CN102827145B - Novel deuterated o-aminobenzamide compound, and preparation method and application thereof - Google Patents
Novel deuterated o-aminobenzamide compound, and preparation method and application thereof Download PDFInfo
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- CN102827145B CN102827145B CN201210342813.XA CN201210342813A CN102827145B CN 102827145 B CN102827145 B CN 102827145B CN 201210342813 A CN201210342813 A CN 201210342813A CN 102827145 B CN102827145 B CN 102827145B
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- 0 Cc(cc1C(*)=O)cc(*)c1NC(c1cc(*)n[n]1-c1c(*)cccn1)=O Chemical compound Cc(cc1C(*)=O)cc(*)c1NC(c1cc(*)n[n]1-c1c(*)cccn1)=O 0.000 description 10
Abstract
The invention provides a compound shown as a formula I, wherein R1 is CH3, F, Cl or Br; R2 is F, Cl, Br, I, -CN or CF3; R3 is CF3, Cl, Br or OCH2CF3; R4 is Cl or Br; and X is an integer within 0-2 and X+Y=3. The compound has a better pesticide effect of preventing and controlling invertebrate pests and longer effective duration. Since the pesticide effect is improved, the application amount during use is reduced, the toxicity to non-target organisms is reduced, the safety is improved and the environmental pollution caused by residue pesticide is reduced. The invention additionally provides a preparation method of the compound and application to prevention and control of invertebrate pests.
Description
Technical field
The present invention relates to a kind of compound, be specifically related to a kind of deuterated Anthranilamide compound, and with this compound, prevent and treat invertebrate pests as arthropodan method in agricultural and non-agricultural environment.
Background technology
Invertebrate pests as arthropodan control in realizing the process of high-efficiency agriculture, be very important.Invertebrate pests to growing with store after the harm of farm crop can cause Severe Reduction, thereby increase human consumer's expense.The control of invertebrate pests is in forest, chamber crop, ornamental plant, nursery crop, storing food and fiber product, domestic animal, family life, and in public health and animal health, is also important.Although now can buy many products for above-mentioned purpose, still need more effective, cheap, low toxicity, environmentally safe or there is the new compound of the different modes of action.
NL9202078 discloses the N-acyl anthranilic acid derivative as sterilant, and structure is as follows:
Wherein, especially, X is direct key; Y is H or C1-C3 alkyl; Z is NH
2, NH (C1-C3 alkyl) or N (C1-C3 alkyl); And R
1to R
2each is H, halogen, C1-C3 naturally, alkyl, phenyl, hydroxyl, C1-C3 alkoxyl group or C1-C3 acyloxy.
Du pont company is texture improvement in addition on this basis; successfully developed sterilant Rynaxypyr (Chlorantraniliprole; the bromo-N-[4-chloro-2-methyl-6-[(of chemical name 3-methyl-carbamoyl) benzene]-1-(3-chloropyridine-2-yl)-1H-pyrazoles-5-methane amide), and commercial applications.
Yet we find, when some hydrogen atoms in this compounds are partly or entirely replaced by deuterium, to have more high reactivity in research process.
The important feature of deuterium is that its shape in drug molecule and volume and hydrogen are basic identical.That is to say, the hydrogen in drug molecule is by the deuterium that replaces with of selectivity, and deuterated medicine generally can retain biological activity and the selectivity of original medicine.But carbon-deuterium is strong more stable than hydrocarbon key, carries the frequency vibrations that the deuterium of neutron and the carbon-deuterium of carbon formation are alive lower, thereby be better than hydrocarbon key.The increase of this intensity can directly affect the attributes such as absorption, distribution, metabolism and excretion of medicine, thereby improves curative effect, security and the tolerance of medicine.Therefore theory is thought, if some the specific C-Hs by being decomposed in drug molecule deuterated for carbon-deuterium strong after, will delay its decomposition course, make deuterated medicine longer action time in vivo, effect is better than original medicine.
Researchist's discovery of the present invention, the reactive hydrogen in a class benzamide in part methyl, by after deuterated, has the control invertebrate pests drug effect higher than former compound, and efficiency time is longer.Can reduce refuse in building-up process like this, with entering because drug effect improves, reduce amount of application in use, thereby reduce the toxicity to non-target organism, improve security, reduce the pollution of left drug to environment.
Researchist of the present invention believes, along with further deeply making progress of research, the relative perhydro-compound of the deuterated benzamide Pesticidal compound of this class in technical solution of the present invention, in environmental toxicity, security, can be found successively to the more advantage of the active aspect of some particular target insects.
Summary of the invention
Based on above-mentioned technical background, the invention provides a kind of new benzamide compound, the corresponding deuterated compound of this compound was not than having in the past deuterated benzamide compounds to have higher control invertebrate pests active, and the present invention simultaneously also provides synthetic method and the application of this deuterated compound.
Above-mentioned purpose of the present invention is achieved through the following technical solutions:
Compound shown in a kind of formula I is provided
Wherein, R
1cH
3, F, Cl or Br; R
2f, Cl, Br, I ,-CN or CF
3; R
3cF
3, Cl, Br or OCH
2cF
3; R
4cl or Br; X gets 0 ~ 2 integer, and X+Y=3.
Benzamide compound of the present invention, when X corresponds to the compound of following formula II ~ (IV) at 0,1,2 o'clock
In view of cost, be convenient to the factors such as synthetic and/or biological activity, R in preferred structure of the present invention
4be the compound of Cl, be denoted as preferably 1.
In described preferably 1 compound, further R in preferred structure
3be the compound of Cl or Br, be denoted as preferably 2.
In described preferably 2 compound, further R in preferred structure
2be the compound of Cl ,-CN or Br, be denoted as preferably 3.
In described preferably 3 compound, further R in preferred structure
1cH
3or the compound of Cl, be denoted as preferably 4.
The compound of formula I of the present invention, specifically can be preferably any one in following compound:
The compound of formula I, wherein R
1cH
3, R
2br, R
3cF
3and R
4cl, X=0 Y=3;
The compound of formula I, wherein R
1cH
3, R
2br, R
3cF
3and R
4cl, X=2 Y=1;
The compound of formula I, wherein R
1cH
3, R
2br, R
3br and R
4cl, X=0 Y=3;
The compound of formula I, wherein R
1cH
3, R
2br, R
3br and R
4cl, X=2 Y=1;
The compound of formula I, wherein R
1cH
3, R
2br, R
3cl and R
4cl, X=0 Y=3;
The compound of formula I, wherein R
1cH
3, R
2br, R
3cl and R
4c1, X=2 Y=1;
The compound of formula I, wherein R
1cH
3, R
2cl, R
3cF
3and R
4c1, X=0 Y=3;
The compound of formula I, wherein R
1cH
3, R
2cl, R
3cF
3and R
4c1, X=2 Y=1;
The compound of formula I, wherein R
1cH
3, R
2cl, R
3br and R
4cl, X=0 Y=3;
The compound of formula I, wherein R
1cH
3, R
2cl, R
3br and R
4cl, X=1 Y=2;
The compound of formula I, wherein R
1cH
3, R
2cl, R
3br and R
4cl, X=2 Y=1;
The compound of formula I, wherein R
1cH
3, R
2cl, R
3cl and R
4cl, X=0 Y=3;
The compound of formula I, wherein R
1cH
3, R
2cl, R
3cl and R
4c1, X=2 Y=1;
The compound of formula I, wherein R
1cH
3, R
2cl, R
3oCH
2cF
3and R
4c1, X=0 Y=3;
The compound of formula I, wherein R
1cH
3, R
2cl, R
3oCH
2cF
3and R
4c1, X=2 Y=1;
The compound of formula I, wherein R
1cH
3, R
2be-CN, R
3br and R
4cl, X=0 Y=3;
The compound of formula I, wherein R
1cH
3, R
2be-CN, R
3br and R
4cl, X=1 Y=2; Or
The compound of formula I, wherein R
1cH
3, R
2be-CN, R
3br and R
4c1, X=2 Y=1.
The most preferred compound of the present invention is 6 compounds as shown in following formula (V)-(X):
Compound of the present invention can one or more steric isomers form exist.Various steric isomers comprise enantiomer, diastereomer, atropisomer and geometrical isomer.Those skilled in the art will recognize that when a kind of steric isomer more or when separating from other isomer with respect to other content of isomer, this isomer can demonstrate higher active and/or show favourable effect.In addition, how those skilled in the art also know separated, the concentrated and/or described steric isomer of preparation optionally.Therefore, the present invention includes compound or the upper applicable salt of its agricultural of formula 1.The compounds of this invention can steric isomer mixture, single steric isomer, or exist with optic active body form.
The present invention also provides the applicable salt in agricultural of the compound shown in a kind of formula I.
Described applicable salt in agricultural is the acid salt of the compound shown in formula I.Described acid can be mineral acid or organic acid.Described mineral acid can be selected from Hydrogen bromide, spirit of salt, nitric acid, phosphoric acid or sulfuric acid; Described organic acid can be selected from acetic acid, butyric acid, fumaric acid, lactic acid, toxilic acid, propanedioic acid, oxalic acid, propionic acid, Whitfield's ointment, tartrate, 4-toluenesulphonic acids or valeric acid.
The present invention also provides two kinds of preparation methods of described compound.
The first preparation method comprises the following steps:
1, deuterated methanol is through the synthetic deuterated methylamine of ammonification, and deuterated methylamine and substituted aroma phenylformic acid obtain substituted aroma benzamide through amination; Reaction process is as follows, wherein R
1cH
3, F, Cl or Br; X gets 0 ~ 2 integer, and X+Y=3;
2, substituted aroma benzamide is through the synthetic Halogen substituted aroma benzamide of halogenation; Reaction process is as follows, wherein R
1define the same; R
2f, Cl, Br, I ,-CN or CF
3; X gets 0 ~ 2 integer, and X+Y=3;
3, the synthetic hydrazino pyridine that replaces of substituted pyridines and hydrazine, then generates substituted pyridinyl pyrazoline with maleic acid ester cyclization; Reaction process is as follows, wherein R
4cl or Br;
4, the hydroxyl of substituted pyridinyl pyrazoline is halogenated synthesizing halogen pyridyl pyrazoline, halogenated pyridyl pyrazoline dehydrogenation synthesizing halogen pyridyl pyrazoles; Reaction process is as follows, wherein R
3cF
3, Cl, Br or OCH
2cF
3; R
4define the same;
5, the deuterated Anthranilamide compound of the pyrazole-fused generation object of halogenated pyridyl product that the Halogen substituted aroma benzamide that step 2 obtains and step 4 obtain; Reaction process is as follows, wherein R
1, R
2, R
3, R
4, X and Y definition the same.
The second is preparation method comprise the following steps:
1, deuterated methanol is through the synthetic deuterated methylamine of ammonification, and reaction formula is as follows, and wherein X gets 0 ~ 2 integer, and X+Y=3;
2, the acid of substituted pyridinyl pyrazoles and the synthetic benzoxazine ketone compounds of the aminobenzoic acid-respons replacing, reaction process is as follows, wherein R
1cH
3, F, Cl or Br; R
2f, Cl, Br, I ,-CN or CF
3; R
3cF
3, Cl, Br or OCH
2cF
3; R
4cl or Br;
3, in the deuterated methylamine synthesizing in step 1 and step 2, synthetic benzoxazine ketone compounds reaction obtains the deuterated Anthranilamide compound of formula (I), and reaction process is as follows, wherein R
1, R
2, R
3, R
4, X and Y definition with step 1 and step 2.
In above method, all starting compounds are all existing compounds, or can prepare by existing method.
The present invention also provides a kind of composition of preventing and treating invertebrate pests, the upper applicable salt of the compound shown in the formula I that it contains biologic effective dose or its agricultural and be selected from one or more other components in tensio-active agent, solid diluent or liquid diluent.
In described agricultural, applicable salt is the acid salt of the compound shown in formula I.Described acid can be selected from Hydrogen bromide, spirit of salt, nitric acid, phosphoric acid or sulfuric acid, acetic acid, butyric acid, fumaric acid, lactic acid, toxilic acid, propanedioic acid, oxalic acid, propionic acid, Whitfield's ointment, tartrate, 4-toluenesulphonic acids or valeric acid.
Composition of the present invention can also further contain at least one other biological active compound or preparation.
Described at least one other biological active compound or preparation are selected from following arthropodicide: the macrolide of pyrethroid, amino formate, class nicotinoids, neural sodium channel blockers, desinsection, γ-aminobutyric acid antagonist, desinsection ureas or neotonin stand-in.Their specific examples comprises Avermectin, acephate, acetamiprid, amidoflumet, Avrmectin, nimbin, methyl R-1582, bifenthrin, Bifenazate, Buprofezin, Furadan, Chlorfenapyr, fluorine pyridine urea, Chlorpyrifos 94, chlorpyrifos_methyl, ring worm hydrazides, clothianidin, cyfloxylate, betacyfluthrin, cyhalothrin, lambda-cyhalothrin, Cypermethrin, cyromazine, Deltamethrin, diafenthiuron, diazinon, diflubenzuron, Rogor, difenolan, Affirm (Merck Co.), 5a,6,9,9a-hexahydro-6,9-methano-2,4, efficient fenvalerate, ethiprole, fenothiocarb, fenoxycarb, Fenvalerate, fenvalerate, ethiprole, flonicamid, flucythrinate, taufluvalinate, flufenerim, flufenoxuron, Dyfonate, chlorine worm hydrazides, HEXAFLUMURON, Provado, oxadiazoles worm, propylamine phosphorus, lufenuron, Malathion, Halizan, acephatemet, methidathion, methomyl, Entocon ZR 515, methoxychlor, monocrotophos, methoxyfenozide, WL 35651, Rimon, noviflumuron, thioxamyl, thiophos, parathion-methyl, permethrin, phorate, Phosalone, R-1504, phosphamidon, Aphox, Profenofos, pymetrozine, pyridalyl, pyriproxyfen, tubatoxin, pleocidin, spitomesifin, sulprofos, worm hydrazides, Teflubenzuron, tefluthrin, terbufos, tetrachlorvinphos, thiacloprid, Diacloden, thiodicarb, disosultap, tralomethrin, Trichlorphon, desinsection is grand, aldicarb, thioxamyl, Nemacur, amitraz, kill mite violent, G-23922, cyhexatin, Mitigan, Hooker HRS 16, second mite azoles, fenazaquin, fenbutatin oxide, fenpyroximate, hexythiazox, propargite, pyridaben or tebufenpyrad, or biotechnological formulation.
Described biotechnological formulation is selected from insect malignant bacteria, virus and fungi; Described insect malignant bacteria is preferably from the delta-endotoxin of Su Yun gold bar mattress aizawai mutation, Bacillus thuringiensis kurstaki mutation or Bacillus thuringiensis packing; And described insect pathogenic virus is the baculovirus of desinsection.
At least one above-mentioned other biological active compound or preparation are more preferably from following sterilant, nematocides, miticide or biotechnological formulation, comprise Cypermethrin, cyhalothrin, cyfloxylate, betacyfluthrin, efficient fenvalerate, fenvalerate, tralomethrin, fenothiocarb, methomyl, thioxamyl, thiodicarb, clothianidin, Provado, Diacloden, oxadiazoles worm, pleocidin, Avermectin, Avrmectin, Affirm (Merck Co.), 5a,6,9,9a-hexahydro-6,9-methano-2,4, ethiprole, ethiprole, flufenoxuron, desinsection is grand, difenolan, pyriproxyfen, pymetrozine, amitraz, Su Yun gold bar mattress, Bacillus thuringiensis δ endotoxin or predacious fungi.
Described composition is preferably made the unrestrained profit of soil liquid preparation.
The present invention also provides a kind of method of preventing and treating invertebrate pests, is with the composition contact invertebrate pests or its environment that contain with following formula I compound
The described composition that contains formula I compound, preferably contains the upper applicable salt of the compound shown in formula I or its agricultural, and is selected from one or more other components in tensio-active agent, solid diluent or liquid diluent.
Described composition more preferably further contains at least one other biological active compound or preparation.
Accompanying drawing explanation
Fig. 1 is the nuclear magnetic spectrogram of the compounds of this invention 1.
Fig. 2 is the GC-MS spectrogram of the compounds of this invention 1 and Rynaxypyr, and wherein Fig. 2 A is the GC-MS spectrogram of the compounds of this invention 1, and Fig. 2 B is the GC-MS spectrogram of Rynaxypyr.
Embodiment
By the form of embodiment, explain in detail technical scheme of the present invention and effect below, but the present invention is not limited to following examples.
Preparation Example 1
The deuterated methylamino-of the bromo-N-[4-chloro-2-methyl-6-[(tri-of 3-) carbonyl] phenyl] synthetic (formula V compound is denoted as the compounds of this invention 1) of-1-(3-chloro-2-pyridyl)-1H-pyrazoles-5-methane amide
Steps A. synthesizing of three deuterated methylamines
500 gram of three deuterated methanol and ammonia are by the fixation reaction bed of molecular sieve or aluminum oxide is housed at 350 ℃, and reactant condensation, obtains the mixture of three deuterated Monomethylamines, three deuterated dimethylamine, three deuterated Trimethylamine 99s, and rectifying obtains 99% three deuterated Monomethylamines.
Step is synthesizing of the deuterated amino-carbonyl aniline of methyl-6-tri-B.2-
In 250mL three-necked bottle, add 10.0g 2-amino-3-methyl-toluate, the three deuterated Monomethylamines that 80mL ethanol and 5g steps A obtain, under 50-60 ℃ of condition, react 12h, be chilled to room temperature, solvent is steamed in decompression, use methylene dichloride recrystallization, obtain the pale solid of the deuterated amino-carbonyl aniline of 11.3g2-methyl-6-tri-, yield 91%.
Step is synthesizing of the deuterated amino-carbonyl aniline of the chloro-6-tri-of methyl-4-C.2-
The deuterated amino-carbonyl aniline of 2-methyl-6-tri-, 60mLDMF and the 15g SULPHURYL CHLORIDE that in 250mL three-necked bottle, add 18.0g to obtain by step B method, in 20-30 ℃ of reaction 6h, be chilled to room temperature, reaction solution is poured onto in 180mL frozen water, filter, dry, re-crystallizing in ethyl acetate, obtain 19g pale solid, yield 90%.
Step is synthesizing of diazanyl-3-chloropyridine D.2-
In 500mL three-necked bottle, add successively 273mL 50% hydrazine hydrate, 100g (143mmo1) 2,3-dichloropyridine and 150mL ethanol, magnetic agitation reflux 30h, is cooled to room temperature, filters, is dried to obtain white solid 96g, yield 99%.
Synthesizing of step e .2-(3-chloropyridine-2-yl)-5-hydroxypyrazoles-3-ethyl formate
Be furnished with in churned mechanically 1L three-necked bottle and add 250mL ethanol, slowly add 15.5g (0.676mo1) sodium Metal 99.5, heating reflux reaction is made alcohol sodium solution.Under reflux state, add 96g (0.676mo1) 3-chloride-2-hydrazinopyridine, drip subsequently 116.3g (0.676mo1) ethyl maleate, continue backflow 5h, after cooling, ethanol is removed in underpressure distillation, adds 200mL water, under fully stirring, adds 40.5g (0.676mo1) Glacial acetic acid in ice-water bath, ethyl acetate for water (300mL * 3) is extracted, merge organic phase, washing, anhydrous sodium sulfate drying, filter also concentrating under reduced pressure and obtain 72.8g yellow solid, yield 40%.
The bromo-1-of step F .3-(3-chloropyridine-2-yl)-4,5-dihydro-1 h-pyrazole-5-ethyl formate synthetic
In 500mL reaction flask, add the compound, 100mL acetonitrile and 15.0g (52.3mmo1) the tribromo oxygen phosphorus that in 33.0g (122mmo1) E step, obtain, reflux 2h, acetonitrile is removed in underpressure distillation, add 100mL acetic acid ethyl dissolution, be washed to neutrality, anhydrous sodium sulfate drying, filters and concentrating under reduced pressure obtains 40.0g brown oil, yield 99%.HNMR(CDC 1
3，300MHz)，δ：1.19(t，3H，CH
3)，3.23(dd，1H，CH
2)，3.44(dd，1H，CH
2)，4.17(q，2H，CH
2CH
3)，5.25(dd，1H，CH)，6.86(dd，1H，Pyridin-5-H)，7.66(d，1H，Pyridin-4-H)，8.07(d，1H，Pyridin-6-H)。
Step is synthesizing of bromo-1-(3-chloro-2-pyridyl)-1H-pyrazole-5-ethyl formate G.3-
In 500mL reaction flask, add the compound obtaining in 6.0g (18mmo1) F step, 80mL acetonitrile, 3.6g (36mmo1) vitriol oil and 7.3g (36mmo1) Potassium Persulphate, heating reflux reaction 6h, cooling, acetonitrile is removed in underpressure distillation, add 50mL water, under room temperature, stir, filter to obtain orange/yellow solid 6.0g, yield 99%.
1H NMR(CDCl
3，300MHz)，δ：1.21(t，3H，CH
3)，4.22(q，2H，CH
2)，7.03(s，1H，Pyrazole)，7.45(dd，1H，Pyridin-5-H)，7.91(d，Pyridin-4-H)，8.50(d，1H，Pyridin-6-H)。
Step is synthesizing of bromo-1-(3-chloro-2-pyridyl)-1H-pyrazoles-5-formic acid H.3-
In 500mL reaction flask, add the bromo-1-of 35.1g (106mmo1) 3-(3-chloro-2-pyridyl)-1H-pyrazole-5-ethyl formate, 8.49g (212mmo1) sodium hydroxide and 200mL water, heating reflux reaction 3.5h, naturally cool to room temperature, under ice-water bath, with concentrated hydrochloric acid, be adjusted to pH=5, separate out solid, stirring at room 30 minutes, filter, be dried to obtain yellow solid 29.5g, yield 93%.
1HNMR(CDCl
3，300MHz)，δ：7.08(s，1H，Pyrazole)，7.43(dd，1H，Pyridin-5-H)，7.90(dd，1H，Pyridin-4-H)，8.50(dd，1H，Pyridin-6-H)。
Step is the deuterated methylamino-of bromo-N-[4-chloro-2-methyl-6-[(tri-I.3-) carbonyl] phenyl]-1-(3-chloro-2-pyridyl)-1H-pyrazoles-5-methane amide (compound 1) synthetic
The bromo-1-of 3-(3-chloro-2-pyridyl)-1H-pyrazoles-5-formic acid, 10 grams of phosphorus oxychloride prepared by the deuterated amino-carbonyl aniline of the chloro-6-tri-of 2-methyl-3-, 60mL acetonitrile, the 7.3g step H method that adds 5.5g to prepare by step C method in 100mL three-necked bottle, stirring at room 0.5h.Add 100mL aqueous methylamine solution, room temperature reaction 2h, acetonitrile is removed in underpressure distillation, and decrease temperature crystalline adds 40mL ethyl acetate, washing, anhydrous sodium sulfate drying, filters and concentrating under reduced pressure obtains white solid 10.74g, yield 88%.H NMR(CDC1
3，600MHz)，δ：2.17(S，3H，ArCH
3)，6.15(d，1H，NH)，7.11(s，1H，Pyrazole)，7.23(s，1H，ArH)，7.26(s，1H，ArH)，7.37(dd，1H，Pyridin-5-H)，7.84(dd，Pyri-din-4-H)，8.45(dd，1H，Pyridin-6-H)，10.07(s，1H，ArNH)。Nuclear magnetic spectrogram is shown in accompanying drawing 1.
GC-MS spectrogram shows that the M+1 peak molecular weight of compound 1 is 485, more 3 than corresponding full H compound Rynaxypyr, is really the product that 3 D replace.Relatively mass spectrum is shown in accompanying drawing 2.
Preparation Example 2
The deuterated methylamino-of the bromo-N-[4-chloro-2-methyl-6-[(mono-of 3-) carbonyl] phenyl]-1-(3-chloro-2-pyridyl)-1H-pyrazoles-5-methane amide (compound of formula of the present invention (VII) is denoted as compound 2) synthetic
Steps A. synthesizing of a deuterated methylamine
500 gram of one deuterated methanol and ammonia are by the fixation reaction bed of molecular sieve or aluminum oxide is housed at 350 ℃, and reactant condensation, obtains the mixture of a deuterated Monomethylamine, a deuterated dimethylamine, a deuterated Trimethylamine 99, and rectifying obtains a deuterated Monomethylamine of 99%.
Step is the deuterated methylamino-of bromo-N-[4-chloro-2-methyl-6-[(mono-B.3-) carbonyl] phenyl]-1-(3-chloro-2-pyridyl)-1H-pyrazoles-5-methane amide (compound 2) synthetic
With reference to Preparation Example 1, a deuterated Monomethylamine prepared by the present embodiment steps A method of take is starting raw material, the deuterated amino-carbonyl aniline of the preparation chloro-6-mono-of 2-methyl-3-, react and obtain the deuterated methylamino-of the bromo-N-[4-chloro-2-methyl-6-[(mono-of compound 2:3-with the bromo-1-of 3-(3-chloro-2-pyridyl)-1H-pyrazoles-5-formic acid) carbonyl] phenyl]-1-(3-chloro-2-pyridyl)-1H-pyrazoles-5-methane amide, HNMR (CDC1
3, 300MHz), δ: 2.28 (S, 3H, ArCH
3), 2.96 (d, 2H, NHCDH
2), 6.17 (d, 1H, NH), 7.13 (s, 1H, Pyrazole), 7.21 (s, 1H, ArH), 7.24 (s, 1H, ArH), 7.38 (dd, 1H, Pyridin-5-H), 7.85 (dd, 1H, Pyri-din-4-H), 8.56 (dd, 1H, Pyridin-6-H), 10.28 (s, 1H, ArNH).
Preparation Example 3
The bromo-N-[4-cyano group-2-of 3-methyl-6-[(tri-deuterated methylamino-s) carbonyl] phenyl]-1-(3-chloro-2-pyridyl)-1H-pyrazoles-5-methane amide (compound of formula of the present invention (VIII) is denoted as compound 3) synthetic
With reference to Preparation Example 1, with 2-methyl-4-cyano group-6-tri-deuterated amino-carbonyl aniline, react and obtain the bromo-N-[4-cyano group-2-of compound 3 faint yellow solids: 3-methyl-6-[(tri-deuterated methylamino-s with the bromo-1-of 3-(3-chloro-2-pyridyl)-1H-pyrazoles-5-formic acid) carbonyl] phenyl]-1-(3-chloro-2-pyridyl)-1H-pyrazoles-5-methane amide, H NMR (CDC1
3, 300MHz), δ: 2.18 (S, 3H, ArCH
3), 6.30 (d, 1H, NH), 7.12 (s, 1H, Pyrazole), 7.21 (s, 1H, ArH), 7.24 (s, 1H, ArH), 7.38 (dd, 1H, Pyridin-5-H), 7.83 (dd, 1H, Pyri-din-4-H), 8.45 (dd, 1H, Pyridin-6-H), 10.03 (s, 1H, ArNH).
Preparation Example 4
The bromo-N-[4-cyano group-2-of 3-methyl-6-[(bis-deuterated methylamino-s) carbonyl] phenyl]-1-(3-chloro-2-pyridyl)-1H-pyrazoles-5-methane amide (compound of formula of the present invention (IX) is denoted as compound 4) synthetic
Steps A. synthesizing of two deuterated methylamines
500 gram of two deuterated methanol and ammonia are by the fixation reaction bed of molecular sieve or aluminum oxide is housed at 350 ℃, and reactant condensation, obtains the mixture of two deuterated Monomethylamines, two deuterated dimethylamine, two deuterated Trimethylamine 99s, and rectifying obtains 99% two deuterated Monomethylamines.
Step B. intermediate 6-cyano group-2-(the bromo-1-of 3-(3-chloropyridine-2-yl)-1H-pyrazoles-5-yl)-8-methyl-4H-3,1-benzoxazine-4 synthetic
By the bromo-1-of 3-(3-chloropyridine-2-yl)-1H-pyrazoles-5-formic acid (31.6g, 0.1mo1) and 2-amino-5-cyano-3-tolyl acid (17.6g, 0.1mol) add in the 1000mL reaction flask that 500mL acetonitrile is housed, stir the lower 40mL of dropping pyridine, reaction raw materials all dissolves, ice bath is down to 0 ℃, slowly drip 20mL Methanesulfonyl chloride, dropwise 10min recession deicing and bathe, room temperature is stirred 3h, has consubstantiality to separate out, partial solvent is sloughed in decompression, filter to obtain faint yellow solid 38.1g, thick yield 86%, does not further process and is directly used in the next step.
Step C: compound 4 synthetic
Step B product is packed in the 500mL reaction flask of 200mL acetonitrile, 25% aqueous solution that adds the two deuterated Monomethylamines that 10mL steps A obtains), under room temperature, react 1h, the faint yellow solid compound 4 of purifying to obtain---the bromo-N-[4-cyano group-2-of 3-methyl-6-[(bis-deuterated methylamino-s) carbonyl] phenyl]-1-(3-chloro-2-pyridyl)-1H-pyrazoles-5-methane amide 24.2g.H NMR(CDC1
3，300MHz)，δ：2.18(S，3H，ArCH
3)，2.80(d，1H，NHCD
2H)6.30(d，1H，NH)，7.12(s，1H，Pyrazole)，7.21(s，1H，ArH)，7.24(s，1H，ArH)，7.38(dd，1H，Pyridin-5-H)，7.83(dd，1H，Pyri-din-4-H)，8.45(dd，1H，Pyridin-6-H)，10.03(s，1H，ArNH)。
FORMULATION EXAMPLE 1
Drop into respectively the compounds of this invention 1,2,3,4 each 20g of aforementioned Preparation Example, and supporting other auxiliary materials 4g naphthalenesulfonate, 3g alkylsulfonate, 5g propylene glycol, 0.2g xanthan gum, 0.15g potassium sorbate, water are mended to 100g, after mixing, adopt sand mill to grind 2 hours, make 20% compound suspension agent.
FORMULATION EXAMPLE 2
Use respectively the compounds of this invention 1,2,3,4 each 6g of aforementioned Preparation Example, and supporting other auxiliary materials 3g alkylbenzene polyoxyethylene ether phosphate, 4g sulfonated lignin, kaolin mend to 100g, mix by micronizer mill pulverize make 6% the compounds of this invention can wet-milling.
FORMULATION EXAMPLE 3
Respectively by the compounds of this invention of aforementioned Preparation Example 1,2,3,4 each 5g, add 3g lambda-cyhalothrin, and supporting other auxiliary materials 3g alkylbenzene polyoxyethylene ether phosphate, 4g sulfonated lignin, kaolin mend to 100g, mix by micronizer mill pulverize make 8% can wet-milling.
FORMULATION EXAMPLE 4
Respectively by the compounds of this invention of aforementioned Preparation Example 1,2,3,4 each 10g, add respectively 15g pymetrozine, and supporting other auxiliary materials 2g alkylbenzene polyoxyethylene ether phosphate, 6g sulfonated lignin, 10g W-Gum, 5g ammonium sulfate, 2g Walocel MT 20.000PV, diatomite are mended to 100g.Mixing, after micronizer mill is pulverized, adds water and mixes through Squeezinggranulator granulation, dries and be granulation into 25% water dispersible granules.
FORMULATION EXAMPLE 5
By 15g compound 1 and 10g Provado, and supporting other auxiliary materials 2g alkylbenzene polyoxyethylene ether phosphate, 6g sulfonated lignin, 10g W-Gum, 5g ammonium sulfate, 2g Walocel MT 20.000PV, diatomite are mended to 100g.Mixing, after micronizer mill is pulverized, adds water and mixes through Squeezinggranulator granulation, dries and be granulation into 25% water dispersible granules.
FORMULATION EXAMPLE 6
By 12.5g compound 2 and 12.5g Diacloden, and supporting other auxiliary materials 2g alkylbenzene polyoxyethylene ether phosphate, 6g sulfonated lignin, 10g W-Gum, 5g ammonium sulfate, 2g Walocel MT 20.000PV, diatomite are mended to 100g.Mixing, after micronizer mill is pulverized, adds water and mixes through Squeezinggranulator granulation, dries and be granulation into 25% water dispersible granules.
FORMULATION EXAMPLE 7
By 10g compound 3 and 15g clothianidin, and supporting other auxiliary materials 2g alkylbenzene polyoxyethylene ether phosphate, 6g sulfonated lignin, 10g W-Gum, 5g ammonium sulfate, 2g Walocel MT 20.000PV, diatomite are mended to 100g.Mixing, after micronizer mill is pulverized, adds water and mixes through Squeezinggranulator granulation, dries and be granulation into 25% water dispersible granules.
Test implementation example 1
Adopt pickling process to measure.Respectively using compound 1 and 2 and control compound Rynaxypyr as former medicine, be dissolved in advance acetone, and adopt the distilled water containing 0.5 ‰ tween-80s to dilute, by geometric progression, be diluted to and be diluted to respectively 0.125 μ g/ml, 0.25 μ g/ml, 0.5 μ g/ml, 1.0 μ g/ml, 2.0 μ g/ml, 4.0 μ g/ml, 6 concentration.3 repetitions are established in every processing, each repeat with 20 4 mid-term in age Chilo spp larvae, larva is concentrated on to steeping cell.Soak 5s in liquid after, be transferred in the culture dish that fresh Culm of Rice is housed, and set up the distillation water logging that adopts 0.5 ‰ tween-80s from as CK.Dipping finishes that to put into temperature be 25 ℃, in the constant incubator that periodicity of illumination is L:D:16h:8h, cultivates, and checks dead borer population after 48h.Death standard is that polypide is felt like jelly, stand up in rear 30s and can not overturn, or with acupuncture polypide surface without voluntary response, health blackout.Finally according to mortality ratio, calculate virulence regression equation and LC50, the results are shown in Table 1 and table 2.
Table 1.48 hour striped rice borer mortality statistics
Table 2. virulence regression equation calculates
| Sample | Virulence regression equation | LC50μg/ml |
| Compound 1 | Y=6.2141＋2.5599X | 0.3355 |
| Compound 2 | Y=6.1315＋2.5361X | 0.3580 |
| Rynaxypyr | Y=5.9916＋2.5507X | 0.4085 |
From test result, the compounds of this invention 1 and compound 2 remove and kill in activity indoor test striped rice borer, better than Rynaxypyr.
The raw test of test implementation example 2. control brassicaceous vegetable (wild cabbage) insect is tested
Target: lepidoptera pest small cabbage moth
Method: adopt pickling process to measure.Respectively using compound 3 and 4 and control compound bromine cyanogen insect amide (cyantranilipro1e) as former medicine, be dissolved in advance acetone, and adopt the distilled water containing 0.5 ‰ tween-80s to dilute, by geometric progression, be diluted to and be diluted to respectively 0.125 μ g/ml, 0.25 μ g/ml, 0.5 μ g/ml, 1.0 μ g/ml, 2.0 μ g/ml, 4.0 μ g/ml, 6 concentration.Employing leaf dipping method is measured, by diameter 2cm cabbage leaves soak take out after into the liquid 10 seconds air-dry, in each culture dish, place 3,10 of every ware picking diamondback moth larvaes in three ages, then put into 25 ℃ of illumination boxs, after 48 hours, investigate respectively survival borer population, calculate mortality ratio, pass through the mortality ratio data of 6 concentration gradients, calculate virulence regression equation, finally obtain LC50.Measurement result following (table 3 and 4)
Table 3.48 hour small cabbage moth mortality statistics
Table 4. virulence regression equation calculates
| Sample | Virulence regression equation | LC50μg/ml |
| Compound 3 | Y=6.8463＋2.8068X | 0.2167 |
| Compound 4 | Y=6.7940＋2.8517X | 0.2349 |
| Bromine cyanogen insect amide | Y=6.4659＋2.4880X | 0.2561 |
From test result, the compounds of this invention 3 and compound 4 remove and kill in activity indoor test small cabbage moth, better than the non-deuterated compound bromine cyanogen insect amide of correspondence.
Claims (7)
1. the compound shown in a formula I
Wherein, R
1cH
3, F, Cl or Br; R
2f, Cl, Br, I ,-CN or CF
3; R
3cF
3, Cl, Br or OCH
2cF
3; R
4cl or Br; X gets 0～2 integer, and X+Y=3.
2. compound claimed in claim 1, is characterized in that: in described formula (I), x is that 0, y is 3, and compound structure is suc as formula shown in (II)
Or
In described formula (I), x is that 2, y is 1, and compound structure is as shown in formula IV
3. compound claimed in claim 1, is characterized in that, described compound structure as below:
4. the preparation method of compound described in claim 1, comprises the following steps:
1) deuterated methanol is through the synthetic deuterated methylamine of ammonification, and deuterated methylamine and substituted aroma phenylformic acid obtain substituted aroma benzamide through amination; Reaction process is as follows, wherein R
1cH
3, F, Cl or Br; X gets 0～2 integer, and X+Y=3;
2) substituted aroma benzamide is through the synthetic Halogen substituted aroma benzamide of halogenation; Reaction process is as follows, wherein R
1define same step 1); R
2f, Cl, Br or I; X gets 0～2 integer, and X+Y=3;
3) the synthetic hydrazino pyridine that replaces of substituted pyridines and hydrazine, then generates substituted pyridinyl pyrazoline with maleic acid ester cyclization; Reaction process is as follows, wherein R
4cl or Br;
4) hydroxyl of substituted pyridinyl pyrazoline is halogenated synthesizing halogen pyridyl pyrazoline, halogenated pyridyl pyrazoline dehydrogenation synthesizing halogen pyridyl pyrazoles; Reaction process is as follows, wherein R
3cl, Br; R
4define same step 3);
5) the Halogen substituted aroma benzamide and the step 4 that step 2) obtain) the deuterated Anthranilamide compound of object product shown in the pyrazole-fused production of halogenated pyridyl (I) that obtains; Reaction process is as follows, wherein R
1, R
2, R
3, R
4, X and Y definition the same
5. the application of formula I compound in the composition that contains formula I compound of preparation control invertebrate pests,
Wherein, R
1cH
3, F, Cl or Br; R
2f, Cl, Br, I ,-CN or CF
3; R
3cF
3, Cl, Br or OCH
2cF
3; R
4cl or Br; X gets 0～2 integer, and X+Y=3.
6. application claimed in claim 5, it is characterized in that: the described composition that contains formula I compound, contain the upper applicable salt of the compound shown in formula I or its agricultural, and be selected from one or more other components in tensio-active agent, solid diluent or liquid diluent.
7. application claimed in claim 5, is characterized in that: described composition also further contains at least one other biological active compound or preparation.
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| CN104459001B (en) * | 2014-12-30 | 2016-01-20 | 郭庆龙 | The assay method of Rynaxypyr residual quantity in a kind of fruits and vegetables |
| CN104502507B (en) * | 2014-12-30 | 2016-05-18 | 郭庆龙 | A kind of GC-NCI-MS assay method of Rynaxypyr residual quantity |
| CN104502504B (en) * | 2014-12-30 | 2016-03-30 | 郭庆龙 | The assay method of Rynaxypyr residual quantity in a kind of vegetables and fruit |
| CN107033135B (en) * | 2017-05-26 | 2020-09-11 | 浙江省诸暨合力化学对外贸易有限公司 | Method for preparing isooxazinone compound and application thereof |
| CN110396079A (en) * | 2019-06-12 | 2019-11-01 | 东南大学 | A kind of preparation method and applications of Rynaxypyr intermediate |
| CN112321563A (en) * | 2020-10-04 | 2021-02-05 | 浙江埃森化学有限公司 | Preparation method of chlorantraniliprole key intermediate K acid |
| CN115557931A (en) * | 2022-10-20 | 2023-01-03 | 浙江新安化工集团股份有限公司 | Efficient synthesis method of 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formic acid |
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| CN102627629A (en) * | 2012-04-16 | 2012-08-08 | 江苏扬农化工股份有限公司 | Novel deutero anthranilamide compound and application thereof |
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| CN102113516A (en) * | 2010-01-05 | 2011-07-06 | 海南正业中农高科股份有限公司 | Insect killing compound containing chlorantraniliprole |
| CN102627629A (en) * | 2012-04-16 | 2012-08-08 | 江苏扬农化工股份有限公司 | Novel deutero anthranilamide compound and application thereof |
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