3 Cl CH3 Cl H Cl N oil
1.27 i-C3H7 CH3 Cl CH3 Br H Cl CH white solid (120-125)
1.28 CH2 CH2 CH2 CH2 Cl CH3 Cl H Cl N white solid (165-167)
1.29 CH2 CH2 CH2 CH2 Cl CH3 Br H Cl N white solid (252-256)
1.30 CH2 CH2 CH2 CH2 CH2 Cl CH3 Cl H Cl N white solid (226-228)
1.31 CH2 CH2 CH2 CH2 CH2 Cl CH3 Br H Cl N white solid (225-227)

Table 2: The structures and their physical properties of some representative compounds of formula II

Compound R2 R3 R4 R5 Appearance (m.p.(?))
2.1 H CH3 H CH3 white solid (105-106)
2.2 H CH3 Cl CH3 white solid (139-140)
2.3 H CH3 Br CH3 wax
2.4 H CH3 I CH3 wax
2.5 H CH3 H Cl
2.6 H CH3 Cl Cl
2.7 H CH3 Br Cl
2.8 H CH3 I Cl
2.9 H CH3 CN Cl
2.10 H CH3 CN CH3
2.11 CH3 CH3 H CH3 white solid (173-174)
2.12 CH3 CH3 Cl CH3 white solid (199-201)
2.13 CH3 CH3 Br CH3
2.14 CH3 CH3 I CH3 wax
2.15 CH3 CH3 CN Cl
2.16 CH3 CH3 CN CH3
2.17 i-C3H7 CH3 H CH3 wax
2.18 i-C3H7 CH3 Cl CH3 white solid (125-127)
2.19 i-C3H7 CH3 H H white solid (129-130)
2.20 i-C3H7 CH3 Cl Cl
2.21 CH2 CH2CH2CH2 H CH3 white solid (142-143)
2.22 CH2 CH2CH2CH2 Cl CH3 wax
2.23 CH2 CH2CH2CH2CH2 H CH3 white solid (136-138)
2.24 CH2 CH2CH2CH2CH2 Cl CH3 white solid (131-133)

Compounds 1H NMR (300MHz, CDCl3) data:
Compound 1.1a: 9.855 (s, 1H), 8.476-8.454 (q, 1H), 7.879-7.847 (q, 1H), 7.407-7.316 (m, 3H), 7.243-7.169 (m, 1H), 7.036 (s, 1H), 7.626-7.635 (d, 1H), 4.973-4.924 (m, 1H), 2.205 (s, 3H), 1.576-1.552 (d, 3H).
Compound 1.1: 9.663 (s, 1H), 8.463-8.443 (d, 1H), 7.878-7.845 (d, 1H), 7.402-7.359 (m, 1H), 7.280-7.241 (m, 2H), 7.070 (s, 1H), 6.716-6.692 (d, 1H), 4.958-4.908 (m, 1H), 2.175 (s, 3H), 1.589-1.564 (d, 3H).
Compound 1.2: 9.654 (s, 1H), 8.470-8.448 (d, 1H), 7.884-7.853 (d, 1H), 7.410-7.368 (m, 1H), 7.275-7.252 (m, 2H), 6.973 (s, 1H), 6.584-6.558 (d, 1H), 4.986-4.937 (m, 1H), 2.195 (s, 3H), 1.603-1.593 (d, 3H).
Compound 1.3: 9.627 (s, 1H), 8.445-8.424 (d, 1H), 7.870-7.837 (d, 1H), 7.408-7.343 (m, 3H), 6.992 (s, 1H), 6.830-6.804 (d, 1H), 4.919-4.871 (m, 1H), 2.151 (s, 3H), 1.556-1.532 (d, 3H).
Compound 1.4: 9.613 (s, 1H), 8.450-8.428 (d, 1H), 7.870-7.832(d, 1H), 7.413-7.345 (m, 3H), 7.069 (s, 1H), 6.755-6.731 (d, 1H), 4.929-4.880 (m, 1H), 2.157 (s, 3H), 1.564-1.532 (d, 3H).
Compound 1.5: 9.632 (s, 1H), 8.463-8.441 (d, 1H), 7.878-7.847(d, 1H), 7.696-7.597 (m, 2H), 7.402-7.359(m, 1H), 6.948 (s, 1H), 6.443 (s, 1H), 4.996-4.945 (m, 1H), 2.174 (s, 3H), 1.633-1.581 (d, 3H).
Compound 1.6: 8.856 (s, 1H), 8.483-8.461 (d, 1H), 7.958-7.927(d, 1H), 7.548-7.541 (m, 1H), 7.390-7.382(m, 2H), 6.971 (s, 1H), 6.485-6.443 (d, 1H), 4.956-4.905 (m, 1H), 1.560 (s, 3H).
Compound 1.7: 8.867 (s, 1H), 8.467-8.458 (d, 1H), 7.928-7.907(d, 1H), 7.688-7.675 (m, 1H), 7.527-7.520(m, 1H), 7.428-7.400 (m, 1H), 6.971 (s, 1H), 6.483-6.254(m, 1H), 4.965-4.896 (m, 1H), 1.556 (s, 3H).
Compound 1.8: 8.957 (s, 1H), 8.453-8.448 (d, 1H), 7.904-7.871(d, 1H), 7.832 (s, 1H), 7.663 (s,1H), 7.415-7.396 (m, 1H), 6.992 (s, 1H), 6.455 (s, 1H), 4.955-4.932 (m, 1H), 1.563 (s, 3H).
Compound 1.9: 8.875 (s, 1H), 8.465-8.318 (d, 1H), 7.923-7.895 (m, 1H), 7.556 (s, 1H), 7.394-7.376 (m, 2H), 7.056 (s, 1H), 6.523 (s, 1H), 4.958-4.939 (m, 1H), 1.571 (s, 3H).
Compound 1.10: 9.141 (s, 1H), 8.450-8.434 (d, 1H), 7.881-7.855 (d, 1H), 7.543-7.536 (d, 1H), 7.420-7.353 (m, 2H), 7.119 (s, 1H), 6.817-6.791 (d, 1H), 4.885-4.837 (m, 1H), 1.510-1.487 (d, 3H).
Compound 1.11: 8.978 (s, 1H), 8.489-8.464 (d, 1H), 7.923-7.845 (m, 2H), 7.673 (s, 1H), 7.425-7.386 (m, 1H), 7.069 (s, 1H), 6.493 (s, 1H), 4.956-4.913 (m, 1H), 1.569-1.548 (d, 3H).
Compound 1.13: 10.346 (s, 1H), 8.556-8.452 (d, 1H), 7.866-7.834 (m, 1H), 7.749-7.746 (m, 1H), 7.636 (m, 1H), 7.407-7.380 (m, 1H), 7.267 (br, 1H), 7.047 (s, 1H), 4.970 (m, 1H), 2.262 (s, 3H), 1.627-1.614 (d, 3H).
Compound 1.14a: 9.876 (s, 1H), 8.459-8.445 (d, 1H), 7.863-7.837 (d, 1H), 7.397-7.371 (m, 3H), 7.267-7.230 (m, 1H), 7.155 (s, 1H), 6.427 (s, 1H), 2.206 (s, 3H), 1.620 (s, 6H).
Compound 1.14: 9.699 (s, 1H), 8.435-8.414 (d, 1H), 7.860-7.829 (d, 1H), 7.387-7.345 (m, 2H), 7.311 (s, 1H), 7.192-7.139 (m, 1H), 6.591 (s, 1H), 2.161 (s, 3H), 1.675 (s, 6H).
Compound 1.15: 9.666 (s, 1H), 8.436-8.421 (d, 1H), 7.866-7.833 (d, 1H), 7.392-7.349 (m, 1H), 7.256-7.164 (m, 3H), 6.438 (s, 1H), 2.171 (s, 3H), 1.680 (s, 6H)?.
Compound 1.16: 9.722 (s, 1H), 8.428-8.407 (d, 1H), 7.855-7.822 (d, 1H), 7.379-7.324 (m, 3H), 7.264 (s, 1H), 6.651 (s, 1H), 2.130 (s, 3H), 1.649 (s, 6H).
Compound 1.17(CDCl+DMSO): 10.152 (s, 1H), 8.375-8.355 (d, 1H), 8.210 (s, 1H), 7.799-7.767 (d, 1H), 7.451-7.409 (m, 1H), 7.346-7.304 (m, 2H), 7.217 (s, 1H), 1.550 (s, 6H).
Compound 1.18: 9.469 (s, 1H), 8.512-8.493 (d, 1H), 7.938-7.906 (d, 1H), 7.434-7.370 (m, 2H), 7.034-7.297 (d, 1H), 7.239-7.232 (d, 1H), 7.214 (s, 1H), 1.735 (s, 6H).
Compound 1.19: 9.424 (s, 1H), 7.517-7.486 (m, 1H), 7.425-7.326 (m, 3H), 7.109-7.101 (d, 2H), 7.040 (s, 1H), 6.713 (s, 1H), 2.051 (s, 3H), 1.678 (s, 6H).
Compound 1.20: 9.459 (s, 1H), 7.519-7.487 (m, 1H), 7.435-7.273 (m, 5H), 7.051 (s, 1H), 6.602 (s, 1H), 2.083 (s, 3H), 1.688 (s, 6H).
Compound 1.21:9.011 (s, 1H), 7.528-7.497 (m, 1H), 7.388-7.271 (m, 5H), 7.167 (s, 1H), 7.025 (s, 1H), 2.175 (s, 3H), 1.621 (s, 6H).
Compound 1.24: 8.415 (br s, 1H), 8.234 (d, 1H), 7.915 (d, 1H), 7.518-7.310 (m, 5H), 7.310 (br s, 1H), 1.646 (s, 6H).
Compound 1.25a: 8.497-8.476 (q, 1H), 8.173-8.141 (q, 1H), 7.621-7.579 (q, 1H), 7. 405-7.390 (m, 3H), 7.281 (s, 1H), 2.192-2.094 (m, 4H), 1.402 (s, 3H), 1.027-1.004 (d, 3H), 0.884-0.863 (d, 3H).
Compound 1.25: 8.494-8.482 (d, 1H), 8.175-8.149 (d, 1H), 7.627-7.585 (m, 1H), 7.528 (s, 1H), 7.392 (s, 1H), 7.316 (s, 1H), 2.260-2.193 (m, 4H), 1.410 (s, 3H), 1.024-1.002 (d, 3H), 0.877-0.858 (d, 3H).
Compound 1.26: 9.784 (s, 1H), 8.441-8.421 (q, 1H), 7.862-7.831 (q, 1H), 7.404-7.353 (m, 3H), 7.216 (s, 1H), 6.396 (s, 1H), 2.271-2.188 (m, 1H), 2.166 (s, 3H), 1.562 (s, 3H), 1.110-1.087 (d, 3H), 1.019-0.996 (d, 3H).
Compound 1.27: 9.555 (s, 1H), 7.501-7.350 (m, 4H), 7.282-7.274 (m, 1H), 7.230-7.222 (d, 1H), 7.178 (s, 1H), 7.150-7.142 (d, 1H), 2.148-2.109 (m, 4H), 1.601 (s, 3H), 1.150-1.128 (d, 3H), 1.048-1.027 (d, 3H).
Compound 1.28: 9.688 (s, 1H), 8.446-8.425 (m, 1H), 7.865-7.832 (m, 1H), 7.389-7.346 (m, 1H), 7.234-7.228 (m, 1H), 7.181-7.163 (m, 2H), 6.541 (s, 1H), 2.458-2.414 (m, 2H), 2.169 (s, 3H), 2.045-1.977 (m, 2H), 1.878-1.748 (m, 4H).
Compound 1.29 (DMSO): 10.209 (s, 1H), 8.615 (s, 1H), 8.454-8.434 (m, 1H), 7.927-7.895 (m, 1H), 7.667 (s, 1H), 7.478-7.436 (m, 1H), 7.386-7.378 (d, 1H), 7.320 (s, 1H), 2.310-2.102 (m, 7H), 1.816-1.719 (m, 4H).
Compound 1.30: 9.725 (s, 1H), 8.435-8.420 (d, 1H), 7.863-7.831 (m, 1H), 7.389-7.346 (m, 1H), 7.260-7.150 (m, 3H), 6.471 (s, 1H), 2.400-2.318 (m, 2H), 2.164 (s, 3H), 1.706-1.452 (m, 8H).
Compound 1.31: 9.692 (s, 1H), 8.446-8.432 (d, 1H), 7.865-7.834 (m, 1H), 7.394-7.351 (m, 1H), 7.260-7.250 (m, 2H), 7.184 (s, 1H), 6.326 (s, 1H), 2.401-2.356 (m, 2H), 2.170 (s, 3H), 1.725-1.564 (m, 8H).
Compound 2.3: 7.327-7.319 (d, 1H), 7.275-7.271 (d, 1H), 6.251-6.227 (d, 1H), 5.049-4.999 (m, 1H), 2.148 (s, 3H), 1.685-1.660 (m, 3H).
Compound 2.4: 7.483-7.476 (d, 1H), 7.431-7.426 (d, 1H), 6.231-6.214 (d, 1H), 5.048-4.999 (m, 1H), 2.125 (s, 3H), 1.685-1.651 (m, 3H).
Compound 2.14: 7.429-7.423 (d, 1H), 7.381-7.379 (d, 1H), 6.145 (s, 1H), 2.097 (s, 3H), 1.809 (s, 6H).
Compound 2.22: 7.132-7.126 (d, 1H), 7.028 (d, 1H), 6.492 (s, 1H), 5.389 (s, 2H), 2.499-2.434 (m, 2H), 2.222-2.144 (m, 2H), 1.907-1.876 (m,4H).

The hydrogen atom in organic molecular can be replaced by methyl or other alkyl to improve the organic molecular’s liposolubility. The liposolubility is closely related to the transportation of organic molecules in insects, plants and other biological organisms. The suitable transportation of bioactive molecules plays an important role in the biological efficacy. The suitable transportation property of molecules is unpredictable, so it only can be obtained through extensively creative investigation.
The alkyl substituted acetonitrile benzamide compounds as shown in formula I in this invention possess surprisingly high insecticidal activity and fungicidal activity compared with known acetonitrile benzamide compounds. So, this invention also provides the use of the formula I compounds for protecting plant from insects and disease.
Another embodiment of this invention includes the fungicidal or insecticidal compositions, in which the compounds of formulas I are active ingredients. The weight percentage of active ingredient(s) in the compositions is from 1% to 99%. There are also carriers acceptable in agriculture, forestry or public health in these compositions.
The compositions of the present invention can be used in the form of various formulations. Usually, the compounds of formula I, the active ingredient, is diluted with an inert liquid or solid carrier to make a formulation such as a wettable powder or an emulsifiable concentrate etc., so that it can be easily dispersed as a fungicide or an insecticide. Therefore, in these compositions, at least a liquid or solid carrier is added, and usually suitable surfactant(s) can be added when needed.
Still also provided by this invention is the application method of controlling insects, which is to apply the compositions of the present invention to the growing loci of the insects as mentioned above. The suitably effective dosage of the compounds of the present invention is usually within a range of 10 g/ha to 1000 kg/ha, preferably from 20 g/ha to 500 g/ha.
Also provided by this invention is the application method of controlling diseases, which is to apply the compositions of the present invention to the growing loci of the diseases as above mentioned. The suitably effective dosage of the compounds of the present invention is usually within a range of from 100 g/ha to 2000 g/ha, preferably from 200 g/ha to 1000 g/ha.
For some applications, one or more other fungicides, insecticides, herbicides, plant growth regulators, or fertilizer can be added into the fungicidal or insecticidal compositions of the present invention to make additional merits and effects.
It shall be noted that variations and changes are permitted within the claimed scopes in the present invention.

DESCRIPTION OF THE INVENTION IN DETAIL
The following synthesis examples and results of biological tests are used to further illustrate the present invention, but not to limit it.

SYNTHSIS EXAMPLES
EXAMPLE 1: SYNTHSIS OF COMPOUND 1.2
(1) Synthesis of 2-aminopropanenitrile:

To a 500 mL flask sodium cyanide (4.95 g, 100 mmol) and ammonia hydrate (60 mL) were added. After sodium cyanide was solved completely, acetaldehyde (11.00 g, 100 mmol) and ammonium chloride (5.38 g, 100 mmol) were added. The reaction mixture was stirred for 48 hours at room temperature. Then dichloromethane was added to extract for 3 times (50 mL, 10 mL, 10 mL). The combined organic layers were dried over anhydrous magnesium sulfate and concentrated under vacuum to give the product (2.57 g) as a light green oil in 32% yield.
(2) Synthesis of 3-methyl-2-nitrobenzoyl chloride:

To a 500 mL flask 3-methyl-2-nitrobenzoic acid (20.0g, 110 mmol), 100 mL dichloromethane and oxalyl dichloride (21.0g, 165 mmol) were added. After five drops of N, N-dimethyl formamide were added, a large number of gas was released. After stirring for 8 hours at room temperature, the reaction mixture was concentrated under vacuum. Then 100 mL toluene was added, and the reaction mixture was concentrated again to give the product (22g) as a white solid in 100% yield.

(3) Synthesis of N-(1-cyanoethyl)-3-methyl-2-nitrobenzamide:

To a 500 mL flask 3-methyl-2-nitrobenzoyl chloride (21 g, 105 mmol), 200 mL dichloromethane and 2-aminopropanenitrile (7.0 g, 100 mmol) were added sequentially. To the mixture triethylamine (12.0 g, 120 mmol) was added dropwise and the reaction mixture was stirred for 3 hours at room temperature. Then the mixture was poured into 200 mL water and extracted with ethyl acetate (3×100 mL). The combined organic layers were washed with saturated sodium carbonate solution and brine, dried over anhydrous magnesium sulfate and concentrated to give 21.5 g dark brown oil. After separation through silica gel column chromatography (fluent: ethyl acetate/petroleum ether=1:1), 18.5 g orange solid was gained in 75% yield.
1H NMR (300MHz, CDCl3+CD3OD): 9.025-9.001 (d, 1H), 7.520-7.439 (m, 3H), 5.044-4.972 (m, 1H), 2.409 (s, 3H), 1.632-1.608 (d, 3H).

(4) Synthesis of 2-amino-N-(1-cyanoethyl)-3-methylbenzamide (Compound 2.1):

To a 250 mL flask N-(1-cyanoethyl)-3-methyl-2-nitrobenzamide (4.0 g, 17.2 mmol), tetrahydrofuran (40 mL), water (40 mL) and zinc powder (5.6 g, 86 mmol) were added sequentially. Concentrated hydrochloric acid (5.2 g, 51.6 mmol) was added dropwise to the mixture over the period of 30 minutes at room temperature. The reaction temperature was controlled under 30?. The reaction mixture was continued to react for 3 hours at room temperature. The insoluble substances were removed by filtration. The filtrate was extracted with ethyl acetate (2×100 mL). The combined organic extracts were washed with water, saturated sodium carbonate solution and brine, dried over anhydrous magnesium sulfate and concentrated to give the product (2.8 g) as a light yellow solid in 80% yield.

1H NMR (300MHz, CDCl3): 7.246-7.220 (d, 1H), 7.160-7.137 (d, 1H), 6.667-6.641 (d, 1H), 6.591-6.541 (t, 1H), 5.659 (s, 2H), 5.048-4.997 (m, 1H), 2.144 (s, 3H), 1.633-1.608 (d, 3H).

(5) Synthesis of 2-amino-5-chloro-N-(1-cyanoethyl)-3-methylbenzamide (Compound 2.2):

To a 50 mL flask 2-amino-N-(1-cyanoethyl)-3-methylbenzamide (1.8 g, 8.9 mmol) N-chloro succinimide (referred to as: NCS) (1.2 g, 8.9mmol) and dimethylformamide (20 mL) were added sequentially. The reaction mixture was stirred for 30 minutes at 100-110?. After being cooled down to room temperature, the reaction mixture was poured into 100 mL water and extracted with ethyl acetate (2×100 mL).The organic extracts were washed with water, brine, and dried over anhydrous magnesium sulfate, concentrated to give the product (1.8 g) as light yellow solid in 86% yeild. The HPLC analysis showed that there were no significant impurities .
1H NMR (300MHz, CDCl3): 7.535 (s, 1H), 7.331-7.324 (d, 1H), 7.104-7.102 (d, 1H), 5.040-5.016 (m, 1H), 2.131 (s, 3H), 1.671-1.647 (d, 3H).

(6) Synthesis of 3-chloro-2-hydrazinylpyridine:

To a 1000 mL flask 2,3-dichloropyridine (74 g, 500mmol), 50% hydrazine (250 g, 2.5 mol) and dioxane (300 mL) were added sequentially. The temperature of the reaction mixture was heated to reflux for 20 hours. Then the reaction mixture was cooled down to room temperature overnight and white crystal was precipitated. The white crystal was isolated via filtration and dried to give the product (51 g) as a white solid in 71% yield.
1H NMR (300MHz, CDCl3): 8.113-8.092 (d, 1H), 7.493-7.463 (d, 1H), 6.672-6.630 (q, 1H), 6.237 (s, 1H), 3.905 (s, 2H).

(7) Synthesis of ethyl 2-(3-chloropyridin-2-yl)-5-oxopyrazolidine-3-carboxylate:

To a 1000 mL flask 300 mL anhydrous ethanol, sodium ethoxide (15.6 g, 0.229 mol) and 3-chloro-2-hydrazinylpyridine (30.0 g, 0.208mol) were added. The reaction mixture was heated to reflux for 5 minutes. Diethyl maleate (36.0 g, 0.250 mmol) was added dropwise and heated to reflux for 10 minutes. After being cooled to 65?, the reaction mixture was neutralized with glacial acetic acid (25.2 g, 0.420mol) and diluted with 300mL water. The reaction mixture was cooled down to room temperature, and the aprecipitate formed. The product was isolated via filtration, washed with 40% aqueous solution of ethanol (3 × 50 mL) and dried to give the product (26.3g) as an orange solid in 42% yield.
1H NMR (300MHz, DMSO): 8.289-8.269 (q, 1H), 7.956-7.190 (q, 1H), 7.231-7.190 (q, 1H), 4.862-4.816 (q, 1H), 4.236-4.165 (q, 2H), 2.967-2.879 (q, 1H), 2.396-2.336 (q, 1H), 1.250-1.202 (t, 3H).

(8) Synthesis of ethyl 3-chloro-1-(3-chloropyridin-2-yl)-4, 5-dihydro-1H-pyrazole-5-carboxylate:

To a 100 mL flask acetonitrile (65 mL), ethyl 2-(3-chloropyridin-2-yl)-5-oxopyrazolidine-3-carboxylate (6.5 g, 24 mmol) and phosphoryl chloride (4.4 g, 28.8 mmol) were added. The reaction mixture was heated to reflux for 2 hours. The reaction mixture was distilled to remove 30 mL solvent.The concentrated reaction mixture was added to the mixture of sodium carbonate (10.1 g, 120 mmol) and water (40 mL). The reaction mixture was stirred for 20 minutes until no more gas released. The reaction mixture was diluted with 100 mL dichloromethane and stirred for 50 minutes. The mixture was extracted with dichloromethane (3 × 100 mL). The organic extracts were washed with water, dried over anhydrous magnesium sulfate and concentrated by rotary evaporator to give the product (4.7 g) as a dark amber oil in 68% yield.
1H NMR (300MHz, DMSO): 8.129-8.108 (q, 1H), 7.866-7.834 (q, 1H), 7.017-6.975 (q, 1H), 5.275-5.207 (q, 1H), 4.150-4.078 (q, 2H), 3.648-3.504 (m, 1H), 3.298-3.211 (m, 1H), 1.174-1.127 (t, 3H).

(9) Synthesis of ethyl 3-chloro-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylate:

To a 100 mL flask ethyl 3-chloro-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate (4.0 g, 13.9 mmol), acetonitrile (10 mL) and 98% sulfuric acid (2.8 g, 27.8mmol) were added. The reaction mixture was stirred for a few minutes. Then the potassium persulfate (6.0 g, 22.2mmol) was added. The reaction mixture was heated to reflux for 5 hours. The resulting orange slurry was filtered while still warm (50-65?) to remove a white precipitate. The filter cake was washed with acetonitrile (10 mL). The filtrate was concentrated to about 10 mL on rotary evaporator. Then 50 mL water was added. The solid product was removed by filtration, washed with 25% aqueous solution of acetonitrile (3 × 15 mL) and dried to give the product (3.2 g) as an orange solid in 80% yield.
1H NMR (300MHz, DMSO): 8.521-8.500 (d, 1H), 7.963-7.930 (d, 1H), 7.511-7.469 (q, 1H), 6.950 (s, 1H), 4.258-4.187 (q, 2H), 1.242-1.195 (t, 3H).

(10) Synthesis of 3-chloro-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid:

To a 100 mL flask ethyl 3-chloro-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylate (1.8 g, 6.3 mmol) and methanol (10 mL), water (10 mL) and sodium hydroxide (0.3 g, 6.9 mmol) were added. After being strried for 1 hour at room temperature, all of the starting materials had dissolved. The reaction mixture was concentrated to about 10 mL dark brown solution by rotary evaporator. Then 40 mL water was added. The aqueous solution was extracted with ethyl ether (50 mL) and acidified with concentrated hydrochloric acid to pH=4. The solid product was isolated via filtration, washed with 2 × 50 mL water and dried to give the product (1.4 g) as a white solid in 88% yield.
1H NMR (300MHz, DMSO): 8.578-8.566 (d, 1H), 8.278-8.251 (d, 1H), 7.719-7.677 (q, 1H), 7.234 (s, 1H).

(11) Synthesis of 3-chloro-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carbonyl chloride:

To a 100 mL flask 3-chloro-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid (15.0 g, 58.1 mmol), dichloromethane (100 mL) and oxalyl dichloride (11.1 g, 87.2 mmol) were added. After five drops of N, N-dimethyl formamide was added, a large number of gas was released. After being stirred for 8 hours at room temperature, the reaction mixture was evaporated to dryness at reduced pressure. Then 100 mL toluene was added, and the reaction mixture was concentrated again under vacuum to give the the product (16 g) as a green solid in 100% yield.

(12) Synthesis of compound 1.2:

To a 100 mL flask 2-amino-5-chloro-N-(1-cyanoethyl)-3-methylbenzamide (2.0 g, 8.4 mmol), dichloromethane (20 mL), 3-chloro-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carbonyl chloride (2.8 g, 10.1 mmol) and triethylamine (1.1 g, 10.9 mmol) were added. The reaction mixture was stirred for 3 hours at room temperature .Then the reaction mixture was poured into100 mL of water, extracted with ethyl acetate (2×100 mL). The organic extracts were washed with saturated sodium carbonate solution and brine, dried over anhydrous magnesium sulfate and concentrated by rotary evaporator. The residue was purified by chromatography on silica gel column chromatography (fluent: ethyl acetate/petroleum ether=1/2) to give the compound 1.2 (2.3 g) as a white solid in 58% yield.

EXAMPLE 2: SYNTHSIS OF COMPOUND 1.14
(1) Synthesis of 2-amino-2-methylpropanenitrile:

To a 250 mL flask sodium cyanide (4.95 g, 100 mmol) and ammonia hydrate (60 mL) were added. After being stirred at room temperature, sodium cyanide has dissolved completely, acetone (5.84 g, 100 mmol) and ammonium chloride (5.38 g, 100 mmol) were added. The reaction mixture was reacting for 48 hours at room temperature. The reaction mixture was extracted with dichloromethane for 3 times (50 mL, 10 mL, 10 mL). The combined organic extracts were dried over anhydrous magnesium sulfate and concentrated under vacuum to give the the product (5.25 g) as a colorless oil in 57% yield.

(2) Synthesis of N-(2-cyanopropan-2-yl) -3-methyl-2-nitrobenzamide:

To a 500 mL flask 3-methyl-2-nitrobenzoyl chloride (21.0 g, 105 mmol), dichloromethane (100 mL) and 2-amino-2-methylpropanenitrile (8.8 g, 105 mmol) were added sequentially. After triethylamine (12.6 g, 126 mmol) was added dropwise, the reaction mixture was stirred for 3 hours at room temperature. Then the reaction mixture was poured into 200 mL water, extracted with ethyl acetate (3×100 mL). The combined organic extracts were washed with saturated sodium carbonate solution and brine, dried over anhydrous magnesium sulfate, and concentrated to give the the product (19.2 g) as a white solid in 74% yield.

(3) Synthesis of 2-amino-N-(2-cyanopropan-2-yl)-3-methylbenzamide (Compound 2.11):

To a 250 mL flask N-(2-cyanopropan-2-yl)-3-methyl-2-nitrobenzamide (6.4 g, 25.9 mmol), acetic acid (80 mL) and iron powder (5.8 g, 103.6 mmol) were added sequentially. The reaction temperature was controlled under 80?. The reaction mixture was stirred for 3 hours. After being cooled down to room temperature, 100 mL water was added and the reaction solution was extracted with ethyl acetate (3×100 mL). The organic layer was washed with water and brine, dried over anhydrous magnesium sulfate, and concentrated to give the the product (4.5 g) as a brown yellow solid in 80% yield.

(4) Synthesis of 2-amino-5-chloro-N-(2-cyanopropan-2-yl)-3-methylbenzamide (Compound 2.12):

To a 150 mL flask 2-amino-N-(2-cyanopropan-2-yl)-3-methylbenzamide (4.3 g, 19.8 mmol), NCS (2.7g, 19.8 mmol) and dimethylformamide (50 mL) were added sequentially. The reaction mixture was stirred for 30 minutes at 100-110?. After being cooled down to room temperature, the reaction mixture was poured into 100 mL water and extracted with ethyl acetate (3×100 mL). The organic extracts were washed with water and brine, dried over anhydrous magnesium sulfate, and concentrated to give the product (4.0 g) as a black solid in 80% yield.
1H NMR (300MHz, CDCl3): 7.145-7.126 (m, 2H), 6.054 (s, 1H), 2.143 (s, 3H), 1.807 (s, 6H).

(5) Synthesis of ethyl 3-bromo-1-(3-chloropyridin-2-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate:

To a 150 mL flask acetonitrile (65 mL), ethyl 2-(3-chloropyridin-2-yl)-5-oxopyrazolidine-3-carboxylate (5.0 g, 18.5mmol) and phosphoryl bromide (3.4 g, 11.9 mmol) were added. The temperature of the reaction mixture was heated to reflux for 2 hours. The reaction mixture was distilled to remove 30 mL solvent and added to mixture of sodium carbonate (10.1 g, 120 mmol) and water (40 mL). The mixture was stirred for 20 minutes at which time gas evolution had ceased. The reaction mixture was diluted with dichloromethane (100 mL), stirred for 50 minutes and extracted with dichloromethane (3 × 100 mL). The organic extracts were washed with water, dried over anhydrous magnesium sulfate, and concentrated by rotary evaporator to give the product (6.0 g) as a amber oil in 97% yield.
1H NMR: 8.093-8.073 (q, 1H), 7.681-7.650 (q, 1H), 6.892-6.851 (q, 1H), 5.293-5.224 (q, 1H), 4.220-4.150 (q, 2H), 3.502-3.404 (q, 1H), 3.291-3.202 (q, 1H), 1.226-1.179 (t, 3H).

(6) Synthesis of ethyl 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylate:
:
To a 100 mL flask ethyl 3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxylate (4.0 g, 12.0 mmol), acetonitrile (10 mL) and 98% sulfuric acid (2.4 g, 24.0 mmol) were added. The mixture was stirred for a few minutes, and potassium persulfate (5.2 g, 19.2mmol) was added. The reaction mixture was heated to reflux for 5 hours. The resulting orange slurry while still warm (50-65?) was filtered to remove a white precipitat. Filter cake was washed by acetonitrile (10 mL). The filtrate was concentrated to about 10 mL on rotary evaporator. Then water (50 mL) was added. The solid product was isolated by filtration, washed with 25% aqueous solution of acetonitrile (3 × 15 mL) and dried to give the product (3.8 g) as an orange solid in 95% yield.
1H NMR (300MHz, CDCl): 8.522-8.501 (q, 1H), 7.927-7.895 (q, 1H), 7.465-7.424 (q, 1H), 7.034 (s, 1H), 4.262-4.190 (q, 2H), 1.240-1.192 (t, 3H).

(7) Synthesis of ethyl 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid:

To a 100 mL flask ethyl 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylate (1.4 g, 4.2mmol), methanol (10 mL), water (10 mL) and sodium hydroxide (0.2g, 4.6mmol) were added. The reaction mixture was stirred at room temperature for 1 hour, and all starting materials were dissolved. The reaction mixture was concentrated by rotary evaporator to about 10 mL dark brown solution. Then 40 mL water was added. Aqueous solution was extracted with ethyl ether (50 mL) and acidified with concentrated hydrochloric acid to pH=4. The solid product was isolated by filtration washed with water (2 × 50 mL) and dried to give the product (1.1 g) as a white solid in 85% yield.

(8) Synthesis of 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carbonyl chloride:

To a 100 mL flask 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid (0.9 g, 2.8 mmol), dichloromethane (10 mL) and oxalyl dichloride (0.7 g, 5.6 mmol) were added. After two drops of N,N-dimethyl formamide were added, a large number of gas was released. After stirring for 8 hours at room temperature, the reaction mixture was evaporated to dryness at reduced pressure. Then 50 mL toluene was added, and the reaction mixture was concentrated again under vacuum to give the product (0.9 g) as an oil in 100% yield.

(9) Synthesis of compound 1.14:

To a 100 mL flask 2-amino-5-chloro-N-(2-cyanopropan-2-yl)-3-methylbenzamide (0.64 g, 2.0mmol), dichloromethane (20 mL), 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carbonyl chloride (0.5 g, 2.0 mmol) and triethylamine (0.24 g, 2.4 mmol) were added. The reaction mixture was stirred for 3 hours at room temperature. Then reaction mixture was poured into water (100 mL), extracted with ethyl acetate (2×100 mL). The organic extracts were washed with saturated sodium carbonate solution and brine, dried over anhydrous magnesium sulfate and concentrated by rotary evaporator. The residue was purified by chromatography on silica gel column chromatography (fluent: ethyl acetate/petroleum ether=1/2) to give the compound 1.14 (0.4 g) as a white solid in 40% yield.

EXAMPLE 3: SYNTHSIS OF COMPOUND 1.17

To a 100 mL flask 2-amino-3,5-dichloro-N-(2-cyanopropan-2-yl)benzamide (0.51 g, 1.83 mmol) and dichloromethane (20 mL), 3-chloro-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carbonyl chloride (0.5 g, 1.83 mmol) and triethylamine (0.22 g, 2.2 mmol) were added. The reaction mixture was stirred for 3 hours at room temperature .Then the reaction mixture was poured into water (100 mL), extracted with ethyl acetate (2×100 mL). The organic extracts were washed with saturated sodium carbonate solution and brine, dried over anhydrous magnesium sulfate and concentrated by rotary evaporator. The residue was purified by chromatography on silica gel column chromatography (fluent: ethyl acetate/petroleum ether=1/2) to give the compound 1.17 (0.35 g) as a white solid in 38% yield.

EXAMPLE 4: SYNTHSIS OF COMPOUND 1.19
(1) Synthesis of ethyl 2-(3-chlorophenyl)-5-oxopyrazolidine-3-carboxylate:

To a 1000 mL flask anhydrous ethanol (300 mL), sodium ethoxide (35.7 g, 0.525 mol) and (2-chlorophenyl) hydrazine (71.5 g, 0.500 mol) were added. The temperature of the reaction mixture was heated to reflux for 5 minutes. Diethyl maleate (82.8 g, 0.575 mmol) was added dropwise and the mixture was re-heated to reflux for 10 minutes. After cooling to 65?, the reaction mixture was neutralized with glacial acetic acid (57.6 g, 0.961 mol) and diluted with water (400 mL). After being cooled to room temperature, aprecipitate formed. The solid was isolated by filtration, washed with 40% aqueous solution of ethanol (3 × 50 mL) and dried to give the product (64 g) as a solid in 48% yield.
1H NMR (300MHz, DMSO): 10.129 (s, 1H), 7.418-7.392 (d, 1H), 7.311-7.265 (m, 2H), 7.129-7.072 (m, 1H), 4.385-4.317 (q, 1H), 4.239-4.167 (q, 2H), 3.040-2.952 (q, 1H), 2.276-2.221 (q, 1H), 1.290-1.214 (t, 3H)?

(2) Synthesis of ethyl 3-chloro-1-(2-chlorophenyl)-4,5-dihydro-1H-pyrazole-5-carboxylate:

To a 100 mL flask acetonitrile (50 mL), ethyl 2-(2-chlorophenyl)-5-oxopyrazolidine-3-carboxylate (5.0 g, 16.7 mmol) and phosphoryl chloride (2.9 g, 16.7 mmol) were added. The reaction mixture was heated to reflux for 2 hours. The reaction mixture was distilled to remove 30 mL solvent and added to the mixture of sodium carbonate (10.1 g, 120 mmol) and water (40 mL). The mixture was stirred for 20 minutes at which time gas evolution had ceased. The reaction mixture was diluted with dichloromethane (100 mL), stirred for 50 minutes and extracted with dichloromethane (3 × 100 mL). The organic extracts were washed with water, dried over anhydrous magnesium sulfate and concentrated by rotary evaporator to give the product (2.8 g) as an oil in 58% yield.
1H NMR (300MHz, CDCl3): 7.437-7.404 (q, 1H), 7.336-7.304 (m, 1H), 7.243-7.187 (m, 1H), 7.079-7.023 (m, 1H), 5.314-5.262 (q, 1H), 3.992-3.920 (q, 2H), 3.544-3.449 (q, 1H), 3.357-3.285 (q, 1H), 1.008-0.961 (t, 3H).

(3) Synthesis of ethyl 3-chloro-1-(2-chlorophenyl)-1H-pyrazole-5-carboxylate:

To a 100 mL flask ethyl 3-chloro-1-(2-chlorophenyl)-4,5-dihydro-1H-pyrazole-5-carboxylate (2.8 g, 10.0 mmol), acetonitrile (30 mL) and 98% sulfuric acid (2.0 g, 20.0 mmol) were added. The mixture was stirred for a few minutes, and potassium persulfate (4.3g, 16.0mmol) was added. The reaction mixture was heated to reflux for 5 hours. The resulting orange slurry while still warm (50-65?) was filtered to remove the white precipitat. Filter cake was washed by acetonitrile (10 mL). The filtrate was concentrated to about 10 mL on rotary evaporator. Then water (50 mL) was added. The solid product was isolated by filtration, washed with 25% aqueous solution of acetonitrile (3 × 15 mL) and dried to give the product (1.6 g) as orange solid in 56% yield.
1H NMR (300MHz, DMSO): 7.528-7.438 (m, 4H), 6.930 (s, 1H), 4.177-4.132 (q, 2H), 1.207-1.159 (t, 3H).

(4) Synthesis of 3-chloro-1-(2-chlorophenyl)-1H-pyrazole-5-carboxylic acid:

To a 100 mL flask ethyl 3-chloro-1-(2-chlorophenyl)-1H-pyrazole-5-carboxylate (1.6 g, 5.6 mmol), methanol (10 mL), water (10 mL) and sodium hydroxide (0.27 g, 6.7 mmol) were added. The mixture was stirred at room temperature for 1 hour, and all starting materials were dissolved. The reaction mixture was concentrated to about 10 mL dark brown solution on rotary evaporator. Then 40 mL water was added. Aqueous solution was extracted with ethyl ether (50 mL) and acidified with concentrated hydrochloric acid to pH=4. The solid product was isolated by filtration, washed with water (2 × 50 mL) and dried to give the product (1.1 g) as a white solid in 79% yield.
1H NMR (300MHz, DMSO): 7.623-7.049 (m, 4H), 7.049 (s, 1H).

(5) Synthesis of 3-chloro-1-(2-chlorophenyl)-1H-pyrazole-5-carbonyl chloride:

To a 50 mL flask 3-chloro-1-(2-chlorophenyl)-1H-pyrazole-5-carboxylic acid (1.1 g, 4.3 mmol) and 20 mL dichloromethane and oxalyl dichloride (0.8 g, 6.4 mmol) were added. After one drop of N,N-dimethyl formamide was added, a large number of gas was released. After being stirred for 8 hours at room temperature, the reaction mixture was evaporated to dryness at reduced pressure. Then 20 mL toluene was added, and the reaction mixture was concentrated under vacuum to give the product (1.2 g) as an oil in 100% yield.

(6) Synthesis of compound 1.19:

To a 50 mL flask 2-amino-5-chloro-N-(2-cyanopropan-2-yl)-3-methylbenzamide (0.3 g, 1.2 mmol), dichloromethane (10 mL), 3-chloro-1-(2-chlorophenyl)-1H-pyrazole-5-carbonyl chloride (0.33 g, 1.2 mmol) and triethylamine (0.14 g, 1.4 mmol) were added. The reaction mixture was stirred for 3 hours at room temperature. Then reaction mixture was poured into water (50 mL), and extracted with ethyl acetate (2 × 50 mL). The organic extracts were washed with saturated sodium carbonate solution and brine, dried over anhydrous magnesium sulfate and concentrated by rotary evaporator. The residue was purified by chromatography on silica gel column chromatography (fluent: ethyl acetate/petroleum ether=1/2) to give the compound 1.19 (0.4 g) as a white solid in 68% yield.

EXAMPLE 5: SYNTHSIS OF COMPOUND 1.24
(1) Synthesis of N'-(2-chlorophenyl)-2,2,2-trifluoroacetohydrazide:

To a flask-3-neck (2-chlorophenyl) hydrazine (10.0 g, 70.4 mmol) and tetrahydrofuran (80 mL) were added sequentially. To the mixture 2,2,2-trifluoroacetic anhydride (14.6g, 70.4 mmol) in tetrahydrofuran (20 mL) was added dropwise, and the reaction mixture was reacted for 3 hours at room temperature . The reaction mixture was distilled to remove solvent and poured into 50 mL water, extracted with ethyl acetate (100 mL). The organic extracts were washed with 50 mL saturated sodium carbonate solution and 50 mL brine solution, dried over anhydrous magnesium sulfate, and evaporated to dryness at reduced pressure to give the product (15.7 g) as a yellow solid in 93% yield.
1H NMR (300MHz, CDCl3): 8.750 (br s, 1H), 7.306 (dd, 1H), 7.145 (dd, 1H), 6.947 (dd, 1H), 6.815 (dd, 1H), 6.590 (br s, 1H).

(2) Synthesis of (Z)-N'-(2-chlorophenyl)-2,2,2-trifluoroacetohydrazonic methanesulfonic anhydride:

To a flask-3-neck N'-(2-chlorophenyl)-2,2,2-trifluoroacetohydrazide (5.00 g, 29.1 mmol) and ethyl acetate (50 mL) were added sequentially. And methanesulfonyl chloride (3.8 g, 32.5 mmol) was added dropwise over a period of 30 minutes at 0?. After the reaction mixture was stirred for 30 minutes, triethylamine (4.11g, 40.6 mmol) were added dropwise and then white solid precipitated. The reaction mixture was stirred at room temperature until the reaction mixture reacted completely. The reaction mixture was poured into 50 mL water, extracted with 100 mL ethyl acetate. The organic extracts were washed with 50 mL brine, dried over anhydrous magnesium sulfate, and evaprorated to dryness at reduced pressure to give the product (4.2 g) as a viscous yellow solid in 59% yield.
1H NMR (300MHz, CDCl3): 8.854 (br s, 1H), 7.526 (dd, 1H), 7.327-7.231 (m, 2H), 6.944 (dd, 1H), 3.402 (s, 3H).

(3) Synthesis of ethyl 1-(2-chlorophenyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazole-5-carboxylate:

To a flask-3-neck the product of above step (2.00 g, 7.60 mmol), toluene (20 mL) and ethyl acrylate (1.53 g, 15.2 mmol) were added sequentially. And triethylamine (0.92 g, 9.14 mmol) was added dropwise over a period of 10 minutes at 0?. The reaction mixture was reacted at room temperature overnight until the reaction mixture reacted completely and the colour of the solution changed from yellow to brown. The reaction mixture was poured into 50 mL water, extracted with ethyl acetate (100 mL). The organic extracts were washed with 50 mL saturated sodium carbonate solution and 50 mL brine, dried over anhydrous magnesium sulfate, and evaprorated to dryness at reduced pressure. After separation through silica gel column chromatography, 0.8 g yellow oil was gained in 36% yield.
1H NMR(300MHz, CDCl3): 7.439 (br s, 1H), 7.349 (dd, 1H), 7.261 (dd, 1H), 7.118 (dd, 1H), 5.463 (dd, 1H), 3.966 (q, 2H), 3.449-3.384 (m, 2H), 0.993 (t, 3H).

(4) Synthesis of ethyl 1-(2-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylate:

To a flask-3-neck ethyl 1-(2-chlorophenyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazole-5-carboxylate (1.00 g, 3.48 mmol) and 10 mL tetrahydrofuran were added sequentially and N-chloro succinimide (0.51 g, 3.48 mmol) was added portionwise at room temperature. The reaction mixture was reacted at room temperature for 10 minutes and the colour of the solution changed from yellow to black. After 4 hours, the reaction mixture was poured into 50 mL water, extracted with ethyl acetate (100 mL). The organic extracts were washed with 50 mL saturated sodium carbonate solution and 50 mL brine, dried over anhydrous magnesium sulfate and evaprorated at reduced pressure. After separation through silica gel column chromatography, 0.6 g yellow oil was gained in 61% yield.
1H NMR (300MHz, CDCl3): 7.548-7.397 (m, 4H), 7.285 (s, 1H), 4.231 (q, 2H), 1.238 (t, 3H).

(5) Synthesis of 1-(2-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid:

To a single-neck-flask ethyl 1-(2-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylate (1.20 g, 3.72 mmol), tetrahydrofuran (10 mL) and 10 mL aqueous solution of sodium hydroxide (0.16 g, 3.72 mmol) were added sequentially. The reaction mixture was heated to 30?. The reaction mixture reacted until TLC (fluent: ethyl acetate/petroleum ether=1/1) showed that it reacted completely. The reaction mixture was poured into 50 mL water, extracted with 100 mL ethyl acetate. The aqueous layer was acidified with concentrated hydrochloric acid to pH=2-3 and extracted with 150 mL ethyl acetate. The organic extracts were washed with brine (3×50 mL), dried over anhydrous magnesium sulfate and concentrated to give the product (0.89 g) as a white solid in 82% yield.
1H NMR (300MHz, CDCl3): 7.543-7.418 (m, 4H), 7.348 (s, 1H).

(6) Synthesis of 1-(2-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carbonyl chloride:

To a single-neck-flask 1-(2-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid (0.40 g, 1.36 mmol), dichloromethane (10 mL) and oxalyl dichloride (0.34 g, 2.72 mmol) were added sequentially. The reaction mixture was stirred for 1 hour at room temperature and the gas bubbles became less. After one drop of N,N-dimethyl formamide was added, a large number of gas was released. The reaction mixture was stirred for 4-6 hours until there was no more gas bubbles to give off. When it reacted completely, the reaction mixture was evaprorated to dryness at reduced pressure. Then toluene was added, and the reaction mixture was concentrated under vacuum to give the product (0.6 g) as a yellow solid in 100% yield.

(7) Synthesis of compound 1.24:

To a 100 mL flask 2-amino-3,5-dichloro-N-(2-cyanopropan-2-yl)benzamide (0.52 g, 1.1 mmol), 20 mL dichloromethane and 1-(2-chlorophenyl)-3- trifluoromethyl-1H-pyrazole-5-carbonyl chloride (0.6 g, 1.1 mmol) and pyridine (0.15 g, 1.1 mmol) were added. The reaction mixture was stirred for 3 hours at room temperature. Then the reaction mixture was poured into 100 mL water, extracted with ethyl acetate (2×100 mL). The organic extracts were washed with saturated sodium carbonate solution and brine, dried over anhydrous magnesium sulfate and concentrated by rotary evaporator. The residue was purified by chromatography on silica gel column chromatography (fluent: ethyl acetate/petroleum ether=1/2) to give the compound 1.24 (0.4 g) as a white solid in 38% yield.

BIOLOGICAL TEST EXAMPLES
EXAMPLE 6 INSECTICIDAL ACTIVITY TESTS:

According to the solubility of test compounds, the original pesticides are dissolved in acetone or dimethyl sulfoxide, and then diluted with 1 ‰ solution of Tween 80 to the test liquid 50 ml, the content of acetone or dimethyl sulfoxide in the total solution is not more than 10%.
Exp. 6.1 Test against Diamondback moth (Plutella xylostella)
The cabbage leaves were perforated to get 1 cm diameter leaf discs by the hole puncher. Certain concentrations of test comopounds were sprayed on both sides of the discs at the spray volume of 0.5 mL by Airbrush spraying treatment. Ten test insects (2 years) were introduced on each treatment after drying. Each treatment repeated 3 times. The treated discs were placed in a chamber of 24?, 60%-70% relative humidity, no light. After 96 h, the number of surviving insects was investigated and the mortality rates were calculated.
In this test, the following compounds exhibite mortality 90% or more against diamondback moth at 150 ppm: 1.1?1.2?1.14a?1.14?1.25a?1.26.
The following compounds exhibite mortality 90% or more against diamondback moth at 40 ppm: 1.1?1.2?1.14a?1.26.
The following compounds exhibite mortality 90% or more against diamondback moth at 10 ppm: 1.1,1.14,1.16.
Exp. 6.2 Test against Beet armyworm (Laphygma exigua Hubner)
The cabbage leaves were perforated to get 1 cm diameter leaf discs by the hole puncher. Certain concentrations of test comopounds were sprayed on both sides of the discs at the spray volume of 0.5 ml by Airbrush. Ten test insects (3 years) were introduced on each treatment after drying. Each treatment repeated 3 times. The treated discs were placed in a chamber of 24?, 60%-70% relative humidity, no light. After 96 h, the number of surviving insects was investigated and the mortality rates were calculated.
In this test, the following compounds exhibite mortality 100% against Beet armyworm at 20 ppm: 1.23.
The following compounds exhibite mortality 90% or more against Beet armyworm at 1 ppm: 1.1?1.2?1.3?1.4?1.5?1.6?1.7?1.8?1.9?1.10?1.11? 1.14?1.15?1.16?1.17?1.18?1.19?1.20?1.21?1.24?1.27.
The following compounds exhibite mortality 90% or more against Beet armyworm at 0.2 ppm: 1.1?1.4?1.14?1.15?1.18?1.19?1.21?1.24.
According to above method, compound 1.14 and KC (compound D477 in the patent WO03/015518A1) were choosed to parallel test the activity against Beet armyworm. The result was listed in table 3.
Table 3: Parallel test result of compounds 1.14 and KC against Beet armyworm (mortality, %)

Concentration(ppm)
mortality
Compounds (%) 0.2 0.1
1.14 100 87.5
KC 87.5 50

The structure of compound KC is shown as follows:

KC
Exp. 7 Fungicidal activity tests
According to the solubility of test compounds, the original pesticides are dissolved in acetone or dimethyl sulfoxide, and then diluted with 1 ‰ solution of Tween 80 to the test liquid 50 ml, the content of acetone or dimethyl sulfoxide in the total solution is not more than 10%.
Exp. 7.1 In vitro fungicidal activity test against rice blast ( Pyricularia grisea).
The melt AEA culture medium was cooled to 60-70?, and calculated amount of the test compounds were added according to the designed concentration to prapare compound-containing culture medium, the final content of test compound was 25ppm, After the medium cooling down sufficiently, rice blast pathogen of 0.5 cm diameter was inoculated and placed into the growth oven. The evaluation was performed after 10 days of inoculation. The measurement of the diameter of each colony was carried out and the rate of fungi inhibition was calculated.
The control efficacies of compound 1.17 against rice blast is over 90%.

Exp. 7.2 In vivo fungicidal activity test against cucumber downy mildew:
Select a consistent growth of potted cucumber seedlings, neatly cut growing point and two mail leaves reserved. The testing compound solutions were sprayed at 400 ppm. Cucumber downy mildew spore suspension was inoculated at the second day after the treatment of the test materials, then placed in the artificial climate chamber (temperature: day 25 ?, the night 20 ?, relative humidity: 95 ~ 100%) to cultivate, investigating the prevention and control effect after 6 days of moisturizing cultivation, recorded the onset of disease in 6 levels, calculated prevention control effect according to disease index.
The protective controlling effect of compound 1.14 against cucumber downy mildew is more than 90%.

We Cliams

1. A benzamide compounds characterized as indicated by formula I:

I
Wherein:
R1 is H or C1-C6 alkyl;
R2 is H or C1-C6 alkyl;
R3 is C1-C6 alkyl or C3-C6 cycloalkyl, the hydrogen group on the all substituents can also be further substituted by the following groups: halogen, NO2, C1-C3 alkoxy, phenoxy, C1-C3 alkylthio, C1-C3 alkylsulfinyl or C1-C3 alkylsulfonyl;
Or R2 and R3 are connected to the same carbon together to form C3-C6 cycloalkyl;
R4 is H, halogen or CN;
R5 is halogen or C1-C3 alkyl;
R6 is halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy or C1-C3 haloalkoxy;
R7 is H, halogen, CN, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 alkylthio, C1-C3 alkylsulfinyl or C1-C3 alkylsulfonyl;
R8 is halogen, CN, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy or C1-C3 alkythio;
X is CH, CF, CCl or N.

2. The compounds according to the claim 1, characterized in that wherein:
R1 is H;
R2 is H or C1-C3 alkyl;
R3 is C1-C3 alkyl;
Or R2 and R3 are connected to the same carbon together to form C3-C6 cycloalkyl;
R4 is H, halogen or CN;
R5 is halogen or C1-C3 alkyl;
R6 is halogen or C1-C3 haloalkyl;
R7 is H, halogen, CN or C1-C3 haloalkyl;
R8 is halogen;
X is CH, CF, CCl or N.
3. The compounds according to the claim 2, characterized in that wherein:
R1 is H;
R2 is H or methyl;
R3 is methyl;
R4 is Cl, Br, I, or CN;
R5 is Cl, Br or methyl;
R6 is Cl, Br or CF3;
R7 is H, Cl or CF3;
R8 is Cl;
X is CH, CF, CCl or N.

4. An intermediate to prepare the compounds of claim 1 characterized as indicated by formula II:

II
Wherein:
R1 is H or C1-C6 alkyl;
R2 is H or C1-C6 alkyl;
R3 is C1-C6 alkyl or C3-C6 cycloalkyl, the hydrogen group on the all substituents can also be further substituted by the following groups: halogen, NO2, C1-C3 alkoxy, phenoxy, C1-C3 alkylthio, C1-C3 alkylsulfinyl or C1-C3 alkylsulfonyl;
Or R2 and R3 are connected to the same carbon together to form C3-C6 cycloalkyl;
R4 is H, halogen or CN;
R5 is halogen or C1-C3 alkyl.

5. The formula I compounds according to the claim1 are used to control insects.

6. The formula I compounds according to the claim1 are used to control diseases.

7. A fungicidal or insecticidal composition, characterized in that wherein: comprising the characterised compounds of formula I of the claim 1 and an acceptable carrier in agriculture, forestry or public health, in which the weight percentage of active ingredient(s) is 1%-99%.

8. A method for controlling insects, characterized in that wherein: applying the composition of claim 7 to pests or its growth medium with effective dosage within a range of from 10 g/ha to 1000 g/ha.

9. A method for controlling diseases, characterized in that wherein: applying the composition of claim 7 to diseases or its growth medium with effective dosage within a range of from 100 g/ha to 2000 g/ha.

10. A Benzamide Compounds And Applications Thereof is claimed substantially as herein described with forgoing description

Dated this 29th day of September 2009.

Documents:

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Patent Number

270640

Indian Patent Application Number

1808/MUMNP/2009

PG Journal Number

02/2016

Publication Date

08-Jan-2016

Grant Date

06-Jan-2016

Date of Filing

30-Sep-2009

Name of Patentee

SINOCHEM CORPORATION

Applicant Address

6-12F CENTRAL TOWER, CHEMSUNNY WORLD TRADE CENTER, 28 FUXINGMENNEI DAJIE, BEIJING 100045

Inventors:

#	Inventor's Name	Inventor's Address
1	LI BIN	8 SHENLIAODONG ROAD, TIEXI DISTRICT SHENYANG LIAONING 110021
2	XIANG DONG	8 SHENLIAODONG ROAD, TIEXI DISTRICT SHENYANG LIAONING 110021
3	CHAI BAOSHAN	8 SHENLIAODONG ROAD, TIEXI DISTRICT SHENYANG LIAONING 110021
4	YUAN JING	8 SHENLIAODONG ROAD, TIEXI DISTRICT SHENYANG LIAONING 110021
5	YANG HUIBIN	8 SHENLIAODONG ROAD, TIEXI DISTRICT SHENYANG LIAONING 110021
6	ZHANG HONG	8 SHENLIAODONG ROAD, TIEXI DISTRICT SHENYANG LIAONING 110021
7	WU HONGFEI	8 SHENLIAODONG ROAD, TIEXI DISTRICT SHENYANG LIAONING 110021
8	YU HAIBO	8 SHENLIAODONG ROAD, TIEXI DISTRICT SHENYANG LIAONING 110021

PCT International Classification Number

C07D 401/04,A01N 43/56,A01P3/00,A01P7/04

PCT International Application Number

PCT/CN2008/070830

PCT International Filing date

2008-04-28

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1	200810057102.1	2008-01-30	China
2	200710011176.7	2007-04-30	China