CN101381342B - Piperazine derivatives and applications thereof - Google Patents
Piperazine derivatives and applications thereof Download PDFInfo
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- CN101381342B CN101381342B CN2007100456616A CN200710045661A CN101381342B CN 101381342 B CN101381342 B CN 101381342B CN 2007100456616 A CN2007100456616 A CN 2007100456616A CN 200710045661 A CN200710045661 A CN 200710045661A CN 101381342 B CN101381342 B CN 101381342B
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- piperazine
- flumethiazine
- aromatic heterocyclic
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- KNJMXYXFQZPYLD-UHFFFAOYSA-N Clc1ccc(CN2CCNCC2)cn1 Chemical compound Clc1ccc(CN2CCNCC2)cn1 KNJMXYXFQZPYLD-UHFFFAOYSA-N 0.000 description 1
- QJZFGJZIYOPLOG-UHFFFAOYSA-N FC(c(cc1)cnc1N1CCN(Cc(cn2)ccc2Cl)CC1)(F)F Chemical compound FC(c(cc1)cnc1N1CCN(Cc(cn2)ccc2Cl)CC1)(F)F QJZFGJZIYOPLOG-UHFFFAOYSA-N 0.000 description 1
- JFZJMSDDOOAOIV-UHFFFAOYSA-N FC(c(cn1)ccc1Cl)(F)F Chemical compound FC(c(cn1)ccc1Cl)(F)F JFZJMSDDOOAOIV-UHFFFAOYSA-N 0.000 description 1
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Abstract
The invention relates to a piperazine derivate and application thereof. The piperazine derivate takes N<1>-arylmethyl and N<4>-pyridyl piperazine as parent matrixes to modify the structure of pesticides of main pharmacophore of the N1-arylmethyl and N4-pyridyl piperazine, so as to obtain a type of novel compound. As shown by biological (insect disinfestation) activity determination: the novel compound designed and synthesized by the invention can effectively inhibit feeding and growth of crolepidopteron, and cause the crolepidopteron to die. The piperazine derivate not only is helpful to the further research of 5-hydroxytryptamine receptors of insects but also provides direction for creation of green pesticides with a novel functional mechanism.
Description
Technical field
The present invention relates to a kind of bridged piperazine derivatives and uses thereof, specifically, relate to a kind of N
1-(replacement) arylmethyl, N
4-substituted pyridinyl piperazine and uses thereof.
Background technology
Sterilant is one type of important agricultural chemicals, in agriculture prodn, plays important effect.Along with the puzzlement of the public to the resistance problem of the growing interest of the environment protection and the eubiosis and existing agricultural chemicals, it is urgent day by day that initiative has the green pesticide of new role mechanism.
Serotonin is one type of very important alkamines neurotransmitter, can participate in regulating vertebrate many important physiological activities through acting on the serotonin acceptor.So serotonin can have important pharmacological significance at field of medicaments by part.
Research shows: serotonin also is a neurotransmitter important in the insect body simultaneously, and its acceptor is distributed widely in the maincenter and the peripheral nervous system of insect body, and that participates in regulating insect gets important physical function and behaviors such as food, reproduction, diel rhythm and defence.And because there are homology difference in vertebrates serotonin acceptor and non-vertebrates serotonin acceptor, so also inevitable difference to some extent between its part.Thereby the research of insect serotonin ability part not only has great significance to insect physiology, also is that the initiative of the green pesticide of highly selective new role mechanism provides a new direction simultaneously.And the technical issues that need to address of the present invention are to search out and the corresponding ligand compound of insect serotonin acceptor, use it for the regulation and control insect's food-taking, growth, and physiological function such as reproduction or cause insect death, thus play the effect of plant protection.
Summary of the invention
The contriver thinks that through structure and activity research to existing vertebrates serotonin part the aryl substituted-piperazinyl can be used as the probe of research insect serotonin acceptor.Aryl substituted-piperazinyl analog derivative is one type of dark vertebrates serotonin ability part of being paid close attention to and being studied extensively and profoundly.It is generally believed it is the most general structure masterplate (Glennon, the R.A. of research serotonin acceptor; Naiman, N.A.; Lyon, R.A.; Titerler, M.Arylpiperazine derivatives as high-affinity 5-HT
1ASerotonin ligands.J.Med.Chem.1988,31,1968-1971, Glennon, R.A.Concepts for the design of5-HT
1ASerotonin agonists and antagonists.Drug Dev.Res.1992,26,251-274, Glennon, R.A.; Dukat, M.5-HT receptor ligands-update 1992.Curr. Drugs:Serotonin 1992,1-45).
The present invention is with N
1-arylmethyl, N
4-pyridyl piperazine is a parent, and the structure of its main pharmacodynamics group type of carrying out agricultural chemicals is modified, and obtains one type of new compound.The bioassay showed that: the present invention to design and synthesize new compounds can effectively inhibit Lin Hymenoptera insect feeding, growth and lead to their death.This not only helps the further research of insect serotonin acceptor, and is that the initiative of the environment friendly agricultural of one type of new role mechanism provides direction.
One of the object of the invention is, a kind of new bridged piperazine derivatives is provided;
Two of the object of the invention is, a kind of purposes of above-mentioned bridged piperazine derivatives is provided.
The said bridged piperazine derivatives of the present invention, it has structure shown in the formula (I):
In the formula (I): R
1, R
2, R
3And R
4Be selected from hydrogen, C respectively
1～C
6A kind of in perfluoroalkyl or the halogen (F, Cl, Br or I), and R
1, R
2, R
3And R
4In must have and only have one for C
1～C
6Perfluoroalkyl; A is C
5～C
10Aromatic ring yl, substituted C
5～C
10Aromatic ring yl, C
3～C
8Aromatic heterocyclic or substituted C
3～C
8Aromatic heterocyclic; M is 0 or 1;
Wherein: said substituted C
5～C
10Aromatic ring yl and substituted C
3～C
8Substituting group in the aromatic heterocyclic is selected from halogen (F, Cl, Br or I), amino or C
1～C
6Halogen (F, Cl, Br or I) for one or more (to replacement quantity) in the alkyl with reasonable chemical implication; Said C
3～C
8Aromatic heterocyclic and substituted C
3～C
8Heteroatoms in the aromatic heterocyclic is selected among N, S and the O one or both.
In an optimal technical scheme of the present invention, R
1, R
2, R
3And R
4Be selected from hydrogen, C respectively
1～C
3A kind of in perfluoroalkyl or the halogen (F, Cl, Br or I), and R
1, R
2, R
3And R
4In must have and only have one for C
1～C
3Perfluoroalkyl; Preferred R
1, R
2, R
3And R
4Be selected from respectively in hydrogen, trifluoromethyl or the halogen (F, Cl, Br or I) a kind of, and R
1, R
2, R
3And R
4In must have and only have one for trifluoromethyl;
In another optimal technical scheme of the present invention, A is five yuan or hexa-atomic aromatic ring yl, substituted five yuan or hexa-atomic aromatic ring yl, five yuan or hexa-atomic aromatic heterocyclic or substituted five yuan or hexa-atomic aromatic heterocyclic,
Wherein: the substituting group in said substituted five yuan or hexa-atomic aromatic ring yl and the aromatic heterocyclic is selected from halogen (F, Cl, Br or I), or C
1～C
3Halogen (F, Cl, Br or I) substituted alkyl in one or more (to replacement quantity) with reasonable chemical implication; Heteroatoms in said five yuan or hexa-atomic aromatic heterocyclic and substituted five yuan or the hexa-atomic aromatic heterocyclic is selected among N, S and the O one or both.
Embodiment
The synthetic route of the synthetic said bridged piperazine derivatives of the present invention is as follows:
Wherein: A, R
1, R
2, R
3And R
4Implication said identical with preamble; X is halogen (F, Cl, Br or I), and preferred X is Cl or Br.
For ease of narration, hereinafter: compound shown in the formula B is called for short compd B, and all the other by that analogy.
Prepare the method for the said bridged piperazine derivatives of the present invention, comprise the steps:
(1) with compd B (like A-CH
2-Cl) be raw material, anhydrous monohydroxy-alcohol is (like C
1～C
3Monohydroxy-alcohol) be that solvent, alkylamine (like triethylamine) are acid binding agent, with Piperazine anhydrous (Compound C) react Compound D;
(2) Compound D and compd E are placed aprotic polar solvent (like acetonitrile), make compound F 17-hydroxy-corticosterone (one of target compound) through condensation reaction at (under the Anhydrous potassium carbonate existence condition) under the alkaline condition;
(3) oxygenated compound F (as adopting the metachloroperbenzoic acid oxidation) gets two (compound G) of target compound.
Through embodiment the present invention is described further below, its purpose only is better understanding content of the present invention, and unrestricted protection scope of the present invention:
Embodiment 1
(the 5-5-flumethiazine-2-) piperazine is synthetic for 1-(6-chloropyridine-3-methyl)-4-
(1) 1-(6-chloropyridine-3-methyl) piperazine is synthetic:
Reaction equation is following:
10ml ethanol solution with the 6-chloro-3-PMC of 1.61g (10mmol); Under 50～55 ℃ of oil baths; Slowly splash in the 15ml ethanol solution that is dissolved with 1.32g (15mmol) Piperazine anhydrous and 10mmol triethylamine; System stirred 5～6 hours, and raw material 6-chloro-3-PMC reacts completely.Steaming desolventizes ethanol and obtains thick product, through washing, dichloromethane extraction and anhydrous Na
2SO
4Drying, the pressure reducing and steaming solvent gets straight product, and yield is about 86%,
GC/MS(m/s)211(38)M
+，169(100)，126(78)，56(23)。
(2) 1-(6-chloropyridine-3-methyl)-4-(piperazine of 5-5-flumethiazine-2-) synthetic:
Reaction equation is following:
1-(6-chloropyridine-3-methyl) piperazine (2.13g) Deng mole (1mmol); 2-chloro-5-5-flumethiazine (1.81g) and Anhydrous potassium carbonate (1.38g) in the 20ml acetonitrile, about 45 ℃ stirrings of maintenance system temperature, TLC follows the tracks of; React after 5～6 hours, the raw material point reacts completely.Reaction mixture is poured in the water, and with ethyl acetate extraction three times, combining extraction liquid is with saturated brine and washing, anhydrous sodium sulfate drying.Behind the pressure reducing and steaming solvent, get thick product and use column chromatography product, (v/v=4: 1) wash-out, the pressure reducing and steaming solvent gets yellow solid, productive rate about 73% to petrol ether/ethyl acetate.mp：88-89℃。
IR(KBr)υ
max(cm
-1)：2806，1606，1500，1374，1118，817；
1H NMR (500MHz, CDCl
3) δ (ppm): 2.54 (m, 4H, pip-H), 3.54 (s, 2H, CH
2), 3.66 (m, 4H, pip-H), 6.64 (d, J=9.02Hz, 1H, Py-H), 7.34 (m, 1H, Py-H), 7.62 (dd, J
1=2.25Hz, J
2=2.24 Hz, 1H, Py-H), 7.70 (dd, J
1=2.25Hz, J
2=2.29Hz, 1H, Py-H), 8.34 (s, 1H, Py-H), 8.38 (s, 1H, Py-H); EIMS, m/z (%) 356 (M
+, 12), 337 (7), 230 (10), 194 (28), 175 (100), 147 (25), 126 (67), 56 (23) .HRMS for C
16H
16ClF
3N
4: calculated value (calcd) [M
+], 356.1016; Experimental value (found), 356.1037.
Embodiment 2
Peroxo-1-(6-chloropyridine-3-methyl)-4-(the 5-5-flumethiazine-2-) piperazine is synthetic,
Reaction equation is following:
In ice bath, (add 1mmol metachloroperbenzoic acid (MCPBA) at twice in the 20ml dichloromethane solution of the piperazine of 5-5-flumethiazine-2-) to being dissolved with 1mmol 1-(6-chloro-pyridine-3-methyl)-4-.Then, reaction system at room temperature stirs, and TLC follows the tracks of, and reacts after 12 hours, and the raw material point reacts completely.Reaction mixture is poured in the water, with dichloromethane extraction three times, merges organic phase, with saturated brine and washing, anhydrous sodium sulfate drying.Behind the pressure reducing and steaming solvent, get thick product and use column chromatography product, (v/v=8: 1) wash-out, the pressure reducing and steaming solvent gets red solid, productive rate about 63% to methylene dichloride/ethanol.mp：66-68℃；
IR(KBr)υ
max(cm
-1)：3368，2899，1611，1329，1108，811，775；
1H?NMR(500MHz，CDCl
3)δ(ppm)：3.22(d，J＝10.84Hz，2H，pip-H)，3.33(m，2H，pip-H)，3.92(m，2H，pip-H)，4.30(d，J＝14.11Hz，2H，pip-H)，4.41(s，2H，CH
2)，6.72(d，J＝8.99?Hz，1H，Py-H)，7.44(d，J＝8.15Hz，1H，Py-H)，7.70(dd，J
1＝2.27Hz，J
2＝2.33Hz，1H，Py-H)，8.19(dd，J
1＝2.12Hz，J
2＝2.22Hz，1H，Py-H)，8.43(d，J＝1.59Hz，1H，Py-H)；
HRMS (ESI) for C
16H
16ClF
3N
4O calculated value (calcd) [M+H
+], 373.1043; Experimental value (found) 373.1040.
Embodiment 3
(3-chloro-5-5-flumethiazine-2-) piperazine is synthetic for 1-(2-diuril azoles-5-methyl)-4-
(1) 1-(2-diuril azoles-2-methyl) piperazine is synthetic
Reaction equation is following:
10ml ethanol solution with the 2-chloro-5-5-chloromethyl thiazole of 1.67g (10mmol); Under oil bath 50-55 ℃; Slowly splash in the 15ml ethanol solution that is dissolved with 1.32g (15mmol) Piperazine anhydrous and 10mmol triethylamine; System stirred 5-6 hour, and the 2-chloro-5-5-chloromethyl thiazole of raw material 1.67g (10mmol) reacts completely.Steaming desolventizes ethanol and obtains thick product, through washing, dichloromethane extraction and anhydrous Na
2SO
4Drying, the pressure reducing and steaming solvent gets straight product, yield about 87%.
GC/MS(m/s)217(44)M
+，175(79)，132(100)，56(31)。
(2) 1-(2-diuril azoles-5-methyl)-4-(3-chloro-5-5-flumethiazine-2-) the building-up reactions equation of piperazine is following:
Equimolar 1-(2-diuril azoles-2-methyl) piperazine (2.17g), 2,3-two chloro-5-trifluoromethyl piperazine pyridines (2.15g) and Anhydrous potassium carbonate (1.38g) are in the 20ml acetonitrile; About 45 ℃ stirrings of maintenance system temperature; TLC follows the tracks of, and reacts after 5-6 hour, and the raw material point reacts completely.Reaction mixture is poured in the water, and with ethyl acetate extraction three times, combining extraction liquid is with saturated brine and washing, anhydrous sodium sulfate drying.Behind the pressure reducing and steaming solvent, get thick product and use column chromatography product, (v/v=4: 1) wash-out, the pressure reducing and steaming solvent gets yellow viscous liquid, productive rate about 72% to petrol ether/ethyl acetate.
IR(KBr)υ
max(cm
-1)：2823，1597，1316，1126，750；
1H?NMR(500MHz，CDCl
3)δ(ppm)：2.65(m，4H，pip-H)，3.53(m，4H，pip-H)，3.72(s，1H，CH
2)，7.38(s，1H，thiazol-H)，7.75(s，1H，Py-H)，8.39(s，1H，Py-H)；
EIMS, m/z (%) 396 (M
+, 7), 361 (24), 237 (4), 223 (29), 209 (76), 187 (53), 175 (11), 165 (33), 153 (10), 145 (16), 131 (100), 56 (21) .HRMS for C
14H
13Cl
2F
3N
4S: calculated value (calcd) [M
+], 396.0190; Experimental value (found), 396.0200.
Embodiment 4
(3-chloro-5-5-flumethiazine-2-) piperazine is synthetic for peroxo-1-(2-diuril azoles-5-methyl)-4-
Reaction equation is following:
Except that raw material is that (the piperazine of 3-chloro-5-5-flumethiazine-2-), all the other preparing methods are identical with embodiment 2 for 1-(2-diuril azoles-5-methyl)-4-.Obtaining pure article through column chromatography for separation is yellow powder shape solid, and productive rate is 62%.mp：149-151℃；
IR(KBr)υ
max(cm
-1)：3416，2947，1597，1314，1123，850，763；
1H?NMR(500MHz，CDCl
3)δ(ppm)：3.34(d，J＝10.63Hz，2H，pip-H)，3.46(m，2H，pip-H)，4.00(d，J＝6.49Hz，2H，pip-H)，4.64(s，1H，CH
2)，7.58(s，1H，thiazol-H)，7.82(d，J＝2.02Hz，1H，Py-H)，8.43(d，J＝1.08Hz，1H，Py-H)；
HRMS (ESI) for C
14H
13Cl
2F
3N
4OS calculated value (calcd) [M+H
+], 413.0217; Experimental value (found) 413.0219.
Embodiment 5
((6-chloro-3-5-flumethiazine-2-) piperazine is synthetic for the piperazine of 6-chloro-5-5-flumethiazine-2-) and 1-(2-chlorophenylmethyl)-4-for 1-(2-chlorophenylmethyl)-4-
(1) 1-(2-benzyl chloride base) piperazine is synthetic:
Reaction equation is following:
Except that raw material was adjacent chlorobenzyl chloride, all the other preparing methods were identical with embodiment 1.The pressure reducing and steaming solvent gets faint yellow solid, and yield is about 85%, GC/MS (m/s) 210 (46) M
+, 168 (72), 125 (100), 56 (13).
(2) 1-(2-chlorophenylmethyl)-4-(piperazine of 6-chloro-5-5-flumethiazine-2-) and 1-(2-chlorophenylmethyl)-4-(6-chloro-3-5-flumethiazine-2-) piperazine is synthetic:
Reaction equation is following:
Equimolar 1-(2-chlorophenylmethyl) piperazine (2.12g); 2,6-two chloro-5-trifluoromethyl piperazine pyridines (2.15g) and Anhydrous potassium carbonate (1.38g) in the 20ml acetonitrile, about 45 ℃ stirrings of maintenance system temperature; TLC follows the tracks of; React after 5-6 hour, the raw material point reacts completely, and reaction system has 1-(2-chlorophenylmethyl)-4-(piperazine (R of 6-chloro-5-5-flumethiazine-2-)
f=0.6) and 1-(2-chlorophenylmethyl)-4-(piperazine (R of 6-chloro-3-5-flumethiazine-2-)
f=0.4) generates simultaneously.Reaction mixture is poured in the water, and with ethyl acetate extraction three times, combining extraction liquid is with saturated brine and washing, anhydrous sodium sulfate drying.Behind the pressure reducing and steaming solvent; Get thick product and use column chromatography product, petrol ether/ethyl acetate (v/v=4: 1) wash-out, pressure reducing and steaming solvent; Yellow viscous liquid, 1-(the 2-chlorophenylmethyl)-4-(productive rate of piperazine about 49% of 6-chloro-5-5-flumethiazine-2-).
IR(KBr)υ
max(cm
-1)：2806，1593，1325，1251，1113，750；
1H?NMR(500MHz，CDCl
3)δ(ppm)：2.60(m，4H，pip-H)，3.66(m，6H，CH
2，pip-H)，6.46(d，J＝8.78Hz，1H，Py-H)，7.24(m，2H，Ar-H)，7.37(m，1H，Ar-H)，7.50(d，J＝7.23Hz，1H，Ar-H)，7.66(d，J＝8.81Hz，1H，Py-H)；
EIMS, m/z (%) 389 (M
+), 223 (4), 209 (12), 180 (86), 168 (28), 125 (100), 89 (6), 69 (10), 56 (19) .HRMS for C
17H
16Cl
2F
3N
3: calculated value (calcd) [M
+], 389.0673; Experimental value (found), 389.0700.
1-(2-chlorophenylmethyl)-4-(piperazine (yellow viscous liquid) of 6-chloro-3-5-flumethiazine-2-), yield about 24%.
IR(KBr)υ
max(cm
-1)：2826，1587，1302，1103，759；
1H?NMR(500MHz，CDCl
3)δ(ppm)：2.65(m，4H，pip-H)，3.45(m，4H，pip-H)，3.69(s，2H，CH
2)，6.88(d，J＝7.98Hz，1H，Py-H)，7.23(m，2H，Ar-H)，7.36(m，1H，Ar-H)，7.53(m，1H，Ar-H)，7.74(d，J＝8.07Hz，1H，Py-H)；
EIMS, m/z (%) 389 (M
+, 12), 223 (4), 209 (12), 180 (86), 168 (28), 125 (100), 89 (6), 69 (10), 56 (19) .HRMS for C
17H
16Cl
2F
3N
3: calculated value (calcd) [M
+], 389.0673; Experimental value (found) 389.0700.
Embodiment 6
The present invention designs and the insecticidal activity of synthetic compound is tested.
Instruction through embodiment part (comprising embodiment 1～5) said method also can prepare other compound (except that embodiment 1～5 described compound) of general formula (I) expression, and prepared all compounds are carried out the insecticidal activity test.
The present invention Select armyworm (Pseudaletia? Separate? Walker) - belongs to Lin Hymenoptera, size small soft chewing is a common crop pests - for the test object, the World Health Organization (WHO) recommended impregnation method to test determine the insecticidal activity of the test compound, the results are shown in Table 1, Table 1 is 500ppm compound armyworm (Pseudaletia? Separate? Walker) growth inhibitory activity and death.
Concrete test operating procedure: the accurate various samples of weighing; Add DMSO 99.8MIN. (DMSO) 2ml and 18ml clear water respectively; Add three emulsifying agent 220I (Shanghai insecticide factory provides) again and be made into soup, blank with DMSO 2ml and 28ml clear water, add three emulsifying agent 220I and be made into.
The tender seedling of corn of 2-3 leaf phase is got into respectively in the above-mentioned soup that has prepared, treat that blade soaks into fully after, taking-up is dried, it is subsequent use to cut off blade (length is 5cm).Support and insert 2 10 of armyworms in age (after taking by weighing polypide weight) in the scolite, above-mentioned impregnated blade is put into foster scolite, mouth mask is lived (every concentration triplicate) with gauze.The death state of 72 hours inspection examination worms.Body weight suppresses test: for reducing experimental error, this experiment adopts secondary to supply the medicine method, and 72h adds the blade that single-steeping is crossed soup again.Keeping temperature in the experimentation is 22-27 ℃, and humidity is 70%～80%, and 120h takes by weighing each foster scolite polypide weight.In medication 2-5 days inspection larval mortalities (death standard touches polypide with hard thing, and motionless person is dead).Below 5%, each is handled mortality ratio and needn't proofread and correct as if blank mortality ratio in the back.Give birth to the survey result and see table 1:
Growth inhibition ratio (%)=[(120h contrast polypide weight-contrast polypide weight)-(polypide weight before the weight-administration of 120h administration polypide)]/(120h contrast polypide weight-contrast polypide weight)
In table 1, corrected mortality (%) abbreviates mortality ratio (%) as.
Table 1
Claims (8)
1. bridged piperazine derivatives, it has structure shown in the formula (I):
In the formula (I): R
1, R
2, R
3And R
4Be selected from hydrogen, C respectively
1～C
6A kind of in perfluoroalkyl or the halogen, and R
1, R
2, R
3And R
4In must have and only have one for C
1～C
6Perfluoroalkyl; A is C
3～C
8Aromatic heterocyclic or substituted C
3～C
8Aromatic heterocyclic; M is 0 or 1;
Wherein: said substituted C
3～C
8Substituting group in the aromatic heterocyclic is selected from halogen, amino or C
1～C
6The halo alkyl in one or more; Said C
3～C
8Aromatic heterocyclic and substituted C
3～C
8Heteroatoms in the aromatic heterocyclic is selected among N, S and the O one or both.
2. bridged piperazine derivatives as claimed in claim 1 is characterized in that, wherein R
1, R
2, R
3And R
4Be selected from hydrogen, C respectively
1～C
3A kind of in perfluoroalkyl or the halogen, and R
1, R
2, R
3And R
4In must have and only have one for C
1～C
3Perfluoroalkyl.
3. bridged piperazine derivatives as claimed in claim 2 is characterized in that, wherein R
1, R
2, R
3And R
4Be selected from respectively in hydrogen, trifluoromethyl or the halogen a kind of, and R
1, R
2, R
3And R
4In must have and only have one for trifluoromethyl.
4. bridged piperazine derivatives as claimed in claim 3 is characterized in that, wherein A is five yuan or hexa-atomic aromatic heterocyclic or substituted five yuan or hexa-atomic aromatic heterocyclic.
5. bridged piperazine derivatives as claimed in claim 4 is characterized in that, the substituting group in wherein said substituted five yuan or the hexa-atomic aromatic heterocyclic is selected from halogen, or C
1～C
3Haloalkyl in one or more.
6. bridged piperazine derivatives as claimed in claim 5; It is characterized in that said bridged piperazine derivatives is 1-(6-chloropyridine-3-methyl)-4-(piperazine of 5-5-flumethiazine-2-), peroxo-1-(6-chloropyridine-3-methyl)-4-(piperazine of 5-5-flumethiazine-2-), 1-(the 2-diuril azoles-5-methyl)-4-(piperazine of 3-chloro-5-5-flumethiazine-2-) or peroxo-1-(2-diuril azoles-5-methyl)-4-(3-chloro-5-5-flumethiazine-2-)-piperazine.
7. a bridged piperazine derivatives is characterized in that, said bridged piperazine derivatives is: 1-(the 2-chlorophenylmethyl)-4-(piperazine of 6-chloro-5-5-flumethiazine-2-) or 1-(the 2-chlorophenylmethyl)-4-(piperazine of 6-chloro-3-5-flumethiazine-2-).
As claimed in any of claims 1 to 7, wherein a preparation of a piperazine derivative Lin Orthoptera inhibiting feeding, growth and death of the medicament resulting in the application.
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| CN104418800B (en) * | 2013-09-06 | 2017-06-16 | 沈阳中化农药化工研发有限公司 | Aryl pyrrole (phonetic) pyridine class compound and application thereof |
| CN106316931B (en) * | 2015-07-10 | 2020-05-05 | 沈阳中化农药化工研发有限公司 | 2-phenylnicotinic acid derivatives with insecticidal and acaricidal activity |
| CN106674211A (en) * | 2015-11-06 | 2017-05-17 | 江苏先声药业有限公司 | Noxafil impurities and preparation methods thereof |
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| Michalik, Dirk et al.A short and efficient synthesis of N-aryl- and N-heteroaryl-N"-(arylalkyl)piperazines.《Tetrahedron Letters》.2004,第45卷(第10期),2058. * |
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