(en)The present invention discloses nitromethylene derivatives and the uses thereof. These derivatives are obtained by adding ring structure onto the known nitromethylene compounds, by which both their stability for light and their liposolubility are increased. Furthermore, by using the substituents linked to ether bond, the steric orientation of the nitro group and the liposolubility of the compounds are controlled. The insecticidal activity tests show that the compounds and their derivatives of the invention display high efficiency on killing various destructive insects with piercing-sucking type or scratching type mouthparts, such as aphid, leafhopper, plant hpooer, thrips and white fly.

1.ApplicationNumber: US-75183607-A
1.PublishNumber: US-2007281950-A1
2.Date Publish: 20071206
3.Inventor: QIAN XUHONG
LI ZHONG
TIAN ZHONGZHEN
HUANG QINGCHUN
FANG JICHAO
SONG GONGHUA

4.Inventor Harmonized: QIAN XUHONG(CN)
LI ZHONG(CN)
TIAN ZHONGZHEN(CN)
HUANG QINGCHUN(CN)
FANG JICHAO(CN)
SONG GONGHUA(CN)

5.Country: US
6.Claims:
(en)The present invention discloses nitromethylene derivatives and the uses thereof. These derivatives are obtained by adding ring structure onto the known nitromethylene compounds, by which both their stability for light and their liposolubility are increased. Furthermore, by using the substituents linked to ether bond, the steric orientation of the nitro group and the liposolubility of the compounds are controlled. The insecticidal activity tests show that the compounds and their derivatives of the invention display high efficiency on killing various destructive insects with piercing-sucking type or scratching type mouthparts, such as aphid, leafhopper, plant hpooer, thrips and white fly.

7.Description:
(en)CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a continuation of International application number PCT/CN2005/000617, filed Apr. 30, 2005 which claims priority to Chinese application No. CN 200410084457.1 filed Nov. 23, 2004, the contents of both are herein incorporated in their entirety by reference.


FIELD OF THE INVENTION
This invention relates to nitromethylene derivatives and the uses thereof.
BACKGROUND OF THE INVENTION
Alkaloid nicotine is a natural insecticide from the extraction of tobacco leaves, and it acts on the postsynaptic nicotinic acetylcholine receptor (nAchRs). By so far, using natural nicotine as a leading compound, researchers have been making efforts to look for and develop a new insecticidally active compound having a similar structure and the same mechanism of action as nicotine. Since Soloway et al firstly reported the insecticidally active nitromethylene heterocyclic compounds in 1978, researchers have been changing the functional groups of nitromethylene heterocyclic compounds and Bayer AG successfully developed the first nicotine insecticide—Imidacloprid in middle 1980s. Due to its unique mechanism of action, no mutual resistance with common insecticides, high effect, broad spectrum, good root systemic ability, contact toxicity, stomach toxicity, low toxicity to mammalian, and safety to the environment, this kind of nicotine insecticide catches people's attention at once. A series of nicotine insecticide such as Thiacloprid, Clothianidin, Thiamethoxam, Acetamiprid, Nitenpyram and Dinotefuran are developed (EP 247477, 296453, 685477, 235725, 235725, 315826, 192060, 244777, 0386565, 580553, 1031566,JP 62292765, 8259568, 8291171, 7242633).
Compared to Imidacloprid, nitromethylene compounds have higher binding affinity and insecticidal activity. Whereas its use as an insecticide has been restricted by its instability to light and low LogP value. Therefore, the technical problem to be solved by the present invention is how to structurally modify the highly active nitromethylene compound to make it useful as an insecticide.
SUMMARY OF THE INVENTION
The object of this invention is to provide a kind of nitromethylene derivatives and the uses thereof.
Based on the current nitromethylene compound, this invention adds a new ring to its structure in order to enhance its light stability and liposolubility. Furthermore, this invention can control the space orientation and liposolubility by the substituent linked to an ether bond.
According to the first aspect of this invention, it is provided a nitromethylene derivative of formula (I), or an agriculturally acceptable salt thereof.


wherein R 1 is a substituted or unsubstituted 5- or 6-membered heterocycle containing nitrogen, oxygen and/or sulfur, the substituents are one to three substituents selected from the group consisting of a halogen atom, C 1-4 haloalkyl and C 1-4 haloalkoxyl;

R 2 is a hydrogen atom, a saturated or unsaturated C 1-8 hydrocarbyl group, a saturated or unsaturated C 1-8 halogenated hydrocarbyl group, —CH 2 CH 2 OCH 2 CH 3 , —CH 2 CH 2 OCH 3 , a substituted or unsubstituted phenyl group, a substituted or unsubstituted benzyl group, a substituted or unsubstituted C 1-8 alkoxyl group which may be saturated or unsaturated, wherein the substituents are one to three substituents selected from the group consisting of a halogen atom, C 1-4 haloalkyl and C 1-4 haloalkoxyl;
or R 2 is a group of the following formula:


wherein Ra is methyl, trifluoromethyl or phenyl; Rb is methyl, trifluoromethyl, pyridyl, phenyl or phenyl substituted by a halogen atom and/or a nitro group;
R 3 and R 4 independently is hydrogen, a substituted or unsubstituted C 1-3 alkyl group, wherein the substituents are one to three substituents selected from the group consisting of halogen, C 1-4 haloalkyl and C 1-4 haloalkoxyl;
A is O, S or N;
n is 0 or 1.
Preferably, R 1 is one of pyridyl, thiazolyl, pyrimidinyl, tetrahydrofuryl, oxazolyl, or halide thereof (especially chloride); R 2 is saturated or unsaturated C 1-8 hydrocarbyl, saturated or unsaturated C 1-8 halogenated hydrocarbyl, —CH 2 CH 2 OCH 2 CH 3 , —CH 2 CH 2 OCH 3 , a saturated or unsaturated C 1-8 alkoxyl group; R 3 is hydrogen or methyl; R 4 is hydrogen or C 1-3 alkyl group.
One kind of especially preferable compound has the structure of formula II (i.e. R 3 =R 4 =H, n=0):


wherein R 1 , R 2 and A are defined as above.
More preferably, R 1 represents


More preferably, R 2 is saturated or unsaturated C 1-5 hydrocarbyl group, a saturated or unsaturated C 1-5 hydrocarbyl group which may be substituted by halogen (such as fluorine or chlorine), —CH 2 CH 2 OCH 2 CH 3 , —CH 2 CH 2 OCH 3 , saturated or unsaturated C 1-8 alkoxyl group.
More preferably, A is O or S.
According to the second aspect of this invention, it is provided the use of the nitromethylene derivatives or the salts thereof to prepare chemical insecticide for agriculture.
According to the third aspect of this invention, it is provided an insecticidal composition comprising an effective amount of the compound of the present invention or an agriculturally acceptable salt thereof in mixture with an agriculturally acceptable carrier or diluent.
The nitromethylene derivatives can be synthesized by the following scheme:


In one of the preferable example, the ether derivatives containing a nitromethylene structure can be prepared by the following steps:
(1): A mixture of nitromethane and carbon bisulfide dissolved in alcohols is added dropwise to the solution of potassium hydroxide in alcohol at room temperature. The reaction is carried out at the temperature range of 0-35° C. for 2-10 hours. The solid is filtered out to afford a crude product potassium 2-nitroethene-1,1-bis(thiolate) which is a brown yellow powder.
(2): Potassium 2-nitroethene-1,1-bis(thiolate) is dissolved in alcohol, and then to the resulting mixture is added dropwise dimethyl sulfate solution. The reaction is stirred at room temperature for 2-8 hours. The mixture is filtrated to obtain crude product 1,1 -dimethylthio-2-nitroethene, which is a light brown yellow powder.
(3): The solution of 2-chloro-5-(chloromethyl)pyridine in acetonitrile is added dropwise to 5-10 mole of diamine solution. The reaction is carried out at the temperature range of 0-50° C. for 5-10 hours. The mixture is distillated under reduced pressure to remove diamine, and then dissolved in ethyl acetate and evaporated to obtain N 1 -((6-chloropyridin-3-yl)methyl)diamine
(4): The mixture of N 1 -((6-chloropyridin-3-yl)methyl) diamine and 1,1-dimethylthio-2-nitroethene is dissolved in ethanol and refluxed for 4-8 hours to obtain the product nitromethylene compound.
(5): In the presence of a acid catalyst such as hydrochloric acid, sulfuric acid, acetic acid, trifluoroacetic acid and the like, nitromethylene compound reacts with acraldehyde to obtain a new nitromethylene compound having hydroxyl.
In the presence of a catalytic amount of acid catalyst such as hydrochloric acid, sulfuiric acid, acetic acid, trifluoroacetic acid and the like, the mixture of the new nitromethylene compound having hydroxyl and various alcohols is refluxed to obtain the target compound.
In the presence of a catalytic amount of acid catalyst such as Lewis acid, such as trifluoroboric acid, aluminum trichloride, and the like, the mixture of the new nitromethylene compound having a hydroxyl and various mercaptans is refluxed to obtain the target compound.
In the presence of an acid-binding agent such as organic or inorganic alkali, for example pyridine, triethylamine, potassium carbonate, potassium hydroxide and the like, the mixture of the new nitromethylene compound having hydroxyl and various acyl chlorides is refluxed to obtain the target compound.
In another preferable example, the Schiff's base derivatives of nitromethylene compound can be prepared by the following steps:
(1) The mixture of nitromethylene compound and methyl acrylate reacts at 0-100° C. to obtain a new nitromethylene compound bearing carbonyl group;
(2) The mixture of the new nitromethylene compound with carbonyl group and hydroxylamine is refluxed to obtain new Schiffs base derivatives of nitromethylene compound
The Schiff's base derivatives of nitromethylene compound can react with halogen substituted alkanes to obtain the target compound in the presence of organic or inorganic alkali such as sodium hydride, sodium methoxide, sodium ethoxide, potassium hydroxide and the like.
The Schiff's base derivatives of nitromethylene compound can react with various acyl chlorides to obtain the target compound in the presence of an acid-binding agent such as organic or inorganic alkali, for example pyridine, triethylamine, potassium carbonate, and the like.
The invention is further illustrated by the following examples. It should be appreciated that these examples are only intended to illustrate the invention, but not to limit the scope of the invention. For the experimental methods in the following examples, they are performed under routine conditions, or as instructed by the manufacturers, unless otherwise specified.


EXAMPLE 1
Synthesis of 1-((6-chloropyridin-3-yl)methyl)-8-nitro-1,2,3,5,6,7-hexahydro imidazo[1,2-a]pyridin-5-ol (compound 1)
(1) Synthesis of potassium 2-nitro-ethene-1,1-bis(thiolate)









4 g (0.03 mol) of nitromethane and 6 ml (0.05 mol) of carbon bisulfide were placed in a 100 ml three-necked flask and 10 ml of ethanol was added as a solvent, and then the solution was stirred. To the resulting solution was added slowly and dropwise the solution of 8 g (0.14 mol) of potassium hydroxide in 40 ml of ethanol at room temperature over nearly 30 min. Since the reaction was exothermic, the rate of addition depended on the reaction temperature which was preferably between 30-35° C. After the addition was complete, the mixture was further stirred for 2 hours, filtered to obtain a crude product, which was a brown yellow powder in 72% yield.
(2): Synthesis of 1,1-dimethylthio-2-nitroethene


To a solution of 2 g (0.0094 mol) of potassium 2-nitroethene-1,1-bis(thiolate) in 10 ml of dried methanol, 0.0187 mol of dimethyl sulphate was added. The mixture was then stirred for 2 hours at room temperature. The precipitated solid was filtered to obtain crude product, which was a light brown yellow powder in 70% yield.
GC/ MS(m/s) 165 (31) M + ,148(17), 104(66), 86(100), 72(93), 57(20).
(3): Synthesis of N 1 -((6-chloropyridin-3-yl)methyl)ethane-1,2-diamine


To a stirred solution of 4.2 g (0.03 mol) of potassium carbonate and 10 ml (0.15 mol) of ethylenediamine in a 50 ml of flask placed in an ice bath, 4.8 g (0.03mol) of 2-chloro-5-(chloromethyl)pyridine dissolved in 15 ml of acetonitrile was added dropwise and slowly for nearly 20 min. After addition, the ice bath was removed and then the mixture was stirred for 8 hours at room temperature. After the reaction was stopped, a large amount of water was added to dissolve potassium carbonate and ethylenediamine, and the mixture was extracted with dichlormethane. The lower organic phase was collected, dried, and evaporated to dryness (It was better to remove all of the ethylenediamine in the solvent since its presence would influence the following step). The obtained product was yellow oily liquid in 68% yield.
GC MS(m/s) 185 (5) M + , 155(49), 126(100), 99(9), 90(12).
(4): Synthesis of 2-chloro-5-((2-(nitromethylene)imidazolidin-1-yl)methyl) pyridine


2.5 g (0.0178 mol) of 1,1-dimethylthio-2-nitroethene, 3.3g (0.0178 mol) of N 1 -((6-chloropyridin-3-yl)methyl)ethane-1,2-diamine were added to 15 ml of ethanol. The resulting mixture was heated under reflux for 4 hours at 80-90° C. The mixture was then cooled to educe solid, concentrated, filtrated and dried to give a light yellow powder in 56% yield.
R f =0.46 (petroleum ether: ethyl acetate =1:1).
Mp=156.9° C.-161.8° C. GC MS (m/s) 220 (25), 126(100), 90(9).
(5): Synthesis of 1-((6-chloropyridin-3-yl)methyl)-8-nitro-1,2,3,5,6,7-hexahydro imidazo[1,2-a]pyridin-5-ol


A mixture of 0.509 g (0.002 mol) of 2-chloro-5-((2-(nitromethylene)imidazolidin-1-yl)methyl)pyridine, 15 ml of anhydrous acetonitrile, 0.15 ml of acrylaldehyde and a catalytic amount of HCl place in a 50 ml of flask was heated to 40° C. and the mixture was kept at 40° C. and stirred for 12 hours. After the reaction was stopped, the precipitated solid was filtrated to give a crude product. After recrystallization, the pure product was a yellow powder in 40% yield.
Mp=169.0-172.1° C.
IR (KBr, cm −1 ) 3190, 1560, 1520, 1370, 1300, 1150, 970, 590.
1 HNMR (CDCl 3 ), δ (ppm)500 MHz: 8.37(d, J=2 Hz, 1H, Py-H), 7.85(dd, J 1 =2 Hz, J 2 =8.29 Hz, 1H, Py-H), 7.41(d, J=8 Hz, 1H, Py-H), 6.33(d, J=5.47 Hz, 1H, —OH), 4.86(m, 1H, —CHOH), 4.65(dd, J 1 =J 2 =15 Hz, 2H, —CH 2 -N—), 3.52(m, 4H, imidazolidine-H), 2.60(m, 2H, —CH 2 CH 2 —), 1.79(m, 2H, —CH 2 CH 2 —).
GC MS (m/s) 220 (25), 126(100), 90(9).
Elementary analysis Calculated: C 50.25, H 4.87, N 18.03; found C 50.12, H 4.82, N 18.31
EXAMPLE 2
Synthesis of 1-((6-chloropyridin-3-yl)methyl)-5-methoxy-8-nitro-1,2,3,5,6,7-hexahydroimidazo[1,2-a]pyridine (compound 2)









0.31 g (0.0001 mol) of compound 1 was added to a 50 ml of round-bottomed flask, and 15 ml of methanol and a catalytic amount of glacial acetic acid were added. The resulting mixture was refluxed and followed by TLC. After the reaction was stopped, the solvent was removed. The residue was then separated to give a pure yellow powder by column chromatography in 90% yield.
Mp=154.0-155.4° C.
IR (KBr, cm −1 ) 2900, 1560, 1350, 1080, 900, 760, 590
1 H NMR (CDCl 3 ), δ (ppm) 500 MHz: 8.32(d, J=2 Hz, 1H, Py-H), 7.88(dd, J 1 =2 Hz, J 2 =8 Hz, 1H, Py-H), 7.35(d, J=8 Hz, 1H, Py-H), 4.78(d, J 1 =15 Hz, J 2 =15 Hz, 2—CH 2 —N—), 4.48(t, J 1 =3 Hz,J 2 =3 Hz, 1H, —CHO—), 3.60(m, 4H, imidazolidine-H), 3.19(m, 3H, —OCH 3 ), 2.90(m, 2H, —CH 2 CH 2 —), 1.95(m, 2H, —CH 2 CH 2 —)
Elementary analysis Calculated: C 51.78, H 5.28, N 17.25; found C 51.95, H 5.12, N 17.04
EXAMPLE 3
Synthesis of 1-((6-chloropyridin-3-yl)methyl)-5-ethoxy-8-nitro-1,2,3,5,6,7-hexahydroimidazo[1,2-a]pyridine(compound 3)









Following the steps described in example 2, except that ethanol was used instead of methanol, a pure yellow powder was obtained by column chromatography in 85% yield.
Mp=126.4-128.1° C. IR (KBr) 3050 m, 2870 m, 1570 vs, 1500s, 1310 vs, 1150vs, 1030s, 970 m, 760 m, 580 m cm −1 1 H NMR (CDCl 3 ) δ (ppm) 500 MHz=8.33(d, J=2 Hz, 1H, Py-H), 7.91(dd, J 1 =2 Hz, J 2 =2 Hz, 1H, Py-H), 7.33(d, J=8 Hz, 1H, Py-H), 4.78(d, J 1 =15 Hz, J 2 =15 Hz, 2H, —CH 2 —N—), 4.54(t, J 1 =3 Hz, J 2 =3 Hz, 1H, —CHO—), 3.68(m, 2H, —O—CH 2 —), 3.57(m, 4H, imidazolidine-H), 2.87 (m, 2H, —CH 2 CH 2 —), 1.89(m, 2H, —CH 2 CH 2 —), 1.23(t, J 1 =7 Hz, J 2 =7 Hz, 3H, —CH 3 )
Elementary analysis Calculated: C 53.18, H 5.65, N 17.54; found C 53.64,H 5.57, N 17.68
EXAMPLE 4
Synthesis of 1-((6-chloropyridin-3-yl)methyl)-5-propoxy-8-nitro- 1,2,3,5,6,7-hexahydroimidazo[1,2-a]pyridine (compound 4)









Following the steps described in example 2, except that propanol was used instead of methanol, a pure yellow powder was obtained by column chromatography in 78% yield.
Mp=115.71-117.6° C.
IR (KBr cm −1 ) 2900, 2370, 1580, 1500, 1310, 1150, 1090, 1000, 820
1 H NMR (CDCl 3 ) δ (ppm) 500 MHz : 8.37(d, J=2 Hz, 1H, Py-H), 7.89(dd, J 1 =2 Hz, J 2 =2 Hz, 1H, Py-H), 7.32(d, J=8 Hz, 1H, Py-H), 4.77(d, J 1 =15 Hz, J 2 =15 Hz, 2H,—CH 2 —N—), 4.56(t, J 1 =3 Hz, J 2 =3 Hz, 1H, —CHO—), 3.68(m, 2H, —O—CH 2 —), 3.57(m, 4H, imidazolidine-H), 2.84 (m, 2H, —CH 2 CH 2 —), 1.89(m, 2H, —CH 2 CH 2 —), 1.68(m, 2H, —CH 2 CH 3 ), 0.93(t,3H,—CH 3 )
Elementary analysis Calculated: C 54.47, H 6.00, N 15.88; found C 54.62, H 5.98, N 15.54
EXAMPLE 5
Synthesis of 1-((6-chloropyridin-3-yl)methyl)-5-isopropoxy-8-nitro-1,2,3,5,6,7-hexahydroimidazo[1,2-a]pyridine (compound 5)









Following the steps described in example 2, except that propan-2-ol was used instead of methanol, a pure yellow powder was obtained by column chromatography in 80% yield.
Mp=129.9-134.6 ° C.
IR (KBr cm −1 ) 2900, 2370, 1560, 1330, 1200, 1120, 1070, 1000, 970, 820, 590
1 H NMR (CDCl 3 ) δ (ppm) 500 MHz: 8.32(d, J=2 Hz, 1H, Py-H), 7.91(dd,J 1 =2 Hz, J 2 =2 Hz, 1H, Py-H), 7.31(d, J=8 Hz, 1H, Py-H), 4.76(d, J 1 =15 Hz,J 2 =15 Hz, 2H, —CH 2 —N—), 4.59(t, J 1 =3 Hz, J 2 =3 Hz, 1H, ——CHO—), 3.72 (m, 2H, —O—CH—), 3.69(m, 4H, imidazolidine-H), 2.89(m, 2H, —CH 2 CH2—), 1.87(m, 2H, —CH 2 CH 2 —), 1.21(m, 6H, —(CH 3 ) 2 )
Elementary analysis Calculated: C 54.47, H 6.00, N 15.88; found C 54.52, H 5.84, N 15.90
EXAMPLE 6
Synthesis of 1-((6-chloropyridin-3-yl)methyl)-8-nitro-5-pentyloxy-1,2,3,5,6,7-hexahydroimidazo[1,2-a]pyridine (compound 6)









Following the steps described in example 2, except that pentanol was used instead of methanol, a pure yellow powder was obtained by column chromatography in 75% yield.
Mp=83.5-85.2° C.
IR (KBr cm −1 )2900, 2720, 1670, 1550, 1440, 1330, 1150, 1080, 980, 810, 750, 590
1 H NMR (CDCl 3 ) δ (ppm) 500 MHz : 8.33(d, J=2 Hz, 1H, Py-H), 7.92(dd, J 1 =2 Hz, J 2 =8 Hz, 1H, Py-H), 7.31(d J=8 Hz, 1H, Py-H), 4.77(d, J 1 =15 Hz, J 2 =15 Hz, 2H, —CH2—N—), 4.59(s, 1H, —CHO—), 3.68(m, 2H, —O—CH2—), 3.51(m, 4 H, imidazolidine-H), 2.86(m, 2H, —CH2CH2—), 1.95(m, 2H, —CH2CH2—), 1.58(m, 2H, —O—(CH2)3—), 1.32(m, 4H, —O—(CH2)3—), 0.92(t,3H,—CH3)
Elementary analysis Calculated: C 57.76, H 6.62, N 14.71; found C 57.68, H 6.45, N 14.42
EXAMPLE 7
Synthesis of 5-(2-chloroethoxy)- 1 -((6-chloropyridin-3 -yl)methyl)-8-nitro-1,2,3,5,6,7-hexahydroimidazo[1,2-a]pyridine (compound 7)









Following the steps described in example 2, except that 2-chloroethanol was used instead of methanol, a pure yellow powder was obtained by column chromatography in 79% yield.
Mp=158.5-159.4° C.
IR (KBr cm −1 ) 3000, 2370, 1560s, 1350, 1280, 1130
1 H NMR (CDCl 3 ) δ (ppm) 500 MHz: 8.33(d, J=2 Hz, 1H, Py-H), 7.91(dd, J 1 =2 Hz, J 2 =8 Hz, 1H, Py-H), 7.32(t, J=8 Hz, 1H, Py-H), 4.75(d, J 1 =15 Hz, J 2 =15 Hz, 2H, —CH 2 —N—), 4.66(t, J 1 =3 Hz, J 2 =3 Hz, 1H, —CHO—), 3.85(m, 4H, —O—(CH 2 ) 2 —), 3.57(m, 4H, imidazolidine-H), 2.88 (m, 2H, —CH 2 CH 2 —), 1.93(m, 2H, —CH 2 CH 2 —)
Elementary analysis Calculated: C 48.27, H 4.86, N 15.01; found C 48.47, H 4.95, N 14.40
EXAMPLE 8
Synthesis of 1-((6-chloropyridin-3-yl)methyl)-9-nitro-2,3,4,6,7,8-hexahydro-1H-pyrido[1,2-a]pyrimidin-6-ol (compound 8)
(1): Synthesis of N 1 -((6-chloropyridin-3-yl)methyl)propane-1,3-diamine









To a stirred solution of 2.07 g (0.015 mol) of potassium carbonate and 6.25 ml (0.075 mol) of propane-1,3-diamine in a 50 ml of flask placed in an ice bath, 2.42 g (0.015 mol) of 2-chloro-5-(chloromethyl)pyridine dissolved in 15 ml of acetonitrile was added dropwise and slowly for nearly 20 min. After addition, the ice bath was removed and then the mixture was stirred at room temperature for 8 hours. After the reaction was stopped, a large amount of water was added to dissolve potassium carbonate and propane-1,3-diamine, and the mixture was extracted with dichlormethane. The lower organic phase was collected, dried, and evaporated to dryness (It was better to remove all of the propane-1,3-diamine in the solvent since its presence would influence the following step). The obtained product was yellow oily liquid in 68% yield.
GC MS(m/s) 199 (5) M + , 182(10), 167(12), 155(17), 141(24), 126(100), 99(10), 90(13), 73(25), 56(10).
(2): Synthesis of 1-((6-chloropyridin-3-yl)methyl)-2-(nitromethylene)hexahydro pyrimidine









2.5 g (0.0178 mol) of 1,1-dimethylthio-2-nitroethene, 3.6 g (0.0178 mol) of N 1 -((6-chloropyridin-3-yl)methyl)propane-1,3-diamine were added to 15 ml of ethanol. The resulting mixture was heated under reflux for 4 hours at 80-90 ° C. The mixture was then cooled to educe solid, concentrated, filtrated and dried to give light yellow powder in 56% yield.
R f =0.19 (ethanol: dichlormethane =1:1)
Mp=175.7° C.-182.6° C.
GC MS (m/s) 225(100), 196(9), 154(10), 139(11), 126(31), 113(10), 99(31)
(3): Synthesis of 1-((6-chloropyridin-3-yl)methyl)-9-nitro-2,3,4,6,7,8-hexahydro -1H-pyrido[1,2-a]pyrimidin-6-ol









The preparation method was the same as that of example 1, except using 1-((6-chloropyridin-3-yl)methyl)-2-(nitromethylene)hexahydropyrimidine as a starting material. The reaction was stopped and the precipitated solid was filtrated to give a crude product, which was recrystallized to give the pure product in 51 % yield.
Mp=172.7-173.9° C.
IR (KBr, cm −1 ) 2900, 2370, 1680, 1560, 1400, 1340, 1140, 980, 750, 590
1 HNMR (CDCl 3 ) δ (ppm) 500 MHz: 8.28(d, J=2 Hz, 1H, Py-H), 7.74(dd,J=2 Hz, J 2 =2Hz 1H, Py-H), 7.48(d, J=8Hz, 1H, Py-H), 6.37(s, 1H, —OH), 4.82(s, 1H, —CHOC), 4.46(d,J 1 =15 Hz, J 2 =15 Hz, 2H, —CH 2 —N—), 2.93(m, 4H, pyrimidine-H), 1.83(m, 2H, pyrimidine-H, 2H, —CH 2 CH 2 —), 1.07(m, 2H, —CH 2 CH 2 —). GC MS (m/s) 225(100), 196(9) 154(10), 139(11), 126(31), 113(10), 99(31)
Elementary analysis Calculated: C51.78, H 5.28, N 17.25; found C 52.92, H 5.36, N 17.11
EXAMPLE 9
Synthesis of 1-((2-chlorothiazol-5-yl)methyl)-8-nitro- 1,2,3,5,6,7-hexahydro imidazo[1,2-a]pyridin-5-ol (compound 9)
(1): Synthesis of N 1 -((2-chlorothiazol-5-yl)methyl)ethane-1,2-diamine









To a stirred solution of 0.03 mol of potassium carbonate and 10 ml (0.15 mol) of ethylenediamine in a 50 ml of flask placed in an ice bath, 0.03 mol of 2-chloro-5-(chloromethyl)thiazole dissolved in 15 ml of acetonitrile was added dropwise and slowly. After addition, the ice bath was removed and then the mixture was stirred for 8 hours at room temperature. After the reaction was stopped, a large amount of water was added to dissolve potassium carbonate and ethylenediamine, and the mixture was extracted with dichlormethane. The lower organic phase was collected, dried, and evaporated to dryness. The obtained product was yellow oily liquid in 70% yield.
GC MS (m/s) 191 (21) M + , 132(100).
(2): Synthesis of 1-((2-chlorothiazol-5-yl)methyl)-2-(nitromethylene)- 1-imidazolidine









2.5 g (0.0178 mol) of 1,1-dimethylthio-2-nitroethene, 3.3 g (0.0178 mol) of N 1 -((2-chlorothiazol-5-yl)methyl)ethane-1,2-diamine were added to 15 ml of ethanol. The resulting mixture was heated under reflux for 4 hours at 80-90° C. The mixture was then cooled to educe solid, concentrated, filtrated and dried to give a light yellow powder in 56% yield.
GC MS(m/s) 226 (24), 132(100), 77(9).
(3): Synthesis of 1 -((2-chlorothiazol-5-yl)methyl)-8-nitro- 1,2,3,5,6,7-hexahydroimidazo [1,2-a]pyridin-5-ol









A mixture of 0.002 mol of 1-((2-chlorothiazol-5-yl)methyl)-2-(nitromethylene) imidazolidine, 15 ml of anhydrous acetonitrile, 0.15 ml of acrylaldehyde and a catalytic amount of HCl place in a 50 ml of flask was heated to 40° C. and the mixture was kept at 40° C. and stirred for 12 hours. The precipitated solid was filtrated to give a crude product. After recrystallization, the pure product was a yellow powder in 40% yield.
Mp=172-174.6° C.
IR (KBr, cm −1 ) 3194, 1564, 1545, 1373, 1310, 1150
Elementary analysis Calculated: C47.71, H 4.14, N 17.69; found C 47.89, H 4.35, N 17.45
EXAMPLE 10
Synthesis of 1-((2-chlorothiazolyl-5-yl)methyl)-5-ethoxy-8-nitro-1,2,3,5,6,7-hexahydroimidazo[1,2-a]pyridine (compound 10)









0.001 mol of compound 9 was added to a 50 ml of round-bottomed flask, and then 15 ml of methanol and a catalytic amount of glacial acetic acid were added. The resulting mixture was refluxed and followed by TLC. After the reaction was stopped, the solvent was removed. The residue was then separated to give a pure yellow powder by column chromatography in 85% yield.
Mp=128.4-129.2° C.
IR (KBr) 3052 m, 2872 m, 1573 vs, 1503s, 1312 vs, 1150vs, 1030s cm −1 ,
Elementary analysis Calculated: C 45.28, H 4.97, N 16.25; found C 45.19, H 4.92, N 16.56
EXAMPLE 11
Synthesis of 8-nitro-1-((tetrahydrofuran-3-yl)methyl)-1,2,3,5,6,7-hexahydro imidazo[1,2-a]pyridin-5-ol (compound 11)
(1): Synthesis of N 1 -((tetrahydrofuran-3-yl)methyl)ethane-1,2-diamine









A mixture of 0.2 mol of 3-(chloromethyl)tetrahydrofuran, 200 ml of ethanol, 0.2 mol of potassium carbonate and 0.2 mol of ethylenediamine placed in a 500 ml of round-bottomed flask was refluxed for 24 hours, and then the solvent was removed. The obtained product was yellow oily liquid in 77% yield.
GC MS (m/s) 144 (67), 99(100)
(2): Synthesis of 2-(nitromethylene)-1-((tetrahydrofuran-3-yl)methyl) imidazolidine









2.5 g (0.0178 mol) of 1,1-dimethylthio-2-nitroethene, 2.56 g (0.0178 mol) of N 1 -((tetrahydrofuran-3-yl)methyl)ethane-1,2-diamine were added to 50 ml of ethanol. The resulting mixture was heated under reflux for 8 hours at 80-90 ° C. The mixture was then cooled to educe solid, concentrated, filtrated and dried to give a light yellow powder in 81% yield.
GC MS (m/s) 177(29), 99(100), 56(9).
(3): Synthesis of 8-nitro-1-((tetrahydrofuran-3-yl)methyl)-1,2,3,5,6,7-hexahydro imidazo[ 1,2-a]pyridin-5-ol









A mixture of 0.002 mol of 2-(nitromethylene)-1-((tetrahydrofuran-3-yl)methyl)imidazolidine, 15 ml of anhydrous acetonitrile, 0.15 ml of acrylaldehyde and a catalytic amount of HCl place in a 50 ml of flask was heated to 40° C. and the mixture was kept at 40° C. and stirred for 12 hours. The reaction was stopped and the solvent was removed to obtain a crude solid. After recrystallization, the pure product, which was a light yellow powder, was obtained in 67% yield.
Mp=144.2-146.1 ° C.
IR (KBr, cm −1 ) 3194, 1564, 1545, 1373, 1300, 1310, 1293, 1150.
Elementary analysis Calculated: C53.52, H 7.11, N 15.60; found C 53.78, H 7.12, N 15.35
EXAMPLE 12
Synthesis of 8-nitro-5-propoxy-1-((tetrahydrofuran-3-yl)methyl)-1,2,3,5,6,7-hexahydroimidazo[1,2-a]pyridine (compound 12)









0.001 mol of compound 11 was added to a 50 ml of round-bottomed flask, and 15 ml of propanol and a catalytic amount of glacial acetic acid were added. The resulting mixture was refluxed and followed by TLC. After the reaction was stopped, the solvent was removed. The residue was then separated to give a pure yellow powder by column chromatography in 85% yield.
Mp=96.4-97.2° C.
IR (KBr) 3052 m, 2872 m, 1573 vs, 1503s, 1312 vs, 1300 m, 1297 vs, 1150 vs, 1030s cm −1
Elementary analysis Calculated: C 57.86, H 8.09, N 13.49; found C 58.04, H 7.97, N 13.42
EXAMPLE 13
Synthesis of 1-((6-chloropyridin-3-yl)methyl)-8-nitro-1,2,3,5,6,7-hexahydro imidazo[1,2-a]pyridin-5-yl acetate (compound 13)









0.001 mol of compound 1 was added to a 50 ml of round-bottomed flask, and, 0.001 mol of acetic anhydride and 0.001 mol of pyridine were added. The resulting mixture was stirred at room temperature and followed by TLC. After the reaction was stopped, the solvent was removed. Then the residue was separated to give a pure light yellow powder by column chromatography in 70% yield.
Mp=134-134.7° C.
IR (KBr cm −1 ) 2903, 2370, 1713, 1332, 1203, 1123, 1071, 1000, 973, 830, 592
1 HNMR (CDCl 3 ) δ (ppm) 500 MHz: 8.33(d, J=2 Hz, 1H, Py-H), 7.88(dd, J 1 =2 Hz, J 2 =8 Hz, 1H, Py-H), 7.36(d, J=8 Hz, 1H, Py-H), 4.79(d, J 1 =15 Hz, J 2 =15 Hz, 2H, —CH 2 —N—), 4.48(t, J 1 =3 Hz,J 2 =3 Hz, 1H, —CHO—), 4.12(m, 3H, —OCOCH 3 ), 3.62(m, 4H, imidazolidine-H), 2.97(m, 2H, —CH 2 CH 2 —), 2.12(m, 2H, —CH 2 CH 2 —).
Elementary analysis Calculated: C 51.07, H 4.86, N 15.88; found C 51.23 H 4.88, N 15.92
EXAMPLE 14
Synthesis of 1-((6-chloropyridin-3-yl)methyl)-5-(ethylthio)-8-nitro-1,2,3,5,6,7-hexahydroimidazo[1,2-a]pyridine (compound 14)









0.31 g (0.001 mol) of compound 1 was added to a 50 ml of round-bottomed flask, and 15 ml of ethanethiol and a catalytic amount of Boron trifluoride dissolved in tetrahydrofuran were added. The resulting mixture was refluxed and followed by TLC. After the reaction was stopped, the solvents were removed. The residue was then separated to give a pure yellow powder by column chromatography in 90% yield.
Mp=167.2-168.3° C.; IR (KBr, cm −1 ) 2902, 1563, 1350, 1078, 900, 760, 590
1 HNMR (CDCl 3 ) δ (ppm) 500 MHz: 8.31(d, J=2 Hz, 1H, Py-H), 7.89(dd, J 1 =2 Hz, J 2 =8Hz, 1H, Py-H), 7.35(d, J=8 Hz, 1H, Py-H), 4.71(d, J 1 =15 Hz, J 2 =15 Hz, 2H, —CH 2 —N—), 4.32(t, J 1 =3 Hz,J 2 =3 Hz, 1H, —CHO—), 3.60(m, 4H, imidazolidine-H), 2.89(m, 3H, —SCH 3 ), 2.90(m, 2H, —CH 2 CH 2 —), 1.91(m, 2H, —CH 2 CH 2 —)
Elementary analysis Calculated: C 49.34,H 5.03,N 16.44; found C 48.98,H 5.23,N 16.48
EXAMPLE 15
Synthesis of (E)-1-((6-chloropyridin-3-yl)methyl)-8-nitro-2,3,6,7-tetrahydro imidazo[1,2-a]pyridin-5(1H)-one oxime
(1): Synthesis of 1-((6-chloropyridin-3-yl)methyl)-8-nitro-2,3,6,7-tetrahydro imidazo[1,2-a]pyridin-5(1H)-one









A mixture of 0.509 g (0.002 mol) of 2-chloro-5-((2-(nitromethylene)imidazolidin-1-yl) methyl)pyridine, 15 ml of anhydrous methanol and 0.002 mol methyl acrylate placed in a 50 ml of flask was refluxed for 30 hours and then separated to give a product by column chromatography in 40% yield.
Mp=167.0-168.1° C.
IR (KBr, cm −1 ) 3190, 1685, 1612
MS: m/z=308.
(2): Synthesis of (E)-1-((6-chloropyridin-3-yl)methyl)-8-nitro-2,3,6,7-tetrahydro imidazo[1,2-a]pyridin-5(1H)-one oxime









A mixture of 0.618 g (0.002 mol) of 1-((6-chloropyridin-3-yl)methyl)-8-nitro-2,3,6,7-tetrahydroimidazo[1,2-a]pyridin-5(1H)-one, 0.01 mol of hydroxylamine hydrochloride, 0.01 mol of potassium hydroxide and 20 ml of ethanol placed in a 100 ml of flask was refluxed for 24 hours. The solvent was removed and the residue was separated to give a product by column chromatography in 65% yield.
Mp=189.1-190.3° C.
1 HNMR (CDCl 3 ) δ (ppm) 500 MHz: 8.34(d, J=2Hz, 1H, Py-H), 7.89(dd, J 1 =2 Hz, J 2 =8 Hz, 1H, Py-H), 7.41(d, J=8 Hz, 1H, Py-H), 4.79(d, J 1 =15 Hz, J 2 =15 Hz, 2H, —CH 2 —N—), 3.62(m, 4H, imidazolidine-H), 3.97(m, 2H, —CH 2 CH 2 —), 2.96(m, 2H, —CH 2 CH 2 —)
Elementary analysis Calculated: C 48.23,H 4.36,N 21.63; found C 48.02,H 4.42,N 21.92
EXAMPLE 16
Synthesis of (E)-1-((6-chloropyridin-3-yl)methyl)-8-nitro-2,3,6,7-tetrahydro imidazo [1,2-a]pyridin-5(1H)-one 0-methyl oxime (compound 16)









The mixture of 0.002 mol of compound 15, 0.002 mol of sodium methoxide, 0.002 mol of methyl iodide and 20 ml of methanol placed in a 100 ml of flask was stirred at room temperature for 20 hours, evaporated to remove solvent and then separated to give a pure product by column chromatography in 56% yield. Mp=156.2-156.7° C.
1 HNMR (CDCl 3 ) δ (ppm)500 MHz: 8.35(d, J=2 Hz, 1H, Py-H), 7.90(dd, J 1 =2 Hz, J 2 =8 Hz, 1H, Py-H), 7.39(d, J=8 Hz, 1H, Py-H), 4.78(d, J 1 =15 Hz, J 2 =15 Hz, 2H, —CH 2 —N—), 3.62(m, 4H, imidazolidine-H), 3.99(m, 2H, —CH 2 CH 2 —), 3.69(s, 1H, —OCH 3 ), 2.93(m, 2H, —CH 2 CH 2 —). Elementary analysis Calculated: C 49.78,H 4.77,N 20.73; found C 40.89,H 4.69,N 21.21
EXAMPLE 17-227
According to a similar method described in example 1-16,the compound Nos. 17-227 in table 1 were obtained using proper starting materials.
The compound of the present invention can be used to control and kill general insects, including sucking insects, biting insects and other plant parasite, storage cereal insects and health hazard insects.
The examples of insects are listed as follow:
Coleoptera: Sitophilus zeamais, Tribolium castaneum, Henosepilachna vigintioctomaculata, Agriotes fuscicollis, Monolepta hieroglyphica, Diabrotica SPP, Anomala cupripes, Monochamus alternatus, Echinocnemus squameus, Lyrtus hrunneus
Lepidoptera: Lymantria dispar, Malacosoma neustria testacea, Prodenia litura, Mamestra brassicae, Chilo stuppressalis, Ostrinia nubilalis, Cadra cautella, Adoxophyes orana, Laspeyresia splendana, Agrotis fucosa, Galleria mellonella, Plutella xylostella, Phyllocnistis citrella
Hemiptera: Nephotettix cincticeps, Nilaparvata lugens, Pseudococcus comstocki, Unaspis yanonensis, Myzus persicae, Aphis pomi, Lipaphis erysimi pseudobrassicae, Stephanitis nashi, Nazara SPP, Cimicidae, Trialeurodes vaporariorum , and Psylle SPP.
Orthoptera: Blattella germanica, Periplaneta americana, Gryllotalpa africana, Locusta migratoria .
Isoptera: Deucotermes speratits, Coptotermes formosanus
Diptera: Musca domestica, Aedes aegypti, Hylemya platura, Delia platura, Anopheles sinensi.
The compounds in this invention have special effects to insects having a piercing-sucking or scratching mouthparts, such as aphid, leafhopper, planthopper, thrips, white fly.
These active compounds can be prepared into the customary formulations, such as solutions, emulsions, suspensions, powders, foams, pastes, granules, aerosols, natural and synthetic materials impregnated with active compounds, and micro-capsules in polymers used in the coating complex for seed, preparations used with a combustion device (such as smoking cylindrantherae, smoking can and smoking plate) and ULV cold mist and warm mist preparations. These formulations may be produced in a known manner, for example, by mixing the active compounds with extenders, which are liquid or liquefied gaseous or solid diluents or carriers, optionally with the use of surface-active agents, that is to say emulsifying agents and/or dispersing agents, and/or foam-forming agents. In the case of using water as an extender, organic solvents can, for example, also be used as auxiliary solvents
It is generally proper to use liquid solvents as a diluent or carrier, for example, aromatic hydrocarbons, such as xylene, toluene and alkyl naphthalenes, chlorinated aromatic or chlorinated aliphatic hydrocarbons, such as chlorobenzenes, chloroethylenes and methylene chloride, aliphatic hydrocarbons, such as cyclohexane or paraffins, for example, mineral oil fractions, alcohols, such as butanol or glycol as well as their ethers and esters, ketones, such as acetone, methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone, or uncommon polar solvents, such as dimethylformamide and dimethylsulfoxide, as well as water.
By liquefied gaseous diluents or carriers are meant liquids which are gaseous at normal temperature and under normal pressure, for example, aerosol propellants, such as halogenated hydrocarbons as well as butane, propane, nitrogen and carbon dioxide.
The solid carrier can use ground natural minerals, such as kaolins, clays, talcs, quartzs, attapulgites, montmorillonites or kieselguhrs; ground synthetic minerals, such as high-dispersed silicic acid, alumina and silicate. The solid carrier used for particles is crushed and fractionated natural rocks such as calcite, marble, pumice, sepiolite and dolomite, as well as synthetic granules of inorganic and organic coarse powder, and granules of organic material such as sawdust, coconut shells, maize cobs and tobacco stalks and the like.
Nonionic and anionic emulsifiers may be used as emulsifying and/or foam-forming agents, such as polyoxyethylene-fatty acid esters, polyoxyethylene-fatty alcohol ethers, for example, alkylaryl polyglycol ethers, alkylsulfonates, alkylsulfates, arylsulfonates as well as albumin hydrolysis products. Dispersing agents include, for example, lignin sulfite waste liquors and methylcellulose.
Adhesives such as carboxymethyl cellulose and natural and synthetic polymers, (such as gum arabic, polyvinyl alcohol and polyvinyl acetate) in the form of powders, granules or emulsions can be used in the formulations
It is possible to use colorants such as inorganic dyestuffs, for example, iron oxide, cobalt oxide and Prussian Blue, and organic dyestuffs, such as diazo dyestuffs or metal phthalo-cyanine dyestuffs, and trace nutritional agent, such as the salts of iron, manganese, boron, copper, cobalt, aluminum and zinc.
The formulations, in general, contain from 0.01 to 99.99 percent by weight of active compound, preferably 0.1-99.wt %, more preferably 0.5-90.wt %.
The active compound of the present invention can be present as a mixture with other active compounds in a commercial formulation or a use form prepared from the commercial formulation. The other compound can be insecticide, bactericide, acaricide, nematocide, fungicide, growth controller and the like. The insecticide includes phosphates, carbamate, pyrethroids, chlorinated hydrocarbons, benzoylurea, nereistoxin and material produced by microbion such as avermectin.
Furthermore, the active compound of the present invention can be present as a mixture with a synergist in a commercial formulation or a use form prepared from the commercial formulation. Synergist is used to enhance the action of active compound, so if the compound itself is active there is no need to use it.
The concentration of the active compound in the use form prepared from the commercial formulation can vary within a wide range. The active compound concentration of the formulation for use is, for example, from 0.0000001 to 100 percent by weight of active compound, preferably from 0.0001 to 1 percent by weight.
These compounds can be prepared into proper dosage forms and used by common methods
Activity Test
Test on the insecticidal activity of Compound Nos. 1-227
Aphis, which belongs to Homoptera and has a piercing-sucking mouthpart, is a common insect for agricultural plant. Aphis craccivoral was tested by the way of immersing.
Test method: exactly weighed various samples were independently added to N,N-dimethylformamide to form a 10 g/L stock solution. The mixture was diluted with 0.2 mL/L aqueous Triton X-100 solution to a concentration of 500 ug/mL. After stably sucking on bean sprout, the adult aphis without wings together with bean sprout was dipped into 500 ug/mL dilution, taken out after 5 seconds, and the excess dilution was sucked out with bibulous paper and the adult aphis without wings was incubated in clean vessel at a constant temperature of 23° C. Each concentration was repeated for 3 times and the control group contained 0.2 mL/L aqueous Triton X-100 solution. The number of killed aphis was counted after 24 hours to calculate the mortality. The result was shown in Table 1 bellow
Planthopper, which belongs to Homoptera and has a piercing-sucking mouthpart, is a common insect for agricultural plant. Nilaparvata lugens was tested by the way of spraying.
Test method: the test compound was exactly formulated into a solution having a certain concentration and clean water was used as a blank control. Each process was repeated for 3 tumblers (3 times). 2 ml of solution was sprayed uniformly to each tumbler by a mini manual sprayer. 10 Nilaparvata lugens were introduced to every sink 6 hours before spraying. Three series of experiments were conducted. The number of killed Nilaparvata lugens was counted after 24 hours to calculate the mortality. The result was shown in Table 1 bellow.
TABLE 1 mortality (%) (500 ppm) Nilapar- Compound Melting point vata- number R 1 R 2 R 3 R 4 A n (° C.) Aphis lugens 1 H H H —O 0 169-172 96 100 2 CH 3 H H —O 0 154-155 100 100 3 CH 2 CH 3 H H —O 0 126-128 100 100 4 CH 2 CH 2 Cl H H —O 0 158-159 76 100 5 CH 2 CF 3 H H —O 0 112-113 100 100 6 CH 2 CH 2 CH 3 H H —O 0 115-117 100 100 7 CH(CH 3 ) 2 H H —O 0 130-134 100 100 8 CH 2 (CF 3 ) 2 H H —O 0 98-99 80 100 9 CH 2 (CH 2 ) 2 CH 3 H H —O 0 104-106 76 97 10 CH 2 CH(CH 3 ) 2 H H —O 0 115-116 100 100 11 CH(CH 3 )CH 2 CH 3 H H —O 0 116-117 36 86 12 C(CH 3 ) 3 H H —O 0 145-147 100 100 13 C(CH 3 ) 2 CCl 3 H H —O 0 192-193 56 90 14 CH 2 (CH 2 ) 3 CH 3 H H —O 0 83-85 52 100 15 CH 2 CH 2 CH(CH 3 ) 2 H H —O 0 110-111 67 97 16 CH(CH 3 )(CH 2 ) 2 CH 3 H H —O 0 125-126 89 100 17 CH 2 C(CH 3 ) 3 H H —O 0 168-170 100 100 18 H H —O 0 136-137 23 67 19 CH 2 CH═CH 2 H H —O 0 146-147 35 78 20 CH 2 C═CH H H —O 0 168-169 39 56 21 CH 2 CH 2 OCH 3 H H —O 0 117-118 100 100 22 CH 2 CH 2 OCH 2 CH 3 H H —O 0 108-109 100 100 23 H H H —O 0 172-174 87 100 24 CH 3 H H —O 0 150-151 100 100 25 CH 2 CH 3 H H —O 0 128-129 100 100 26 CH 2 CH 2 Cl H H —O 0 161-162 26 64 27 CH 2 CF 3 H H —O 0 115-116 100 100 28 CH 2 CH 2 CH 3 H H —O 0 117-119 100 100 29 CH(CH 3 ) 2 H H —O 0 133-135 100 100 30 CH 2 (CF 3 ) 2 H H —O 0 98-99 58 98 31 CH 2 (CH 2 ) 2 CH 3 H H —O 0 104-106 56 35 32 CH 2 CH(CH 3 ) 2 H H —O 0 115-116 37 23 33 CH(CH 3 )CH 2 CH 3 H H —O 0 116-117 24 56 34 C(CH 3 ) 3 H H —O 0 145-147 100 100 35 C(CH 3 ) 2 CCl 3 H H —O 0 189-190 98 100 36 CH 2 (CH 2 ) 3 CH 3 H H —O 0 87-89 34 57 37 CH 2 CH 2 CH(CH 3 ) 2 H H —O 0 111-112 56 64 38 CH(CH 3 )(CH 2 ) 2 CH 3 H H —O 0 127-129 35 67 39 CH 2 C(CH 3 ) 3 H H —O 0 169-170 24 35 40 H H —O 0 141-142 45 67 41 CH 2 CH═CH 2 H H —O 0 152-154 89 100 42 CH 2 C≡CH H H —O 0 171-172 45 100 43 CH 2 CH 2 OCH 3 H H —O 0 117-119 100 100 44 CH 2 CH 2 OCH 2 CH 3 H H —O 0 112-114 67 100 45 H H H —O 0 144-146 56 89 46 CH 3 H H —O 0 130-131 100 100 47 CH 2 CH 3 H H —O 0 101-102 45 100 48 CH 2 CH 2 Cl H H —O 0 127-129 3 0 49 CH 2 CF 3 H H —O 0 97-98 45 32 50 CH 2 CH 2 CH 3 H H —O 0 96-97 100 100 51 CH(CH 3 ) 2 H H —O 0 108-109 34 23 52 CH 2 (CF 3 ) 2 H H —O 0 82-83 34 12 53 CH 2 (CH 2 ) 2 CH 3 H H —O 0 96-98 9 12 54 CH 2 CH(CH 3 ) 2 H H —O 0 101-102 23 34 55 CH(CH 3 )CH 2 CH 3 H H —O 0 111-112 45 12 56 C(CH 3 ) 3 H H —O 0 123-125 100 100 57 C(CH 3 ) 2 CCl 3 H H —O 0 181-184 34 38 58 CH 2 (CH 2 ) 3 CH 3 H H —O 0 68-70 34 23 59 CH(CH 3 )CH 2 CH 3 H H —O 0 98-99 2 3 60 CH 2 CH 2 CH(CH 3 ) 2 H H —O 0 113-115 3 5 61 CH(CH 3 )(CH 2 ) 2 CH 3 H H —O 0 121-122 56 89 62 CH 2 C(CH 3 ) 3 H H —O 0 136-137 12 23 63 H H —O 0 121-125 2 6 64 CH 2 CH═CH 2 H H —O 0 135-137 37 46 65 CH 2 C≡CH H H —O 0 156-157 47 34 66 CH 2 CH 2 OCH 3 H H —O 0 117-118 100 100 67 CH 2 CH 2 OCH 2 CH 3 H H —O 0 98-99 100 100 68 H Me H —O 0 146-147 2 7 69 H Me H —O 0 164-165 45 56 70 H Me H —O 0 165-166 33 12 71 H H H —O 1 172-173 6 0 72 CH 3 H H —O 1 156-157 35 100 73 CH 2 CH 3 H H —O 1 129-130 34 56 74 CH 2 CH 2 Cl H H —O 1 160-161 12 13 75 CH 2 CF 3 H H —O 1 114-115 88 100 76 CH 2 CH 2 CH 3 H H —O 1 118-119 100 100 77 CH(CH 3 ) 2 H H —O 1 135-137 56 78 78 CH 2 (CF 3 ) 2 H H —O 1 102-103 68 51 79 CH 2 (CH 2 ) 2 CH 3 H H —O 1 114-115 52 61 80 CH 2 CH(CH 3 ) 2 H H —O 1 124-126 23 34 81 CH(CH 3 )CH 2 CH 3 H H —O 1 127-128 12 8 82 C(CH 3 ) 3 H H —O 1 195-197 12 34 83 CH 2 CH 2 OCH 3 H H —O 1 167-168 38 26 84 CH 2 CH 2 OCH 2 CH 3 H H —O 1 169-170 26 39 85 H H H —O 1 175-176 12 23 86 CH 3 H H —O 1 158-159 100 100 87 CH 2 CH 3 H H —O 1 128-130 100 100 88 CH 2 CH 2 Cl H H —O 1 165-168 23 34 89 CH 2 CF 3 H H —O 1 119-120 100 100 90 CH 2 CH 2 CH 3 H H —O 1 123-125 34 51 91 CH(CH 3 ) 2 H H —O 1 138-139 69 71 92 CH 2 (CF 3 ) 2 H H —O 1 112-116 6 5 93 CH 2 (CH 2 ) 2 CH 3 H H —O 1 118-119 7 8 94 CH 2 CH(CH 3 ) 2 H H —O 1 128-129 8 3 95 CH(CH 3 )CH 2 CH 3 H H —O 1 131-133 4 8 96 C(CH 3 ) 3 H H —O 1 199-200 80 100 97 CH 2 CH 2 OCH 3 H H —O 1 169-170 78 100 98 CH 2 CH 2 OCH 2 CH 3 H H —O 1 165-167 4 7 99 H H H —O 1 162-163 6 7 100 CH 3 H H —O 1 143-145 3 8 101 CH 2 CH 3 H H —O 1 113-112 76 90 102 CH 2 CH 2 Cl H H —O 1 146-148 0 89 103 CH 2 CF 3 H H —O 1 102-103 6 100 104 CH 2 CH 2 CH 3 H H —O 1 108-109 3 24 105 CH(CH 3 ) 2 H H —O 1 117-119 10 98 106 CH 2 (CF 3 ) 2 H H —O 1 98-99 45 100 107 CH 2 (CH 2 ) 2 CH 3 H H —O 1 104-106 7 0 108 CH 2 CH(CH 3 ) 2 H H —O 1 109-111 1 9 109 CH(CH 3 )CH 2 CH 3 H H —O 1 113-115 2 10 110 C(CH 3 ) 3 H H —O 1 178-179 67 98 111 H H —O 0 187-189 1 23 112 H H —O 0 193-195 38 75 113 COCH 3 H H —O 0 167-169 45 77 114 COCH 2 CH 3 H H —O 0 165-166 56 88 115 COCCl 3 H H —O 0 194-196 0 33 116 COCF 3 H H —O 0 135-137 2 45 117 SO 2 CH 3 H H —O 0 178-179 19 65 118 SO 2 CF 3 H H —O 0 167-168 81 100 119 H H —O 0 196-197 3 23 120 H H —O 0 182-184 1 5 121 H H —O 0 183-185 0 8 122 H H —O 0 176-178 56 23 123 H H —O 0 176-177 56 100 124 H H —O 0 183-186 22 0 125 H H —O 0 156-158 67 92 126 H H —O 0 178-179 93 100 127 H H —O 0 180-181 45 78 128 H H —O 0 193-195 0 21 129 H H —O 0 196-197 0 34 130 H H —O 0 201-202 23 67 131 H H —O 0 197-199 3 0 132 CH 3 H H —S 0 167-168 100 100 133 CH 2 CH 3 H H —S 0 145-147 100 100 134 CH 2 CH 2 Cl H H —S 0 178-179 34 78 135 CH 2 CF 3 H H —S 0 156-158 98 100 136 CH 2 CH 2 CH 3 H H —S 0 136-138 100 100 137 CH(CH 3 ) 2 H H —S 0 151-152 89 100 138 CH 2 (CF 3 ) 2 H H —S 0 137-138 45 98 139 CH 2 (CH 2 ) 2 CH 3 H H —S 0 124-125 34 78 140 CH 2 CH(CH 3 ) 2 H H —S 0 135-138 67 78 141 CH(CH 3 )CH 2 CH 3 H H —S 0 139-140 56 89 142 C(CH 3 ) 3 H H —S 0 160-161 67 88 143 CH 2 (CH 2 ) 3 CH 3 H H —S 0 112-113 23 34 144 CH(CH 3 )CH 2 CH 3 H H —S 0 128-129 12 56 145 CH 2 CH 2 CH(CH 3 ) 2 H H —S 0 131-132 67 78 146 CH(CH 3 )(CH 2 ) 2 CH 3 H H —S 0 129-130 35 97 147 CH 2 C(CH 3 ) 3 H H —S 0 138-139 56 99 148 CH 2 CH 2 OCH 3 H H —S 0 128-129 67 89 149 CH 2 CH 2 OCH 2 CH 3 H H —S 0 126-127 98 100 150 H H —O 0 186-187 3 67 151 H H —O 0 197-199 2 16 152 COCH 3 H H —O 0 169-170 3 0 153 COCH 2 CH 3 H H —O 0 168-169 29 38 154 COCCl 3 H H —O 0 197-198 93 100 155 COCF 3 H H —O 0 138-139 48 90 156 SO 2 CH 3 H H —O 0 178-180 78 92 157 SO 2 CF 3 H H —O 0 169-171 56 100 158 H H —O 0 198-199 6 7 159 H H —O 0 186-187 0 8 160 H H —O 0 187-189 4 8 161 H H —O 0 177-178 3 5 162 H H —O 0 179-180 34 98 163 H H —O 0 187-188 1 0 164 H H —O 0 163-165 59 78 165 H H —O 0 184-188 90 100 166 H H —O 0 185-188 0 45 167 H H —O 0 193-194 12 4 168 H H —O 0 198-199 56 100 169 H H —O 0 207-209 2 13 170 H H —O 0 195-196 2 0 171 CH 3 H H —S 0 169-170 97 100 172 CH 2 CH 3 H H —S 0 148-149 100 100 173 CH 2 CH 2 Cl H H —S 0 179-181 45 56 174 CH 2 CF 3 H H —S 0 159-161 67 100 175 CH 2 CH 2 CH 3 H H —S 0 139-140 89 100 176 CH(CH 3 ) 2 H H —S 0 155-156 78 98 177 CH 2 (CF 3 ) 2 H H —S 0 141-142 56 65 178 CH 2 (CH 2 ) 2 CH 3 H H —S 0 127-128 23 12 179 CH 2 CH(CH 3 ) 2 H H —S 0 138-139 12 56 180 CH(CH 3 )CH 2 CH 3 H H —S 0 142-143 34 78 181 C(CH 3 ) 3 H H —S 0 166-167 45 78 182 CH 2 (CH 2 ) 3 CH 3 H H —S 0 117-119 67 87 183 CH 2 CH 2 CH(CH 3 ) 2 H H —S 0 136-137 23 34 184 CH(CH 3 )(CH 2 ) 2 CH 3 H H —S 0 131-132 12 35 185 CH 2 C(CH 3 ) 3 H H —S 0 143-144 36 86 186 CH 2 CH 2 OCH 3 H H —S 0 132-133 97 100 187 CH 2 CH 2 OCH 2 CH 3 ) 3 H H —S 0 127-129 34 97 188 H H H ═N 0 189-190 55 67 189 CH 3 H H ═N 0 156-157 100 100 190 CH 2 CH 3 H H ═N 0 146-147 89 100 191 CH 2 CH 2 Cl H H ═N 0 176-177 53 78 192 CH 2 CH 2 CH 3 H H ═N 0 125-127 86 100 193 CH(CH 3 ) 2 H H ═N 0 137-137 93 98 194 CH 2 CH 2 CH 2 CH 3 H H ═N 0 118-119 34 45 195 CH 2 (CH 2 ) 3 CH 3 H H ═N 0 101-102 46 78 196 CH 2 CH 2 CH(CH 3 ) 2 H H ═N 0 123-124 12 25 197 CH(CH 3 )(CH 2 ) 2 CH 3 H H ═N 0 131-132 8 56 198 CH 2 C(CH 3 ) 3 H H ═N 0 143-144 39 89 199 CH 2 CH 2 OCH 3 H H ═N 0 121-123 16 36 200 CH 2 CH 2 OCH 2 CH 3 ) 3 H H ═N 0 119-120 45 78 201 H H H ═N 1 193-194 54 55 202 CH 3 H H ═N 1 163-165 89 98 203 CH 2 CH 3 H H ═N 1 151-155 92 100 204 CH 2 CH 2 Cl H H ═N 1 178-179 46 78 205 CH 2 CH 2 CH 3 H H ═N 1 128-129 35 100 206 CH(CH 3 ) 2 H H ═N 1 139-140 56 98 207 CH 2 CH 2 CH 2 CH 3 H H ═N 1 120-122 14 45 208 CH 2 (CH 2 ) 3 CH 3 H H ═N 1 104-106 35 67 209 CH 2 CH 2 CH(CH 3 ) 2 H H ═N 1 126-127 23 26 210 CH(CH 3 )(CH 2 ) 2 CH 3 H H ═N 1 135-136 7 77 211 CH 2 C(CH 3 ) 3 H H ═N 1 147-148 34 56 212 H H H ═N 0 203-205 34 23 213 CH 3 H H ═N 0 169-170 32 78 214 CH 2 CH 3 H H ═N 0 157-158 55 90 215 CH 2 CH 2 Cl H H ═N 0 182-183 9 97 216 CH 2 CH 2 CH 2 CH 3 H H ═N 0 136-138 66 98 217 CH 2 CH 2 CH 3 H H ═N 0 145-146 23 100 218 CH 2 (CH 2 ) 3 CH 3 H H ═N 0 129-130 45 67 219 CH(CH 3 ) 2 H H ═N 0 142-145 34 45 220 H H H ═N 1 205-207 16 56 221 CH 3 H H ═N 1 172-176 4 67 222 CH 2 CH 3 H H ═N 1 162-163 4 89 223 CH 2 CH 2 Cl H H ═N 1 185-186 5 76 224 CH 2 CH 2 CH 2 CH 3 H H ═N 1 137-138 45 66 225 CH 2 CH 2 CH 3 H H ═N 1 147-148 35 78 226 CH 2 (CH 2 ) 3 CH 3 H H ═N 1 133-135 22 57 227 CH(CH 3 ) 2 H H ═N 1 146-148 100 100

COMPOSITION EXAMPLE 1
(a) Oily Suspension
Any one of compounds 1-16 25 wt % Polyoxyethylene sorbital hexaoleate 5 wt % Higher aliphatic hydrocarbon oil 70 wt %

Each of the components was ground in a sand mill until the solid granules were reduced to less than about 5 micrometer. The resulting viscous suspension can be used directly or may be used after it was emulsified in water.
(b) Aqueous Suspension
Any one of compounds 1-16 25 wt % Hydrate attapulagit 3 wt % Calcium lignosulphonate 10 wt % Sodium dihydrogen phosphate 0.5 wt % Water 61.5 wt %

Each of the components was ground in a ball mill until the solid granules were reduced to less than about 10 micrometer. The aqueous suspension can be used directly.
All the documents cited herein are incorporated into the invention as reference, as if each of them is individually incorporated. Further, it would be appreciated that, in light of the above described teaching of the invention, the skilled in the art could make various changes or modifications to the invention, and these equivalents would still be within the scope of the invention defined by the appended claims of the application.