CN1051731A - Herbicidal compound, its preparation method and methods for using them - Google Patents

Abstract

Make weedicide with compounds shown in the following structural formula: R wherein ₁But be substituted pyrazole base, R ₂And R ₃Be respectively low alkyl group or lower alkoxy; With Z be CH or N.

Description

Herbicidal compound, its preparation method and methods for using them

The present invention is in relation to novel herbicides compounds, more particularly, it relates to compound as follows:

R in formula¹For can substituted pyrazolyl;R₂And R₃Respectively perhaps lower alkoxy and Z are CH or N to low alkyl group.

Compound (1) not only all shows excellent activity of weeding to weeds in paddy field and upland weeds, but also right, such as rice, wheat, barley, corn or Soybean and Other Crops do not generate phytotoxicity, to serve as excellent selective herbicide.

Up to the present, have various chemical medicaments and be used as herbicide.But just to the high herbicidals of weeds activity, to the low phytotoxicity of crop, to mammal, the hypotoxicity of fish and shellfish, and prevent for the requirements such as pollution to environment, these herbicides can't be satisfactory.

For example, in pyrazole compound, it is known that the compound (see Japanese No. 78980/1985 Unexamined Publication patent application) of following structural has activity of weeding:

A is hydrogen or low alkyl group etc. in formula;B is hydrogen or low alkyl group;D is that wherein Q is low alkyl group etc. to-COOQ();K, G is respectively low alkyl group or lower alkoxy etc.;And E is nitrogen etc..

From this part of patent it is contemplated that by the structural compounds

Base is converted into

The noval chemical compound obtained after base, activity of weeding will not be lower than the activity of weeding of compound shown in the structural formula.

But the present inventor is not it has been proved that the compound obtained in this way shows excellent activity of weeding.

The present inventor those described above compound is conducted in-depth research and it was unexpectedly found that, further described is hadThe compound of base, which carries out compounds obtained from ring-closure reaction, has quite high activity of weeding.

The present inventor has made further research again according to these discoveries, so as to complete the present invention.

Reference structure formula (I), by R₁Shown in pyrazolyl include pyrazole-3-yl, pyrazoles -4- base and pyrazoles -5- base, and most preferably pyrazoles -5- group.The substituent group that these pyrazolyls can be suitable for is upper at an arbitrary position to be replaced, and substituent group number is 1 to 3.

On these pyrazolyls the specific example of substituent group include low alkyl group, low-grade alkenyl, low-grade alkynyl, lower alkoxy, rudimentary alkenyloxy group, aryl, aryloxy group, aralkyl, aralkoxy, acyl group, acyloxy, carbamoyl, carbamoyloxy, sulfamoyl, halogen, can be with esterified carboxyl, nitro, cyano and following groups:

R in formula₄For organic residue, n is integer 0,1 or 2.In above-mentioned definition, low alkyl group is preferably the straight chain with 1 to 6 carbon atom, branch perhaps naphthenic base such as methyl, ethyl, n-propyl, isopropyl, normal-butyl, isobutyl group, sec-butyl, tert-butyl, n-pentyl, sec-amyl, isopentyl, neopentyl, n-hexyl, isohesyl, cyclopropyl, cyclobutyl, cyclopenta or cyclohexyl.Low-grade alkenyl is preferably the straight chain with 3 to 6 carbon atoms, branch perhaps cycloalkenyl such as allyl, isopropenyl, 1- cyclobutenyl, 2- pentenyl, 2- hexenyl, cyclopropanyl, cyclobutane base or cyclohexenyl group.Low-grade alkynyl is preferably to have the straight chain of 3 to 6 carbon atoms perhaps branch alkynyl such as propargyl, 2- butynyl, 3- butynyl, 3- pentynyl or 3- hexin base.Lower alkoxy, it is preferable to have the straight chain of 1 to 6 carbon atom perhaps branched alkoxy such as methoxyl group, ethyoxyl, positive propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, n-pentyloxy or positive hexyloxy.Alkenyloxy group is preferably the straight chain, branch or cyclenes oxygroup with 3 to 6 carbon atoms, such as allyloxy, 2- amylene oxygroup, hexamethylene alkenyloxy group.Aryl is preferably the aryl with 6 to 12 carbon atoms, such as phenyl, naphthalene or xenyl.Aryloxy group is preferably the aryloxy group with 6 to 12 carbon atoms, such as phenoxy group or naphthoxy.Aralkyl is preferably the aralkyl with 7 to 10 carbon atoms, such as benzyl, phenethyl or phenylpropyl.Aralkoxy is preferably the aralkoxy with 7 to 10 carbon atoms, such as benzyloxy, benzene ethyoxyl, phenylpropyl alcohol oxygroup.Acyl group is preferably the acyl group being derived from organic carboxyl acid, such as lower alkylcarbonyl, low-grade alkenyl carbonyl, aryl carbonyl, aromatic alkyl carbonyl is (in these definition, low alkyl group in lower alkylcarbonyl, low-grade alkenyl in low-grade alkenyl carbonyl, the definition of the aralkyl in aryl and aromatic alkyl carbonyl in aryl carbonyl is as defined above) or heterocyclecarbonyl (heterocycle therein preferably has at least one sulphur atom, 5 yuan or 6 circle heterocyclic ring bases of one oxygen atom or a nitrogen-atoms, such as thienyl, benzo thienyl, pyrrole radicals, oxazolyl, piperazinyl, thiazolyl, thiadiazolyl group, pyrazolyl, tetrazole radical or oxathiin base (oxathilnyl), and more specifically, it is acetyl group, propiono, bytyry, valeryl, caproyl, benzoyl, naphthalene Formoxyl, benzene first carbonyl, phenylethylcarbonyl, thienyl carbonyl or benzo thienyl carbonyl.Acyloxy is expressed from the next:

(A is acyl group as defined above in formula), such as acetoxyl group, propionyloxy, butyryl acyloxy, valeryl oxygroup, hexylyloxy, methylbenzylcarbonyl oxygroup, phenylethylcarbonyl oxygroup, benzoyloxy, Naphthoyloxy, thiophene grace base carbonyl oxygroup or benzo thienyl carbonyl oxygroup.Halogen is fluorine, chlorine, bromine or iodine.R₄Representative organic residue includes low alkyl group, low-grade alkenyl, lower alkoxy, rudimentary alkenyloxy group, aryl, aryloxy group, aralkyl, aralkoxy and heterocycle as described above.

Above-mentioned low alkyl group, low-grade alkenyl, low-grade alkynyl and lower alkoxy can carry out one to three by following radicals and replace: lower alkylthio, such as straight chain with 1 to 4 carbon atom or the alkylthio group such as methyl mercapto, ethylmercapto group, positive rosickyite base or the isobutylthio that have branch, halogen such as fluorine, chlorine, bromine or iodine, alkoxy, such as the straight chain with 1 to 6 carbon atom perhaps has alkoxy such as methoxyl group, ethyoxyl, positive propoxy, tert-butoxy or positive hexyloxy or/and the nitro of branch.

Above-mentioned aryl, aralkyl, aralkoxy and aryloxy group can carry out one to three by following radicals and replace: low alkyl group, low-grade alkenyl, low-grade alkynyl, lower alkoxy, acyl group, acyloxy, nitro, cyano, halogen, acyl group amido or/and lower alkylthio.In these definition, the definition of low alkyl group, low-grade alkenyl, low-grade alkynyl, lower alkoxy, acyl group, acyloxy, halogen and lower alkylthio is same as above.Acyl amino is that a substitution or disubstituted amino are carried out by acyl group as described above.

Above-mentioned carbamoyl, carbamoyloxy and sulfamoyl can be carried out one by low alkyl group, lower alkoxy, aryl or/and aralkyl and replace or two replace.In these definition, low alkyl group, lower alkoxy, the definition of aryl and aralkyl are same as above.

It is above-mentioned can esterified carboxyl be the carboxyl that can be esterified by following radicals: low alkyl group, low-grade alkenyl, low-grade alkynyl, aryl, aralkyl, acyl group or heterocycle as escribed above.

In compound defined above, compound preferably as follows:

R in formula₁' for one can be carried out to trisubstituted pyrazolyl by following radicals: low alkyl group, low-grade alkynyl, lower alkoxy, aryl, aralkyl, aralkoxy, one can be carried out by low alkyl group replaces or disubstituted carbamoyl, halogen, the carboxyl that can be esterified as needed, nitro, cyano or/and group as follows at low-grade alkenyl:

R in formula₄For low alkyl group;And n is 0,1 or 2;And the definition of other code names with it is as described above identical.

In R₁' definition in; low alkyl group and the low alkyl group that can be carried out by rudimentary group in a substitution or disubstituted carbamoyl are preferably the straight chain with 1 to 6 carbon atom; there are perhaps naphthenic base such as methyl, ethyl, n-propyl, isopropyl, normal-butyl, isobutyl group, sec-butyl, tert-butyl, n-pentyl, sec-amyl, isopentyl, neopentyl, n-hexyl, isohesyl, cyclopropyl, cyclobutyl, cyclopenta or the cyclohexyl of branch;Low-grade alkenyl is preferably alkenyl such as allyl, isopropenyl, 1- cyclobutenyl, 2- pentenyl or the 2- hexenyl that there is the straight chain of 3 to 6 carbon atoms perhaps to have branch;Low-grade alkynyl is preferably alkynyl such as propargyl, 2- butynyl, 3- butynyl, 3- pentynyl or the 3- hexin base that there is the straight chain of 3 to 6 carbon atoms perhaps to have branch;Lower alkoxy is preferably alkoxy such as methoxyl group, ethyoxyl, positive propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, n-pentyloxy or the positive hexyloxy that there is the straight chain of 1 to 6 carbon atom perhaps to have branch;Aryl is preferably the aryl with 6 to 12 carbon atoms, such as phenyl, naphthalene or xenyl;Aralkyl is preferably the aralkyl with 7 to 10 carbon atoms, such as benzyl, phenethyl or phenylpropyl;Aralkoxy is preferably the aralkoxy with 7 to 10 carbon atoms, such as benzyloxy, benzene ethyoxyl or phenylpropyl alcohol oxygroup;Halogen is fluorine, chlorine, bromine or iodine;And the carboxyl being esterified as needed is the carboxyl that can be esterified by above-mentioned low alkyl group, low-grade alkenyl, low-grade alkynyl, aryl or aralkyl.

One is carried out by rudimentary group to replace or the specific example of disubstituted carbamoyl includes N- methylcarbamoyl, N- ethylaminocarbonyl, N, N- formyl-dimethylamino, N, N- diethylamino formoxyl and N- methyl-N-propylamino formoxyl.

The specific example of the carboxyl of esterification includes methoxycarbonyl, ethoxy carbonyl, positive propoxy carbonyl, isopropoxy carbonyl, n-butoxycarbonyl, isobutoxy carbonyl, tert-butoxycarbonyl, phenyloxycarbonyl, naphthoxycarbonyl, Benzyloxycarbonyl, benzhydryloxycarbonyl and trityloxycarbonyl.

R₄The definition of representative low alkyl group and R₁' in definition it is identical.

Group representated by following structural:

Specific example include methyl mercapto, ethylmercapto group, positive rosickyite base, tertiary butylthio, methylsulfinyl, ethylsulfinyl, isopropylsulphinyl, methyl sulphonyl, ethylsulfonyl, n-propyl sulfonyl and n-hexyl sulfonyl.

It is further preferred that R₁For that can carry out one to trisubstituted pyrazoles -5- base by following radicals: low alkyl group can be carried out one by low alkyl group and replace or disubstituted carbamoyl, the carboxyl that is esterified as needed or/and halogen.Most preferably, R₁Pyrazoles -5- the base being as follows:

R in formula₅For low alkyl group;R₆For hydrogen or low alkyl group;And R₇For the carboxyl being esterified when necessary, halogen or one can be carried out by low alkyl group replace or disubstituted carbamoyl.

In these definition, R₅Or R₆Representative low alkyl group, the carboxyl being esterified as needed, by R₇Represent can by low alkyl group carry out one replace or disubstituted carbamoyl in low alkyl group and halogen definition and R₁In definition it is identical.

In group as defined above, it is desirable to, R₅For methyl;R₆For hydrogen or methyl;And R₇For carboxyl, formyl-dimethylamino or the halogen being esterified by alkyl with 1 to 4 carbon atoms (such as methyl, ethyl, n-propyl, isopropyl, normal-butyl or tert-butyl).It is more desirable to be, R₅For methyl, R₆For hydrogen or methyl, and R₇For methoxycarbonyl or ethoxy carbonyl.

By R₂And R₃Representative low alkyl group is the straight chain with 1 to 6 carbon atom, there are perhaps naphthenic base such as methyl, ethyl, n-propyl, isopropyl, normal-butyl, isobutyl group, sec-butyl, tert-butyl, n-pentyl, sec-amyl, isopentyl, neopentyl, n-hexyl, isohesyl, cyclopropyl, cyclobutyl, cyclopenta or the cyclohexyl of branch.By R₂And R₃Representative lower alkoxy is alkoxy such as methoxyl group, ethyoxyl, positive propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, n-pentyloxy or the positive hexyloxy of the perhaps branch of the straight chain with 1 to 6 carbon atom.

Preferably, R₂And R₃Respectively alkyl with 1 to 4 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, normal-butyl or tertiary fourth grade, perhaps alkoxy such as methoxyl group, ethyoxyl, positive propoxy, isopropoxy, n-butoxy or tert-butoxy with 1 to 4 carbon atom.Preferably, R₂And R₃Respectively methyl or methoxyl group.In these defined groups, it is desirable to, R₂For methyl or methoxyl group, and R₃For methoxyl group.

, can be with alkali when compound (I) contains acidic group, such as when carboxyl, such as sodium, potassium or aluminium are at salt.

Compound (I) not only shows the activity of weeding of excellent broad spectrum in the case where dosage is extremely low to various weeds, these weeds include weeds in paddy field, such as:

Echinochloa (Echinochloa oryzicola),

Difformed galingale herb (Cyperus difformis),

Firefly Lin (Scirpus juncoides),

Monochoria vaginalis (Monochoria vaginalis),

Short arrowhead (Sagittaria pygmaea),

Needle spikesedge herb (Eleocharis acicularis),

Herba Cyperi Glomerati (Cyperus serotinus),

Eleocharis (Eleocharis kuroguwai),

A.canaliculatum (Alisma canaliculatum),

Angustifolia arrowhead herb (Sagittaria trifolia),

(Scirpus wallichii),

Vandellia (Lindernia procumbens),

Mexicana (Rotala indica),

Potamogeton (Potamogeton distinctus),

False loosestrife (Ludwiga prastrata), or

(Flatine triandia),

And upland weeds, such as:

Knotgrass (Digltaria adscendens),

Thick purple herba setariae viridis (Setaria viridis),

Wild amaranth (Amaranthus viridis),

Piemarker (Abutilon theophrastl),

Chenopodiaceae (Chenopodium album),

Korean persicary (Polygonum longisetum),

Purslane (Portulaca oleracea),

It pierces chrysanthemum and twists (Sida splnosa),

Datura (Datura stamonium),

Garden leaf leads a cow (Ipomoea purpurea),

Siberian cocklebur (Xanthium strumarium),

Barnyard grass (Echinochloa crus-galli),

Panicum (Panicum dichotomiflorum),

Johnson grass (Sorghum halepense),

The rhizome of nutgrass flatsedge or nutgrass flatsedge (Cyperus rotundus),

Wild avena sativa (Arena fatua),

Rat-tail amur foxtail (Alopecurus myosuroides),

Cheatgrass brome (Bromus tectorum),

Herba stellariae mediae (Stellaria media),

Mustard category (Brassica Sp.),

Cassia (Cassia obtusifolia),

German chamomile (Matricaria chamomilla)

Or dayflower (Commelina communis),

And phytotoxicity will not be generated to crop, such as rice, wheat, barley, corn or soybean, thus be quite safe for these crops.

Compound (I) shows the herbicidal effect of high selectivity to various weeds as described above, for mammal, fish, shellfish, totally nontoxic, and it not will cause environmental pollution, the highly safe herbicide for rice field, nonirrigated farmland and bare place can thus be effectively served as.

When using compound (I) as herbicide, compound (I) can be using the use dosage form of agricultural chemicals known to any one, such as, can difference according to requirements and a kind of or no less than two kinds compounds (I) are dissolved in, or be suspended in suitable liquid-carrier (such as, solvent) among perhaps mix or be adsorbed on suitable carrier on suitable solid carrier, thus be made missible oil, oil solution, spray, wettable powder, pulvis, DL(is without drift) pulvis, granule, granula subtilis, F type granula subtilis and tablet.Also emulsifier, suspension aids, spreader-sticker, bleeding agent, wetting agent, thickener, stabilizer etc. can be added into these formulas if necessary.

The suitable specific example of the liquid-carrier used in herbicide (solvent) includes solvent, such as water, alcohols (such as methanol, ethyl alcohol, normal propyl alcohol, isopropanol or ethylene glycol), ketone (such as acetone or methyl ethyl ketone), ethers (such as dioxanes, tetrahydrofuran, ethylene glycol single methyl ether, diethylene glycol monomethyl ether or propylene glycol monomethyl ether), aliphatic hydrocarbon (such as kerosene, fuel oil or machine oil), aromatic hydrocarbons (such as benzene, toluene, dimethylbenzene, solvent naphtha or methyl naphthalene), halogenated hydrocarbon (such as methylene chloride, chloroform or carbon tetrachloride), amides (such as dimethylformamide or dimethyl acetamide), esters (such as ethyl acetate, the glyceride type of butyl acetate or fatty acid) either nitrile (such as acetonitrile or propionitrile).These liquid-carriers (solvent) can be used alone, the form of mixtures application that two kinds or more of can also be mixed to form in appropriate proportions.

The specific example of solid carrier (diluent, dust diluent), including Plant Powder (such as soy meal, tobacco powder, wheat flour perhaps sawdust), mineral powder (such as clay such as kaolin, bentonite or acid clay;Talcum, such as talcum powder or agalmatolite powder;Silica, such as diatomite or mica powder);Vanadine;Sulphur powder and active carbon.These solid carriers two kinds or more of can also can be mixed to form in appropriate proportions form of mixtures application with independent role.

The surfactant that can be used as described emulsifier, spreader-sticker, bleeding agent or dispersing agent includes non-ionic or anionic surfactant, such as soap;Polyethylene oxide base alkaryl ethers (such as the Noigen EA 142 that Dai Ichi Kogyo Seiyaku Co., Ltd. releases

〕;Polyethylene oxide base aryl esters (such as the Nornal that Dong Bang Chemical Co., Ltd., Japan releases

);Alkyl sulfate (such as the Emal 10 that Japanese crystal soda Co., Ltd releases

With Emal 40

);Alkyl sulfonates (such as the Neogen that Dai Ichi Kogyo Seiyaku Co., Ltd. releasesWith Neogen T

And the Neopelex that Japanese crystal soda Co., Ltd releases;Polyethylene glycol ethers (such as the Nonipol 85 that SANYO GS synthesis Co., Ltd releases

, Nonipol 100, Nonipol 160

);Or polyhydroxy alkyl ester (such as the Tween 20 that Japanese crystal soda Co., Ltd releases

With Tween 80

).

The concentration range of compound (I) in herbicide is that missible oil or wettable powder is such as made, and is about 10 to 90(weight) %;Oil solution, pulvis and DL(is such as made without drift) pulvis, then be about 0.1 to 10(weight) %, F type granula subtilis and granula subtilis is such as made, then is about 0.05 to 10%(weight).These concentration ranges can be adjusted depending on the application.For missible oil and wettable powder, can be administered again after place to use diluent, such as water dilution (such as 100 to 100000 times of dilution).

When compound (I) is used as herbicide, for rice field, the amount of application of herbicide is every acre about 0.05 to 50 grams, preferably 0.1 to 5 gram of active constituent (compound (I)), and for nonirrigated farmland, amount of application is 0.05 to 20 gram every acre, preferably 0.1 to 5 gram of active constituent (compound (I)), this certain amount ranges can according to application place, application season, the difference of method of administration, the type to be cut weeds etc. and be changed.

When being used to compound (I) to remove weeds in paddy field, preferably it is used as soil processing herbicide or base of leaf and soil processing herbicide before bud.

For example, herbicide provided by the invention can be safely administered, because even the herbicide also will never generate phytotoxicity to rice crop when applying immediately or in 2 to 3 weeks after transfer.

If necessary, herbicide of the invention can be mixed with other preparations, other preparations include other herbicides, plant growth regulator, fungicide (such as organochlorine class fungicide), organic sulfur class fungicide, pyroles fungicide or Antibiotics), insecticide (such as pyrethroid insecticide, organic phosphates insecticide or carbamates insecticide), acaricide, nematicide, synergist, attractant, repellents, colorant or/and fertilizer.

The available method of compound (I), such as at " heterocyclic chemistry magazine ", volume 20, prepared by method described in page 1127 (1983).Such as the compound that compound (I) can will be shown below carries out ring-closure reaction and is made:

Ring-closure reaction is carried out by dehydrogenation reaction under oxidative conditions.

This reaction contacts to carry out with oxidant generally by compound (II).The specific example of oxidant includes halogenating agent, such as halogen (such as chlorine, bromine or iodine), N- halosuccinimides class (such as N-chlorosuccinimide or N-bromosuccinimide), N- haloacetyl amine (such as N- chloro-acetamide or N- bromo acetamide), the halogenated phthalimide class of N- (such as N- chloro phthalimide or N- bromo phthalimide), toluene-sodium-sulfonchloramide, or hypohalogenous acids salt (such as sodium hypochlorite, postassium hypochlorite, calcium hypochlorite or sodium hypobromite);Sulfonyl halides, such as aryl sulfonyl halide class (such as benzene sulfonyl chloride perhaps paratoluensulfonyl chloride) heteroaryl-alkylsulfonyl halides class (such as mesyl chloride or ethyl sulfonic chloride or sulfonic acid chloride;Peroxide acids, such as hydrogen peroxide, peroxyformic acid, Peracetic acid, Perpropionic Acid, benzoyl hydroperoxide, monoperphthalic acid or trifluoro peracetic acid;(2) sulfate is crossed, such as crosses (two) sodium sulphate, mistake (two) potassium sulfate or crosses (two) ammonium sulfate;And the oxidant containing metal, such as selenium dioxide, manganese dioxide, silver oxide, brown lead oxide, mercury oxide, iron chloride, lead tetraacetate, the potassium ferricyanide, permanganate or high chromic acid content salt;Nitric acid, oxygen and air.

In this ring-closure reaction, the dosage of oxidant, which is subject to, must make fully reacting;Theoretically, every 1 mole of compound (II) just can produce active oxygen using 0.5 mole of oxidant.If oxidant used does not generate active oxygen at this time, then the dosage of oxidant rises to every 1 mole of compound (II) using 1 mole of oxidant to remove hydrogen.In general, it can cause to pay reaction using excessive oxidant, therefore to obtain the final products of high yield, not have to excessive oxidant preferably.

This reaction carries out in the solvent for not hindering the reaction.As solvent, can be used is inert solvent, such as water for the reaction;Alcohols, such as methanol, ethyl alcohol, normal propyl alcohol, isopropanol, n-butanol or the tert-butyl alcohol;Aromatic hydrocarbons, such as benzene,toluene,xylene, nitrobenzene or chlorobenzene;Halogenated hydrocarbon, such as methylene chloride, chloroform or carbon tetrachloride;Ethers, such as ether, dioxanes, isopropyl ether or tetrachloro furans (hereinafter referred to as THF);Ketone, such as acetone or methyl ethyl ketone;Nitrile, such as acetonitrile or propionitrile;Amides, such as dimethylformamide (hereinafter referred to as DMF), dimethyl acetamide (hereinafter referred to as DMAC) or hexamethylphosphoramide (HMPA);Esters, such as methyl acetate, ethyl acetate or butyl acetate;Sulfoxide type, such as dimethyl sulfoxide (hereinafter referred to as DMSO);Aliphatic carboxylic acid, such as formic acid, acetic acid or propionic acid;Or trimethylamine, such as pyridine, γ-collidine (i.e. 4- ethyl-alpha-methyl pyridine), quinoline, triethylamine, Tri-n-Propylamine or n,N-Dimethylaniline.These solvents can be used alone or are applied in the form of the two kinds or more of mixtures formed by arbitrary proportion.

This ring-closure reaction can carry out carrying out gently so as to react in the presence of alkali.The specific example of alkali used includes inorganic base, such as alkali metal hydroxide such as potassium hydroxide or sodium hydroxide, alkaline earth metal hydroxide such as calcium hydroxide, alkali metal hydrogencarbonate such as saleratus, alkaline earth metal carbonate (such as calcium carbonate) or ammonia;And organic base, such as trimethylamine, such as pyridine, collidine, quinoline, triethylamine, Tri-n-Propylamine, N, N- dimethyl benzylamine, n,N-Dimethylaniline, 1,8- diaza-bicyclo (5,4,0) -7- endecatylene (hereinafter referred to as DBU), 1,4- diaza-bicyclo (2,2,2) decane (hereinafter referred to as DBO) or 1,5- diaza-bicyclo (4,3,0) nonyl- 5- alkene (hereinafter referred to as DBN).The amount ranges of alkali can use about 0.5 to 3 mole of alkali for every 1 mole compound (II).

The above-mentioned preferred example of oxidant, including halogenating agent, such as chlorine, bromine, iodine, N-chlorosuccinimide, N-bromosuccinimide, N- bromo acetamide, N- bromo phthalimide or toluene-sodium-sulfonchloramide;And sulfonic acid chloride class, such as sulfonic acid chloride, benzene sulfonyl chloride, paratoluensulfonyl chloride or mesyl chloride.

When the reaction carries out in the presence of alkali, the solubility of compound (II) is improved, thus so that reaction is carried out more gentle, but also reduce the yield of by-product.

As starting material compound (II) can in the presence of a base isomerization and in the form of compound as follows exist:

R in formula₁, R₂, R₃Definition with Z with it is as described above identical;M⁺For alkali metal ion, 1/2 X⁺⁺(X is alkaline-earth metal in formula) or ammonium ion.

Referring to structure above, M⁺The example of alkali metal in representative alkali metal ion includes lithium, sodium and potassium.In 1/2 X⁺⁺The specific example of alkaline-earth metal representated by middle X, including magnesium, calcium and barium.The specific example of ammonium ion, including protonated trimethylamine.After being separated compound (II ') with method known per se, which can be used as the starting material of this ring-closure reaction.

Reaction can select in the range of about -60 DEG C to about 100 DEG C, but typically about -20 DEG C to about 50 DEG C.Reaction time is extremely short, and for example, about 5 minutes to about 2 hours.In many cases, reaction is almost completed at the same time with the addition of oxidant.

With thin-layer chromatography, the technologies such as high-speed liquid chromatography can be readily determined the terminal of reaction.When the compound (I) obtained in aforementioned manners includes free carboxy acid, salt can be translated by conventional process with alkali.Institute can be such as sodium salt, sylvite, aluminium salt or calcium salt at salt.When compound obtained (I) is at carboxylate form, free carboxy acid can be translated by conventional process.Compound (I) can be separated and be purified with method known per se, these methods include such as concentration, reduced pressure, vacuum distillation, solvent switch, solvent extraction, crystallization, recrystallization or/and chromatography.

Compound (II) can be used as the starting material of prepare compound (I).But compound (II) itself also shows that activity of weeding to rice field and upland weeds, therefore also can be used as crop, such as the selective herbicide of rice or wheat, although its activity of weeding is not very strong.

Compound (II) can be prepared with any preparation method in following 1 to 3.

Preparation method 1

In above-mentioned reaction equation, R₁, R₂, R₃Definition with Z with it is as described above identical, and Xa is different Thiocyanato or single or double (phenoxy group thiocarboxyl group) amidos.

In this reaction, the dosage of compound (IV) is that every mole compound (III) uses about 0.8 to about 3 mole, preferably about 0.9 to about 1.3 mole compounds (IV).

This reaction be usually to the reaction at being carried out in inert solvent.The specific example of solvent includes aromatic hydrocarbons, such as benzene, toluene or dimethylbenzene;Halogenated hydrocarbon, such as methylene chloride, chloroform or carbon tetrachloride;Ethers, such as ether, isopropyl ether, dioxanes or tetrahydrofuran;Nitrile, such as acetonitrile or propionitrile;Esters, such as ethyl acetate;Hydro carbons, such as petroleum ether, benzin or hexane;And ketone, such as acetone or methyl ethyl ketone.These solvents can be used alone or be used with two kinds or more of form of mixtures.

This reaction can carry out in the presence of alkali.Suitable alkali is organic base, such as trialkyl replaces amine, and alkyl has 1 to 6 carbon atom (such as trimethylamine perhaps triethylamine) or tertiary amine (such as pyridine, γ-collidine, DBU, DBO or DBN;And inorganic base, such as alkali metal hydroxide (such as potassium hydroxide or sodium hydroxide), alkaline earth metal hydroxide (such as calcium hydroxide), alkali carbonate (such as potassium carbonate or sodium carbonate), alkali metal hydrogencarbonate (such as saleratus perhaps sodium bicarbonate) or alkaline earth metal carbonate (such as calcium carbonate).

The dosage of alkali used is that every 1 mole compound (IV) uses about 0.8 to about 1.2 mol alkali.

Reaction temperature can select in the range of about 0 DEG C to about 150 DEG C, but preferably reaction temperature is about 10 DEG C to about 60 DEG C.Reaction can be completed within about 30 minutes to about 10 hours.Reaction end can use thin-layer chromatography, and the technologies such as high-speed liquid chromatography determine.

Preparation method 2

In above-mentioned reaction equation, R₁, R₂, R₃Definition with Z with it is as described above identical.

In this reaction, the dosage of compound (V) is that every 1 mole compound (VI) uses about 0.8 to about 3 mole, it is best to use about 0.9 to about 1.3 mole compound (V).

This reaction be usually to the reaction at being carried out in inert solvent.The specific example of solvent includes aromatic hydrocarbons, such as benzene, toluene or dimethylbenzene;Halogenated hydrocarbon, such as methylene chloride, chloroform or carbon tetrachloride;Ethers, such as ether, isopropyl ether, dioxanes or tetrahydrofuran;Nitrile, such as acetonitrile or propionitrile;Esters, such as ethyl acetate;Hydro carbons, such as petroleum ether, benzin or hexane;And ketone, such as acetone or methyl ethyl ketone.These solvents can be used alone or use as a mixture.

This reaction can carry out in the presence of alkali.The specific example of alkali used is organic base, such as DBU, DBO, DBN, triethylamine, Tri-n-Propylamine or pyridine and inorganic base, such as amide sodium or sodium hydride.

The dosage of alkali used is the alkali that every 1 mole compound (V) uses about 0.8 to about 1.2 mole.

Reaction temperature can select in the range of about 0 DEG C to about 150 DEG C, but preferably reaction temperature is about 10 DEG C to about 100 DEG C.Reaction can be completed within about 30 minutes to about 10 hours.Reaction end can use thin-layer chromatography, and the technologies such as high-speed liquid chromatography determine.

Preparation method 3

(in compound (II), R₁Definition it is same as above;Z is H, and R₂And R₃Respectively lower alkoxy.)

In above-mentioned reaction equation, R₁Definition it is same as above;Hal is halogen, such as chlorine or bromine.R₂Or R₃Representative lower alkoxy with to R₁Definition it is identical.

The first step of this reaction is to react compound (III) with the process of prepare compound (VIII) with compound (VII).

The dosage of compound (VII) is the compound (VII) that every 1 mole compound (III) uses about 0.8 to about 2 mole.

This reaction be to the reaction at being carried out in inert solvent.

The specific example of solvent for use includes aromatic hydrocarbons, such as benzene, toluene or dimethylbenzene;Halogenated hydrocarbon, such as methylene chloride, chloroform or carbon tetrachloride;Ethers, such as ether, isopropyl ether, dioxanes or THF;Nitrile, such as acetonitrile or propionitrile;Esters, such as ethyl acetate;And hydro carbons, such as petroleum ether, benzin or hexane.These solvents can be used alone, or with the use of its form of mixtures.

This reaction can carry out in the presence of alkali.The specific example of alkali used, including organic base, such as trialkyl replace amine, and alkyl has 1 to 6 carbon atom, such as trimethylamine perhaps triethylamine or tertiary amine, such as pyridine, γ-collidine, DBU, DBO or DBN;And inorganic base, such as alkali metal hydroxide, such as potassium hydroxide or sodium hydroxide, alkaline earth metal hydroxide, such as calcium hydroxide, alkali carbonate, such as potassium carbonate or sodium carbonate, alkali metal hydrogencarbonate, such as saleratus or sodium bicarbonate, or alkaline earth metal carbonate, such as calcium carbonate.

The dosage of alkali used is that every 1 mole compound (VII) uses about 0.8 to about 1.2 mole.

Reaction temperature can select within the scope of about 0 DEG C to about 100 DEG C.Reaction time is about 1 hour to about 10 hours.

It can be directly in the form of reaction mixture or after being separated and being refined with conventional method known per se, then carry out with the compound (VIII) being achieved in that the reaction of next step.

The second step of this reaction is to react compound (VIII) with the process of prepare compound (II) with lower alcohol, in compound (II), R₁Definition it is same as above;R₂And R₃Respectively lower alkoxy.

In this reaction, as lower alcohol, the alcohols with 1 to 6 carbon atom, such as methanol, ethyl alcohol, normal propyl alcohol, the tert-butyl alcohol or n-hexyl alcohol can be used.

The dosage of lower alcohol can use about 2 to 10 moles of lower alcohol for every 1 mole compound (VIII).In addition it is also possible to be used using a large amount of excessive alcohol or as solvent.

This reaction can to the reaction at being carried out in inert solvent.The specific example of solvent for use, including aromatic hydrocarbons, such as benzene, toluene or dimethylbenzene;Halogenated hydrocarbon, such as methylene chloride, chloroform or carbon tetrachloride;Ethers, such as ether, dioxanes or tetrahydrofuran;Ketone, such as acetone or methyl ethyl ketone;Nitrile, such as acetonitrile or propionitrile;Amides, such as DMF, DMAC or HMPA;Esters, such as methyl acetate or ethyl acetate;And sulfoxide type, such as DMSO.These solvents can be used alone or with the use of its form of mixtures.

Reaction temperature can be about room temperature (about 15 DEG C) to about 120 DEG C.Reaction time is about 30 minutes to about 10 hours.

Resulting compound (II) is separated and is purified with method known per se, these methods include for example be concentrated, be concentrated under reduced pressure, vacuum distillation, adjustment PH, solvent switch, solvent extraction, crystallization, recrystallization or/and chromatography.

Pyrazoles sulfonamide shown in structural formula (III) is the starting material of the preparation method 1 to 3 of compound (II), can be made with method known per se or its similar approach.Compound (III) can be used method as follows to prepare:

In above-mentioned reaction equation, R₁It is same as above with the definition of Hal;Y is hydrogen, low alkyl group or aralkyl;Z^-For halogen ion or 1/2 SO₄ ^--.By the Y low alkyl group represented and aralkyl and by Z^-The definition of halogen in the halogen ion of representative is same as above.

Compound (Ⅺ) in above-mentioned reaction process is the important intermediate compound of prepare compound (I).The present inventor has invented a kind of brand-new preparation method after studying, wherein can be easy to and the compound is made in high productivity;As a result, it has been found that by compound (Ⅸ) diazotising (the 1st process), then in the presence of metallic catalyst by the diazonium compound be converted to compound (Ⅺ) (the 2nd process) can high productivity the compound is made.By this method of prepare compound (Ⅺ), compound (Ⅺ) can be easy to and high-purity and high productivity obtain, therefore this is highly useful to industrial popularization and application.

1st process is that compound (Ⅸ) is carried out to diazotising with prepare compound (Ⅹ).

This reaction can react compound (Ⅸ) to complete with diazo reagent.The specific example of diazo reagent is alkali metal nitrites salts class (such as potassium nitrite perhaps sodium nitrite) nitrous acid ester (such as isoamyl nitrite or nitrous ether (ethyl nitrite)), nitrosyl sulphuric acid, nitrous acid gas etc..The dosage of diazo reagent is that every 1 mole compound (Ⅸ) uses about 0.8 to about 1.2 mole.

This reaction can to the reaction at being carried out in inert solvent.The specific example of solvent, including water;Organic aliphatic carboxylic acid, such as formic acid or acetic acid;Inorganic acid, such as hydrochloric acid, hydrobromic acid, sulfuric acid or phosphoric acid;And alcohols, such as methanol, ethyl alcohol, normal propyl alcohol or isopropanol.These solvents can be used alone or be used with two kinds or more of form of mixtures.

This reaction generally carries out in acid condition.Acid, such as inorganic acid such as sulfuric acid, hydrochloric acid or hydrobromic acid can be added, when necessary to maintain its acid condition.In this case, sour dosage is generally every 1 mole compound (Ⅸ) and uses about 1 to about 3 mole, but a large amount of excessive acid also can be used.

Reaction temperature is about -20 DEG C to about 40 DEG C, preferably about -10 DEG C to about 5 DEG C.

The reaction is generally completed within about 5 minutes to about 12 hours, and certain reaction time will also change with the adding rate of diazotization agent.

Directly it can be separated in the form of a solution or in (such as crystallization) by known method and then resulting compound (Ⅹ) next process will be transferred to above.

2nd process is to convert compound (Ⅺ) for compound (Ⅹ) in the presence of having metallic catalyst.

When compound (Ⅹ) contains Z^-When representative halogen ion, reaction is the reaction for decomposing compound in the presence of having metallic catalyst.The specific example of metallic catalyst, including transition metal, such as copper, cobalt or zinc, its halide (such as chloride perhaps bromide) its inorganic acid salt (such as sulfate or nitrate), its organic carboxylate (such as acetate) and its hydroxide.The dosage of these metallic catalysts can use about 0.01 to about 3 mole for every 1 mole compound (Ⅹ).When compound (Ⅹ) contains Z^-1/2 representative SO₄ ^--When, reaction is with halogenating agent by compound (Ⅹ) halogenation.As halogenating agent, metal halide as described above, such as copper chloride or copper bromide can be used.In this case, the dosage of halogenating agent can use about 1 to about 3 mole for every 1 mole compound (Ⅹ).This reaction to the reaction at being carried out in inert solvent.The specific example of solvent for use, including water;Organic carboxyl acid, such as formic acid, acetic acid or propionic acid;Inorganic acid, such as hydrochloric acid, hydrobromic acid or sulfuric acid;And alcohols, such as methanol, ethyl alcohol, normal propyl alcohol or isopropanol.These solvents can be used alone, and form of mixtures that can also be two kinds or more of uses.

This reaction generally carries out in acid condition.The acid that can be used to maintain the acid condition of reaction mixture includes inorganic acid, such as hydrochloric acid, hydrobromic acid, sulfuric acid or phosphoric acid;Perhaps organic acid such as formic acid, acetic acid or propionic acid.These acid also act as solvent.

This reaction preferably carries out under the conditions of having existing for sulfur dioxide.In this reaction, by adding sulfur dioxide, compound (Ⅺ) can be made with high yield and high-purity.The dosage of sulfur dioxide is that every 1 mole compound (Ⅹ) uses about 0.3 to about 3 mole.But a large amount of excessive sulfur dioxide also can be used.

Sulfur dioxide can be directly bubbled among reaction mixture in gaseous form.Can also the compound of sulfur dioxide can be generated in acid condition to addition in compound (Ⅹ) during the reaction.The specific example of the compound of sulfur dioxide can be generated in acid condition, including alkali metal bisulfite (such as sodium hydrogensulfite perhaps potassium bisulfite), ammonium bisulfite alkali metal sulfite (such as sodium sulfite or potassium sulfite), alkaline-earth metal sulfite (such as calcium sulfite or barium sulfite) and ammonium sulfite.

Reaction temperature is about -20 DEG C to about 100 DEG C, preferably about -5 DEG C to about 10 DEG C.Reaction time is about 30 minutes to about 12 hours.

3rd process is that perhaps sulfhydrate or two generation sulfide are reacted with prepare compound (Ⅹ III) by compound (Ⅺ) and compound (Ⅻ).

In compound (Ⅻ), hydrogen sulfide, methyl mercaptan, ethanethio and benzyl mercaptan are preferably used.In sulfhydrate, preferably sodium bisuflide and potassium hydrosulfide.In two generation sulfide, vulcanized sodium, potassium sulfide and ammonium sulfide are preferably used.

The dosage of compound (Ⅻ), sulfhydrate or two generation sulfide is that every 1 mole compound (Ⅺ) uses about 0.5 to about 3 mole, it is best to use about 0.9 to 1.2 mole.

In general this reaction can be carried out leniently in a solvent, the specific example of solvent for use, including acetone, tetrahydrofuran, ethyl acetate, dioxanes, acetonitrile, chloroform, methylene chloride, DMA, DMAC and DMSO.These solvents can be used alone or be used with two kinds or more of form of mixtures in appropriate proportions.

This reaction generally carries out in the presence of alkali.The specific example of alkali used, including alkali metal hydride (such as sodium hydride or lithium hydride), Sodamide, alkali metal hydrogencarbonate (such as sodium bicarbonate perhaps saleratus etc.) and alkali carbonate (such as sodium carbonate or potassium carbonate).Alkali and compound (Ⅻ) equimolar when use.

Reaction temperature is not particularly limited, but typically about 0 DEG C to about 60 DEG C.Reaction time is about 30 minutes to about 3 hours.

When having esterifying carboxyl group as substituent group in compound (Ⅹ III), the esterifying carboxyl group can be converted to free carboxy by hydrolytic process known per se, and when necessary, free carboxy can also be esterified.Hydrolysis can be carried out easily with alkali, such as with sodium hydroxide or potassium hydroxide.The reaction preferably in the presence of having described alkali or its aqueous solution, carries out in solvent, such as water, methanol or ethyl alcohol.Reaction temperature can be in boiling spread of the room temperature (about 15 DEG C) to solvent.The dosage of alkali is that every 1 mole compound (Ⅹ III) uses about 1 to about 6 mole, it is best to use about 3 to about 4 moles.When necessary, can as esterification will in this way made from carboxylic acid be converted into ester.Esterification can carry out by known method.In esterification process, it can be with for example, diazomethane, alcohol (such as methanol, ethyl alcohol, normal propyl alcohol, isopropanol, n-butanol or tert-butyl alcohol) and the sour mixture of (such as hydrochloric acid, sulfuric acid or p-methyl benzenesulfonic acid) and the mixture of thionyl chloride and described alcohol.

When compound (Ⅹ III) has esterifying carboxyl group that can be translated into amide derivatives by the reaction of ammonia or amine when perhaps carboxyl is as substituent group.The specific example of amine used is methylamine, ethamine, propylamine and dimethylamine, diethylamine.This conversion reaction can carry out in a manner known per se; it wherein can be used for example, ammonia or amine and suitable bonding agent, such as dicyclohexyl carbodiimide; the diethylphosphoryl cyanide perhaps mixture of the mixture of the chloro- 1- methyl pyridinium iodide of 2- and ammonia or amine and thionyl chloride.When containing carboxyl as substituent group in compound (Ⅹ III), the carboxyl can be removed by decarboxylic reaction by known method.

This decarboxylic reaction can have inorganic acid, such as a hydrochloric acid, in the presence of hydrobromic acid or sulfuric acid, carry out in solvent, such as water, ethyl alcohol, propyl alcohol or isopropanol.Reaction temperature is reflux temperature of the room temperature to solvent for use.Reaction time is about 1 hour to about 24 hours.

Halogenation routinely, nitrification can be easy to when 3-, 4- perhaps unsubstituted on the position 5- of the compound (Ⅹ III) in its pyrazole ring, and perhaps acylation reaction halogen, nitro or acyl group replace hydrogen atom on the position 3-, 4- or 5-.

4th process is to react compound (Ⅹ III) with prepare compound (Ⅹ IV) with halogenating agent.

The specific example of halogenating agent used, including halogen, such as chlorine, bromine or iodine;Halogen halide, such as lodine chloride, Iodide Bromide or bromine chloride;Secondary halogenohydrin, such as hypochlorous acid, hypobromous acid or hypoiodous acid;And metal, such as sodium, potassium, calcium, barium or copper (cuprous and cupric) hypohalite.

In these reagents, halogen and halogen halide be having an oxidant, such as oxygen perhaps use in the presence of hydrogen peroxide or be used in conjunction with water or acetic acid.

What this reaction usually carried out in a solvent.The specific example of solvent for use, including water;Alcohols, such as methanol, ethyl alcohol, isopropanol, n-butanol or the tert-butyl alcohol;Tetramethylene sulfone;Dioxanes;Tetrahydrofuran;Acetonitrile;Acetone;Chloroform;Methylene chloride;Carbon tetrachloride;Benzene;Toluene;And acetic acid.Reaction temperature is not particularly limited, but typically about 0 DEG C to about 70 DEG C.Reaction can be carried out in the case where being cooled to about -80 DEG C, can also be carried out under the reflux temperature for being heated to solvent for use, this will be depending on the type of halogenating agent used.

This reaction is generally completed within about 30 minutes to about 24 hours.

When compound (Ⅹ III) is as follows the compound of structural formula:

The definition of each symbol is same as above in formula, and the position 4- of pyrazole ring can also be halogenated simultaneously.

5th process is to react compound (Ⅹ IV) with prepare compound (III) with ammonia.

The dosage of ammonia is that every 1 mole compound (Ⅹ IV) uses about 1 to about 100 mole, it is preferred to use about 2 to about 30 moles.

This reaction generally carries out in a solvent.The specific example of solvent for use, including polar solvent, such as water;Alcohols, such as methanol, propyl alcohol or butanol;Dimethyl sulfoxide;DMF;DMAC;Glyme class, such as methyl cellosolve, ethylene glycol dimethyl ether or diethylene glycol dimethyl ether;Dioxanes;Tetrahydrofuran perhaps acetonitrile or its mixture;And these polar solvents and nonpolar solvent, such as the mixture of chloroform or methylene chloride.Reaction temperature is not particularly limited, but is typically about -40 DEG C to about 50 DEG C.Reaction time was a few minutes to about 24 hours.

The compound obtained during the 1st to the 5th can be separated and be purified with method known per se, these methods include for example being concentrated, the concentration of contracting pressure, vacuum distillation, adjustment PH, solvent switch, solvent extraction, crystallization, recrystallization or/and chromatography.

Compound (Ⅺ) can also be easily made with known or known per se method as follows:

Compound (Ⅹ IV) can also be easily made with known or known per se method as follows:

Compound (Ⅸ) and (Ⅹ V) can be readily used in " Advances in Heterocyclic Chemistry ", volume 6, page 347, A.R.Katritzky and A.J.Boulton is compiled, Science Press (Academic Press), New York and London, 1966) method or similar method described in are made.

Compound shown in structural formula (IV) can be easily with method as follows, perhaps in the 143rd No. 686/1976 Japanese Unexamined public patent application or " Tetrahedron ", volume 29, method described in page 691 (1973) etc. or similar method are made:

Isothiocyanic acid sulfonyl ester shown in structural formula (V) can be readily used in " applied chemistry ", international version, and volume 1, page 553 (1962) and volume 4, method described in page 430 (1965) or similar method are made.Structural formula (VI) compound represented can be made by known method.

The present invention is described in more detail with embodiment below.But the present invention is not limited to these embodiments.

The code name used in reference example and embodiment is defined as follows: s: unimodal, d: doublet, t: triplet, q: quartet, m: multiplet.

The numerical value that the mixed solvent of eluent is used as in column chromatography is the volume ratio for participating in each solvent of mixing.

Reference example 1

Chloro- 1, the 3- dimethyl pyrazole -4- carboxylate methyl ester (compound A) of 5-

6 grams of 5- amino -1,3- dimethyl pyrazole -4- carboxylate methyl esters are dissolved in the mixed liquor being made of 12 milliliters of concentrated hydrochloric acids, 12 milliliters of acetic acid and 7 milliliters of phosphoric acid, are then cooled to -4 DEG C to -5 DEG C.The solution for 2.5 grams of sodium nitrites being dissolved in 6 milliliters of water is added dropwise in the mixed liquor in 40 minutes, obtains diazonium salt solution (diazotization).In addition, the solution containing 4 grams of sodium hydrogensulfites in 8.5 grams of water is added dropwise in 35 milliliters of concentrated hydrochloric acids in the case where 3 DEG C to 5 DEG C cooling, 0.9 gram of copper sulfate pentahydrate is then added.The solution of diazonium salt solution obtained above and 4 grams of sodium hydrogensulfites being dissolved in 8.5 milliliters of water is at 0 DEG C -3 DEG C while to be added in the mixture.

This mixture is stirred 1 hour at the same temperature, is then poured into 350 milliliters of ice water, then extracted with chloroform.Extract is successively washed with saturated sodium-chloride water solution, saturated sodium bicarbonate aqueous solution and saturated sodium-chloride water solution, dry with anhydrous sodium sulfate later, is boiled off chloroform, is obtained 6.7 grams of orange oils.This product is evaporated under reduced pressure, the leuco-compounds of 5.8 grams of above-mentioned titles are obtained.Yield 86.7%.

85-89 DEG C of boiling point/0.2-0.3 millimetres of mercury

Infrared spectroscopy ν (liquid film) cm^-1: 1715,1525,1297,

1112,1085,778

Compound listed by table 1 is to be obtained according to from the identical operating procedure of reference example 1 using different copper catalysts.Table 2 lists the physicochemical constant of gained compound (compound B-E).

Table 1

Compound	X1	X2	X3	Copper catalyst type	Yield
						A	CH3	CH3	COOCH3	CUCl	85.8
B	CH3CH3CH3	CH3CH3CH3	COOC2H5COOC2H3COOC2H3	CUSO4·5H2OCUClCUCl	88.289.680.5*
						C	CH3	H	COOC2H3	CUCl	79.3
D	(CH3)2CH	CH3	COOCH3	CUCl	66.9
						E	(CH3)2CH	H	COOCH3	CUCl	77.1

^*: the pyrazole compound of starting carries out diazotising after being dissolved in the mixed liquor being made by concentrated hydrochloric acid and water (1: 8 volume ratio).

Table 2

Compound boiling point (fusing point) infrared spectroscopy ν (cm^-1)

No

97-98 DEG C/0.3 millimeter B (liquid film)

Mercury column (38.5-39 °) 1708,1528,1295,

1242,1122,1085

778

The millimetres of mercury of C 80-82 DEG C/0.2 (liquid film)

1715,1540,1408,

1225,1042,772

D (60-61 DEG C) (atoleine (Nujol))

1717,1521,1103,

1289,1231,774

E-(liquid film)

1720,1540,1247,1220

Reference example 2

The chloro- 1- methylpyrazole -4- carboxylic acid, ethyl ester (compound C) of 5-

23.7 grams of 5- amino -1- methylpyrazole -4- carboxylic acid, ethyl esters are dissolved in the mixed liquor being made of 50 milliliters of concentrated hydrochloric acids, 34 milliliters of acetic acid and 28 milliliters of phosphoric acid.At -4 DEG C -- in the solution for 10 grams of sodium nitrites being dissolved in 25 milliliters of water is added dropwise in the mixture in 35 minutes under cooling down and stir at 5 DEG C, diazonium salt solution is made in this way under 3 DEG C of -4 DEG C of coolings, in being added dropwise to diazonium salt solution in 45 minutes in 140 milliliters of concentrated hydrochloric acids containing 13.9 grams of stannous chlorides.This mixture is stirred 1 hour at the same temperature, is subsequently poured into 2 liters of ice water, is extracted with ethyl acetate.Extract is successively washed with sodium-chloride water solution, saturated sodium bicarbonate aqueous solution and the saturated sodium chloride solution of saturation, dry with anhydrous sodium sulfate later.Decompression boils off ethyl acetate.Residue silica gel column chromatography, which purifies, (eluent: ethyl acetate: toluene=1: 1), obtains the compound of 11.7 grams of above-mentioned titles.Yield: 44.3%.

Reference example 3

Chloro- 1, the 3- dimethyl pyrazole -4- carboxylic acid, ethyl ester (compound B) of 5-

According to operating procedure identical with reference example 2, the compound of 6.5 grams of above-mentioned titles is made with 9.2 grams of 5- amino -1,3- dimethyl pyrazole -4- carboxylic acid, ethyl esters.

Yield: 64.4%.

Reference example 4

The chloro- 1- methylpyrazole -4- carboxylate methyl ester of 5-

12.1 grams of 5- amino -1- methylpyrazole -4- carboxylate methyl esters are dissolved in the mixed liquid being made of 28 milliliters of concentrated hydrochloric acids, 18 milliliters of acetic acid and 15.6 milliliters of phosphoric acid closes.On one side at -5 DEG C -- it cools down and stirs at 7 DEG C, be added in the mixture in 5.5 grams of sodium nitrites are dissolved in the solution formed in 7 milliliters of water in 35 minutes on one side, diazonium salt solution is made.In addition, 1.6 grams of stannous chlorides are added in 95 milliliters of acetic acid with sulphur dioxide saturation at 0 DEG C -3 DEG C.Diazonium salt solution obtained above is added dropwise in this solution in 30 minutes.This reaction mixture is stirred 2 hours at 0 DEG C to 4 DEG C, is then poured into 500 milliliters of water, then extracted with ether.Extract is successively washed with saturated sodium-chloride water solution, saturated sodium bicarbonate aqueous solution and saturated sodium-chloride water solution, then dry with anhydrous sodium sulfate.Ether is steamed, 11.6 grams of yellow oils are obtained.After this grease is dissolved in hot water, cooling solution.Separate colorless needle crystals object.Filtering for crystallizing object and drying obtain the compound of 11.2 grams of above-mentioned titles.

Yield 82.3%.

69-70 DEG C of fusing point.

Infrared spectroscopy ν (atoleine) cm^-1: 1720,1540,1227,1042,

772

Reference example 5

5- benzylthio -1,3- dimethyl pyrazole -4- carboxylic acid, ethyl ester

By 2.3 grams of 60%(weight) sodium hydride oil solution washs with pentane, it is subsequently added into 30 milliliters of dimethylformamides (DMF).In the case where 10 DEG C or less cooling, 7.2 grams of benzyl mercaptans are added in this mixture, then in the solution that chloro- 1, the 3- dimethyl pyrazole -4- carboxylic acid, ethyl ester (compound B) of 11.7 grams of 5- being dissolved in 10 milliliters of dimethylformamides is added in 50 minutes under 0 DEG C of -8 DEG C of cooling.Reaction mixture is stirred 1 hour at such a temperature, is then stirred at room temperature 30 minutes, then be poured into 300 milliliters of water.The crystal of precipitating is collected with filtering method, and is dried after being washed with water, to obtain the compound of 15.7 grams of above-mentioned titles.51-53 DEG C of fusing point.

The compound is recrystallized with n-hexane, obtains colourless crystallization object, and fusing point is 57-58 DEG C.

Infrared spectroscopy ν (atoleine) cm^-1: 1700,1505,1250,

1130

Reference example 6

Mono- dimethyl pyrazole -4- carboxylic acid, ethyl ester of 5- chlorosulfonyl -1,3-

31.5 grams of 5- benzylthio -1,3- dimethyl pyrazole -4- carboxylic acid, ethyl esters obtained in reference example 5 are dissolved in 200 milliliters of acetic acid, then plus 125 milliliters of water.It cools down and stirs at 1 DEG C -4 DEG C, and be passed through chlorine into the mixture and be bubbled 50 minutes.Reaction mixture stirs 40 minutes at 0 DEG C, is then poured into 1 liter of ice water.This mixture is extracted with ethyl acetate, is washed with saturated sodium-chloride water solution, then dry with anhydrous magnesium sulfate.Ethyl acetate is steamed, residue is evaporated under reduced pressure, obtains the compound of 26.4 grams of above-mentioned titles, 115-119 DEG C of boiling point/0.25-0.3 millimetres of mercury.

Infrared spectroscopy ν (liquid film) cm^-1: 1724,1392,1255,1190,

1115

Reference example 7

5- amino-sulfonyl -1,3- dimethyl pyrazole -4- carboxylic acid, ethyl ester

4.6 grams of 5- chlorosulfonyl -1,3- dimethyl pyrazole -4- carboxylic acid, ethyl esters are dissolved in 8 milliliters of tetrahydrofurans, this solution is added dropwise in 25 milliliters of ammonium hydroxide at 5 DEG C -7 DEG C.This reaction mixture is stirred 1 hour at the same temperature, is then concentrated to dryness.Ethyl acetate is added in this residue, is then filtered to remove impurity, then filtrate is concentrated under reduced pressure.Residue is diluted with n-hexane, is then cooled with ice, obtains crystal, then this crystal is filtered and is dried, obtains the compound of 3.6 grams of above-mentioned titles.112-113 DEG C of fusing point.

Infrared spectroscopy ν (atoleine) cm^-1: 3350,3240,1690,

1513,1355

Reference example 8

5- benzylthio -1,3- dimethyl pyrazole -4- carboxylic acid

The mixture being made of 5- benzylthio -1, the 3- dimethyl pyrazole -4- carboxylic acid, ethyl ester obtained in reference example 5 of 100 milliliters of ethyl alcohol, 7.8 grams of potassium hydroxide and 35.0 grams flow back while stirring 5 hours.After steaming ethyl alcohol, methylene chloride is added in this residue, acquired solution is extracted with water.This aqueous solution is acidified to PH2 with dilute hydrochloric acid, then is extracted with dichloromethane, it is then dry with anhydrous sulphur sodium.Methylene chloride is steamed, the compound of 27.7 grams of above-mentioned titles is obtained.

Nuclear magnetic resonance (d₆- DMSO) δ ppm:2.30(3H, S), 3.40(3H, S)

4.12(2H, S), 7.00 arrive

7.40(5H, m)

Reference example 9

5- benzylthio -1,3- dimethyl pyrazole -4- carboxylic acid isopropyl

27.7 grams of 5- benzylthio -1,3- dimethyl pyrazole -4- carboxylic acids obtained in reference example 8, the mixture of 150 milliliters of thionyl chlorides and 1.5 milliliters of dimethylformamides composition carries out reflux 5 hours.This mixture is concentrated under reduced pressure, residue is dissolved in 15 milliliters of methylene chloride, the dichloromethane solution is added dropwise in 75 milliliters of isopropanols at 10 DEG C.It after reaction mixture is stirred 4 hours, is concentrated under reduced pressure, then purifies (eluent: hexane: ethyl acetate=5: 1) with silica gel column chromatography.Obtain the oily compound of 18.3 grams of above-mentioned titles.

Nuclear magnetic resonance (CDCl₃) δ ppm:1.35(3H, s), 1.45(3H, s)

2.43(3H, s), 3.49(3H, s),

4.08(2H, s), 5.29(1H, m),

6.90-7.30(5H, m)

Reference example 10

5- sulfamoyl -1,3- dimethyl pyrazole 4- carboxylic acid isopropyl

According to identical operating procedure in reference example 6 and 7, the compound of above-mentioned title is made in 5- benzylthio -1,3- dimethyl pyrazole -4- carboxylic acid isopropyl obtained in reference example 9.120-122 DEG C of fusing point.

Nuclear magnetic resonance (CDCl₃) δ ppm:1.32(3H, s), 1.43(3H, s),

2.40(3H, s), 4.10(3H, s),

5.25(1H, m), 5.97(2H, broad peak s)

Reference example 11

5- sulfamoyl -1,3- dimethyl pyrazole -4- n-propyl carboxylate

According to operating procedure identical with reference example 9 and 10, the oily compound of above-mentioned title is made with 5- benzylthio -1,3- dimethyl pyrazole -4- carboxylic acid.

Nuclear magnetic resonance (CDCl₃) δ ppm:1.02(3H, t), 1.72(2H, m),

2.43(3H, s), 4.12(3H, s),

4.29(2H, t), 6.25(2H, broad peak s)

Reference example 12

5- sulfamoyl -1,3- dimethyl pyrazole -4- carboxylic acid tert-butyl ester

According to operating procedure identical with reference example 9 and 10, the oily compound of above-mentioned title is made in 5- benzylthio -1,3- dimethyl pyrazole -4- carboxylic acid obtained in reference example 8.

Nuclear magnetic resonance (CDCl₃) δ ppm:1.60(9H, s), 2.40(3H, s),

4.10(3H, s), 6.40(2H, s)

Reference example 13

5- sulfamoyl -1,3- dimethyl pyrazole -4- synthesis

According to operating procedure identical with reference example 9 and 10, the oily compound of above-mentioned title is made in 5- benzylthio -1,3- dimethyl pyrazole -4- carboxylic acid obtained in reference example 8.

Nuclear magnetic resonance (CDCl₃) δ ppm:0.90-1.90(7H, m)

2.40(3H, s), 4.10(3H, s),

4.30(2H, s), 6.35(2H, s)

Reference example 14

5- sulfamoyl -1- isopropyl -3- methylpyrazole -4- carboxylate methyl ester

According to operating procedure identical with reference example 5-7, the compound of above-mentioned title is made with the chloro- 1- isopropyl -3- methylpyrazole -4- carboxylate methyl ester (compound D) of 5-.

Infrared spectroscopy ν (atoleine) cm^-1: 3370,3270,1698,

1450,1112

Reference example 15

5- sulfamoyl -1- isopropyl -3- methylpyrazole -4- carboxylic acid, ethyl ester

According to identical operating procedure in reference example 8-10, the compound of above-mentioned title is made with the chloro- 1- isopropyl -3- methylpyrazole -4- carboxylate methyl ester (compound D) of 5-.

Infrared spectroscopy ν (atoleine) cm^-1: 3330,3250,1690,

1372,1111

Reference example 16

The different sulphur cyanato- -4- methoxyl group -6- methylpyrimidine of 2-

4.2 grams of 4- methoxyl group -6- methyl -2- trimethyl silyl aminopyrimidines and 3.5 grams of chloro carbothionic acid phenyl esters are added in 30 milliliters of toluene, heats and is stirred at mixture 5.5 hours at 80 DEG C.After being cooled to room temperature reaction mixture, sediment is removed with filtration method, then filtrate is concentrated under reduced pressure.Residue silica gel column chromatography, which purifies, (eluent: EtOAc: toluene=1: 3), obtains the compound of 2.3 grams of above-mentioned titles.

54-55 DEG C of fusing point.

Infrared spectroscopy ν (atoleine) cm^-1: 1990,1595,1560,

1350,1200,1045

Reference example 17

N-(4.6- dimethoxypyridin -2- base) thionic phenyl carbamate

1 gram of 2- amino-4,6-dimethoxy pyrimidine is added in 10 millimeters of tetrahydrofurans.It is stirred at room temperature, and 0.82 gram of chloro carbothionic acid phenyl ester is added dropwise in 5 minutes in this mixture, then flow back 7 hours.After the reaction mixture was cooled to room temperature, insoluble matter is filtered out, filtrate is concentrated under reduced pressure.Residue purifies (eluent: chloroform) with silica gel column chromatography, obtains the compound of 0.1 gram of above-mentioned title.

114 DEG C of fusing point

Infrared spectroscopy ν (atoleine) cm^-1: 3200,1605,1530,

1325,1195

Reference example 18

The different sulphur cyanato- pyrimidine of 4,6- dimethoxy -2-

45 grams of 4,6- dimethoxy -2- trimethyl silyl aminopyrimidines and 35 grams of chloro carbothionic acid phenyl esters are added in 300 milliliters of acetonitriles, then this mixture flows back 10 hours.This reaction mixture is concentrated under reduced pressure again to remove acetonitrile, then 300 milliliters of toluene are added in residue.Insoluble matter is removed with filtration method, filtrate is concentrated under reduced pressure, residue purifies (eluent: ethyl acetate: hexane=1: 1) with silica gel column chromatography.

17 grams of different sulphur cyanato- pyrimidines of 4.6- dimethoxy -2- are obtained from first elution liquid.

85-86 DEG C of fusing point

Infrared spectroscopy ν (liquid film) cm^-1: 1995

3.5 grams of 2- (bis- (phenoxythiocarbonyl) amino of N, N-) -4,6- dimethoxypyridin is obtained from second of eluent.

127-128 DEG C of fusing point

Infrared spectroscopy ν (atoleine) cm^-1: 1600,1295,1190

Reference example 19

The different sulphur cyanato- pyrimidine of 4,6- dimethyl -2-

According to operating procedure identical with reference example 18, the pale yellowish oil compound of above-mentioned title is made with 4,6- dimethyl -2- trimethyl silyl aminopyrimidine and chloro carbothionic acid phenyl ester.

117-118 DEG C of boiling point/2 millimetress of mercury

Infrared spectroscopy ν (liquid film) cm^-1: 1995

Reference example 20

The different sulphur cyanato- -1,3,5-triazines of 4- methoxyl group -6- methyl -2-

15 grams of 4- methoxyl group -6- methyl -2- trimethyl silyl amino -1,3,5-triazines and 12.2 grams of chloro carbothionic acid phenyl esters are added in 50 milliliters of dimethylbenzene.This mixture is stirred 6.5 hours at about 140 DEG C.After this reaction mixture is cooled to room temperature, insoluble matter is filtered out, and filtrate is concentrated under reduced pressure.Residue silica gel column chromatography, which purifies, (eluent: ethyl acetate: toluene=1: 3), obtains the oily compound of 3 grams of above-mentioned titles.

Infrared spectroscopy ν (liquid film) cm^-1: 1970

Reference example 21

The different sulphur cyanato- -1,3,5-triazines of 4,6- dimethyl -2-

According to operating procedure identical with reference example 20, the pale yellowish oil compound of above-mentioned title is made with 4,6- dimethyl -2- trimethyl silyl amino -1,3,5-triazines and chloro carbothionic acid phenyl ester.

Infrared spectroscopy ν (liquid film) cm^-1: 1960

Reference example 22

N-(1,3- dimethyl -4- methoxycarbonyl group -5- pyrazoles sulfonyl)-N '-(4,6- dimethoxy -2- pyrimidine radicals) thiocarbamide (compound a)

6.4 grams of 5- sulfamoyl -1,3- dimethyl pyrazole -4- carboxylate methyl esters and 5.6 grams of different sulphur cyanato- pyrimidines of 4,6- dimethoxy -2- obtained in reference example 18 are added in 150 milliliters of acetone, and are stirred 12 hours at 43 DEG C -45 DEG C.

Reaction mixture is cooled with ice, the crystal of precipitating is collected with filtration method.After resulting crystal is suspended in 300 milliliters of water, this mixture is adjusted to PH2 with hydrochloric acid.The crystal filtered to isolate is washed with water and dries, and obtains 9.9 grams of crystals.With the compound for obtaining 8.4 grams of above-mentioned titles after acetone recrystallization.

149-150 DEG C of fusing point

Infrared spectroscopy ν (atoleine) cm^-1: 3180,1720,1660,13701200,1170,1185

Reference example 23

N-(1,3- dimethyl -4- carbethoxyl group -5- pyrazoles sulfonyl)-N '-(4- methoxyl group -6- methyl -2- pyrimidine radicals) thiocarbamide (compound b)

1.96 grams of 5- sulfamoyl -1,3- dimethyl pyrazole -4- carboxylic acid, ethyl esters and the different sulphur cyanato- -4- methoxyl group -6- methylpyrimidine of 1.44 grams of 2- obtained in reference example 15 are dissolved in 30 milliliters of acetonitriles.It stirs and is cooled with ice on one side, 1.21 grams of DBU are added dropwise in the solution on one side, according to being stirred at room temperature 5 hours.Reaction mixture is poured into 150 milliliters of water, mixture is then adjusted to PH2 with hydrochloric acid.The crystal filtered to isolate is washed with water and dries, obtains crystal.With the colourless crystallization compound for obtaining 0.25 gram of above-mentioned title after acetone recrystallization.

157-158 DEG C of fusing point

Infrared spectroscopy ν (atoleine) cm^-1: 3170,1708,1612,1362

1255,1195,1178

Nuclear magnetic resonance (CDCl₃) δ ppm:1.27(3H, t), 2.40(3H, s)

2.52(3H, s), 4.02(3H, s),

4.21(2H, q), 4.29(3H, s)

6.37(1H, s), 8.82(1H, broad peak s)

Reference example 24

N-(1,3- dimethyl -4- ethoxy carbonyl -5- pyrazoles sulfonyl)-N '-(4,6- dimethoxy -2- pyrimidine radicals) thiocarbamide (compound c)

It will be flowed back 4 hours by the mixture of 1.5 grams of 5- sulfamoyl -1,3- dimethyl pyrazole -4- carboxylic acid, ethyl esters, 2.6 grams of 2- (bis- (phenoxythiocarbonyl) amino of N, N-) -4,6- dimethoxypyridins, 0.8 gram of Anhydrous potassium carbonate and 35 milliliters of acetone compositions.After this mixture is cooled to room temperature, insoluble matter is filtered out, is concentrated filtrate to dry.Residue is dissolved in the mixture of ethyl acetate and toluene, and be allowed to settle, to obtain crystal.Filtering for crystallizing object, and be dissolved in 50 milliliters of water.This solution is adjusted to PH2 with hydrochloric acid, obtains crystal.It is washed with water and dries after crystal is filtered, obtain the compound of 0.4 gram of above-mentioned title.

127-128 DEG C of fusing point

Infrared spectroscopy ν (atoleine) cm^-1: 3200,1715,1605,1528

1362,1205,1192,1183

Nuclear magnetic resonance (CDCl₃) δ ppm:1.28(3H, t), 2.41(3H, s)

4.02(6H, s), 4.23(2H, q)

4.28(3H, s), 5.85(1H, s)

8.64(1H broad peak s)

Table 3 is listed according to the resulting compound of operating procedure identical with example 22-24.

The Me meaning is CH₃, the Et meaning is C₂H₅, the Pr meaning is C₃H₇,

The Bu meaning is C₄H₉(identical in following each column)

Reference example 25

5- benzylthio -4-N, N- formyl-dimethylamino -1,3- dimethyl pyrazole

The mixture of 27.7 grams of 5- benzylthio -1,3- dimethyl pyrazole -4- carboxylic acids as obtained in reference example 8,150 milliliters of thionyl chlorides and 1.5 milliliters of dimethylformamide compositions flows back 5 hours.After this reaction mixture is cooling, decompression steams thionyl chloride, obtains 30.0 grams of grease.

It will be added dropwise to by above-mentioned resulting 12 grams of grease and 5 milliliters of methylene chloride by 17.2 grams of N in 1 hour, in the mixture of TMSDMA N dimethylamine and 50 milliliters of methylene chloride composition, it is cooling at -60 DEG C simultaneously, then this reaction mixture is stirred 3 hours at the same temperature.It stirs on one side, the temperature of reaction mixture was increased to room temperature in 1 hour on one side.Reaction dissolvent is steamed, residue silica gel column chromatography, which purifies, (eluent: ethyl acetate hexane=1: 1), obtains the compound of 6.5 grams of above-mentioned titles.

Nuclear magnetic resonance (CDCl₃) δ ppm:2.22(3H, s), 2.94(3H, broad peak)

3.12(3H, broad peak s), 3.28(3H, s)

3.97(2H, s), 7.00-7.40(5H, m)

Reference example 26

5- benzylthio -1,3- dimethyl pyrazole

Mixture by 2 grams of 5- benzylthio -1,3- dimethyl pyrazole -4- carboxylic acid, ethyl esters, 9 milliliters of concentrated hydrochloric acids and 6 milliliters of water compositions is flowed back 11 hours.Reaction mixture is cooled to room temperature, is extracted with chloroform.Extract liquor is washed with saturated sodium-chloride water solution, dry with anhydrous sodium sulfate.Decompression boils off chloroform, obtains the colorless oil compound of 1.5 grams of above-mentioned titles.

Nuclear magnetic resonance (CDCl₃) δ ppm:2.23(s), 3.51(3H, s),

3.86(2, s), 6.07(1H, s),

7.00-7.35(5H, m)

Reference example 27

Chloro- 1, the 3- dimethyl -5- pyrazoles sulfonamide of 4-

(1) 5 milliliters of water are added to obtained in the reference example 26 and are dissolved in the solution of 1.5 grams of 5- benzylthio -1,3- dimethyl pyrazoles in 15 milliliters of acetic acid.Under 3 DEG C of -4 DEG C of coolings, chlorine is passed through the mixture 15 minutes, chlorine is then passed through the mixture 1 hour at 10 DEG C.Reaction mixture is poured into 100 milliliters of ice water, is extracted with ether.Extract is dry with anhydrous sodium sulfate, and chloro- 1, the 3- dimethyl -5- pyrazoles sulfonic acid chloride of 2 grams of pale yellowish oil 4- is obtained after reduced pressure.

Nuclear magnetic resonance (CDCl₃) δ ppm:2.29(3H, s), 4.15(3H, s)

(2) chloro- 1, the 3- dimethyl -5- pyrazoles sulfonic acid chloride of 2 grams of 4- that above-mentioned (1) obtains is dissolved in tetrahydrofuran, and 25 milliliters of ammonium hydroxide at 8 DEG C -10 DEG C in being added dropwise in the solution in 10 minutes.It stirs 1 hour, this solution is concentrated to dryness, then 30 milliliters of ethyl acetate are added in residue at the same temperature.It is filtered to remove after insoluble matter, filtrate is concentrated, (eluent: ethyl acetate: toluene=2: 1), obtain the compound of 0.45 gram of above-mentioned title with silica gel column chromatography purification.

132-134 DEG C of fusing point

Infrared spectroscopy ν (atoleine) cm^-1: 3350,3210,1545,1358

1345,1180,1132,640,

610

Reference example 28

2- acetyl group 3, bis- (methyl mercapto) ethyl acrylates of 3-

50.0 grams of ethyl acetoacetates are dissolved in 100 milliliters of dimethyl sulfoxides.53.1 grams of potassium carbonate are added in this solution at room temperature, this mixture is stirred 30 minutes.Internal temperature is maintained at 10 DEG C, and 29.3 grams of carbon disulfide are added in said mixture dropwise in 30 minutes, is then stirred 1 hour at 10 DEG C.1200 grams of Methyl iodides are added in this mixture in 30 minutes at the same temperature, and are stirred 1 hour in same temperature.Internal temperature is adjusted to room temperature, then reaction mixture is stirred 1 hour, then is poured into 200 milliliters of ice water, is extracted with dichloromethane.Extract is washed with water, dries and concentrates, and obtains the light brown oil compound of 66.0 grams of above-mentioned titles.

Nuclear magnetic resonance (CDCl₃) δ ppm:1.35(3H, t), 2.38(3H, s),

2.45(6H, s), 4.30(2H, q)

Reference example 29

2- acetyl group -3,3-(benzylthio) ethyl acrylate

35 grams of ethyl acetoacetates are dissolved in 100 milliliters of dimethyl sulfoxides.37.2 grams of potassium carbonate are added in the solution at room temperature, this mixture is stirred 30 minutes.Internal temperature is maintained at 10 DEG C, and 20.5 grams of carbon disulfide are added in said mixture dropwise in 30 minutes, is then stirred 1 hour at 10 DEG C.92 grams of benzyl chlorine in being added dropwise in this mixture in 30 minutes at 10 DEG C.It stirs the mixture for 1 hour, is then stirred at room temperature 2 hours at the same temperature.Reaction mixture is poured into 200 milliliters of ice water, gained crystal is collected by filtration, is washed with water, with ethyl alcohol recrystallization, obtains the crystalline compounds of 69.6 grams of above-mentioned titles, 81.5-82 DEG C of fusing point.

Nuclear magnetic resonance (CDCl₃) δ ppm:1.25(3H, s), 2.14(3H, s),

4.08(4H, s), 4.23(2H, q)

7.29(10H, s)

Reference example 30

1,3- dimethyl -4- ethoxy carbonyl -5- methyl mercapto pyrazoles

Bis- (methyl mercapto) ethyl acrylates of 7.5 grams of 2- acetyl group -3.3- are dissolved in 50 milliliters of acetonitriles.It stirs under room temperature (15 DEG C), and 1.8 grams of methyl hydrazines is added in the solution dropwise in 10 minutes, be then heated at reflux 7 hours.End of reaction, decompression steam solvent.Residue purifies (eluent: n-hexane: ethyl acetate=4/1 to 2/1) with silica gel column chromatography, obtains the oily compound of 4.1 grams of above-mentioned titles.

Nuclear magnetic resonance (CDCl₃) δ ppm:1.38(3H, t), 2.43(6H, s),

3.90(3H, s), 4.35(2H, q)

C₉H₁₄N₂O₂The elemental analysis result of S:

Calculated value (%) C, 50.45;H, 6.59;N, 13.07

Measured value (%) C, 50.44;H, 6.58;N, 13.06

Reference example 31

1,3- dimethyl -4- ethoxy carbonyl -5- benzylthio pyrazoles

Bis- (benzylthio) ethyl acrylates of 10 grams of 2- acetyl group -3,3- are dissolved in 60 milliliters of acetonitriles.It stirs under room temperature (15 DEG C), and 1.2 grams of methyl hydrazines is added in the solution dropwise in 10 minutes, be then heated to reflux 3 hours.Then decompression steams solvent.Residue purifies (elutriant: n-hexane: ethyl acetate=8/1) with silica gel column chromatography, obtains the white crystals thing of 5.8 grams of above-mentioned titles, and 55-56 DEG C of fusing point.

Nuclear magnetic resonance (CDCl₃) δ ppm:1.42(3H, t), 2.42(3H, s)

3.37(3H, s), 4.07(2H, s)

4.37(2H, q), 7.20-7.40

(5H, m)

Infrared spectroscopy ν (atoleine) cm^-1: 1700,1508,700

C₁₅H₁₈N₂O₂The elemental analysis result of S:

Calculated value (%) C, 62.05;H, 6.25;N, 9.65

Measured value (%) C, 62.03;H, 6.20;N, 9.64

Embodiment 1

5,7- dimethoxy -2-(1,3- dimethyl -4- methoxycarbonyl group -5- pyrazoles sulfonyls) imino group -2H-1,2,4- thiadiazoles (2,3-a)-pyrimidine (compound N ol)

4.3 grams of N-(1,3- dimethyl -4- methoxycarbonyl group -5- pyrazoles sulfonyl are added in 50 milliliters of pyridines)-N '-(4,6- dimethoxy -2- pyrimidine radicals) thiocarbamide, at -6 DEG C -- under 8 DEG C of coolings, 1.6 grams of bromines are added in this mixture.It stirs 1.5 hours at the same temperature, reaction mixture is poured into 300 milliliters of water.Resulting crystal is filtered, is washed with water, and is dry.It is recrystallized with acetonitrile, obtains the colourless crystallization compound of 2.8 grams of above-mentioned titles.

C₁₄H₁₆N₆O₆S₂Elemental analysis result:

Calculated value (%) C:39.25;H:3.76;N:19.61

Measured value (%) C:39.44;H:3.77;N:19.81

170-171 DEG C of fusing point

Infrared spectroscopy ν (atoleine) cm^-1: 1715,1625,1465,1365

1100,918,902

Nuclear magnetic resonance (d₆- DMSO) δ ppm:2.21(3H, s), 3.72(3H, s)

4.01(3H, s), 4.04(3H, s)

4.22(3H, s), 6.60(1H, s)

Embodiment 2

5,7- dimethyl -2(1,3- dimethyl -4- carbethoxyl group -5- pyrazoles sulfonyls) imino group -2H-1,2,4- thiadiazoles (2,3-a)-pyrimidine (compound N o2)

Suspend 0.53 gram of N-(1 in 30 ml methanols, 3- dimethyl -4- carbethoxyl group -5- pyrazoles sulfonyl)-N '-(4,6- dimethyl -2- pyrimidine radicals) thiocarbamide, then in 0 DEG C of following stirring, while 0.21 gram of bromine is added dropwise.Then stirring suspension object 30 minutes at the same temperature are stirred at room temperature 30 minutes.The crystal for filtering precipitating, is washed with methanol.The crystal recrystallized from acetonitrile obtains the colourless crystallization compound of 0.26 gram of above-mentioned title.

C₁₅H₁₈N₆O₆S₂Elemental analysis result:

Calculated value (%) C:43.89;H:4.42;N:20.47

Measured value (%) C:44.00;H:4.39;N:20.45

167-168 DEG C of fusing point

Infrared spectroscopy ν (atoleine) cm^-1: 1780,1650,1465,1355

1303,1100,913

Nuclear magnetic resonance (d₆- DMSO) δ ppm:1.24(3H, t), 2.21(3H, s)

2.59(3H, s), 2.69(3H, s)

4.01(3H, s), 4.22(2H, q)

7.35(1H, s)

Embodiment 3

5,7- dimethoxy -2-(1,3- dimethyl -4- carbethoxyl group -5- pyrazoles sulfonyls) imino group -2H-1,2,4- thiadiazoles (2,3-a)-pyrimidine (compound N o3)

Suspend 0.5 gram of N-(1 in 20 ml methanols, 3- dimethyl -4- carbethoxyl group -5- pyrazoles sulfonyl)-N '-(4,6- dimethyl -2- pyrimidine radicals) thiocarbamide, then at -4 DEG C -- 5 DEG C of following stirrings, 0.2 gram of N- bromine succinimide is added in side.This reaction mixture is stirred 25 minutes at the same temperature.The crystal filtered to isolate, is washed with methanol.The crystal recrystallized from acetonitrile obtains the colourless crystallization compound of 0.4 gram of above-mentioned title.

C₁₅H₁₈N₆O₆S₂Elemental analysis result:

Calculated value (%) C:40.72;H:4.10;N:18.99

Measured value (%) C:40.83;H:3.96;N:18.93

157-158 DEG C of fusing point

Infrared ν (atoleine) cm^-1: 1722,1635,1543,1465,

1365,1105,925,912

Nuclear magnetic resonance (d₆- DMSO) δ ppm:1.25(3H, t), 2.20(3H, s)

4.00(3H, s), 4.03(3H, s)

4.22(3H, s), 4.23(2H, q)

6.60(1H, s)

Embodiment 4

5,7- dimethoxy -2-(4- carbethoxyl group -1- methyl -5- pyrazoles sulfonyls) imino group -2H-1,2,4- thiadiazoles (2,3-a)-pyrimidine (compound N o4)

In 20 milliliters of pyridines dissolve 1 gram of N-(4- carbethoxyl group -1- methyl -5- pyrazoles sulfonyl)-N '-(4,6- dimethyl -2- pyrimidine radicals) thiocarbamide (acetonitrile solvent product) sylvite, at -6 DEG C -- under 8 DEG C of coolings, 0.37 gram of bromine is added dropwise in the solution.Reaction mixture is stirred 2 hours at the same temperature, is poured into 100 milliliters of ice water.Resulting crystal is filtered, is washed with water, with recrystallized from acetonitrile, obtains the colourless crystallization compound of 0.5 gram of above-mentioned title.

C₁₄H₁₆N₆O₆S₂Elemental analysis result:

Calculated value (%) C:39.25;H:3.73;N:19.61

Measured value (%) C:39.36;H:3.71;N:19.67

152-153 DEG C of fusing point

Infrared spectroscopy ν (atoleine) cm^-1: 1730,1710,1630,1545,

1465,1362,1215,915

Nuclear magnetic resonance (d₆- DMSO) δ ppm:1.30(3H, t), 4.10(3H, s)

4.18(3H, s), 4.26(3H, s)

4.24(2H, q), 5.91(1H, s),

7.79(1H, s)

Table 4 lists the compound made from operating procedure identical with embodiment 1-4.

Structural formula:

Table 4

Formulation Example 1

Missible oil

Missible oil contains following substance:

Compound N o4:2(weight) %

Dimethylbenzene: 75(weight) %

Dimethylformamide: 18(weight) %

Polyglycol ether (Nonipol 85

): 5(weight) %

(this composition is diluted to debita spissitudo with water using preceding every time)

Formulation Example 2

Wettable powder

Wettable powder is made in mixture by crushing following substance:

Compound N O.10:30(weight) %

Sodium lignin sulfonate: 5(weight) %

Polyoxyethylene glycol ether (Nonipol 85): 5(weight) %

Clay: 55(weight) %

White carbon: 5(weight) %

(every time before use, this composition is diluted to debita spissitudo with water)

Formulation Example 3

Granule

Knead following mixture of substances with water and granule be made:

Compound N o3:0.2(weight) %

Sodium lignin sulfonate: 2(weight) %

Bentonite: 57.8(weight) %

Talcum: 40(weight) %

Formulation Example 4

Granule

Granule is made with the mixture that water kneads following substance:

Compound N o8:1(weight) %

Sodium lignin sulfonate: 5(weight) %

Bentonite: 94(weight) %

Formulation Example 5

Granule

Granule is made with the mixture that water kneads following substance:

Compound c:1(weight) %

Sodium lignosulfonate: 6(weight) %

Bentonite: 93(weight) %

Test example 1

Echinochloa (Echinochloa oryzicola), difformed galingale herb (Cyperus difformis), Monochoria vaginalis (Monochoria vaginalis), Vandellia (Lindernia procumbens), mexicana (Rotala indica), with every kind of firefly Lin (Scirpus juncoides) sowing in 1/5000 acre of Wagner basin containing paddy soils, the paddy soils of the overwintering stem tuber comprising needle spikesedge herb (Eleocharis aricularis) are sprinkling upon in each basin later.Then the rudiment stem tuber of short arrowhead (Sagittaria pygmaea) and Herba Cyperi Glomerati (Cyperus serotinus) respectively with 1 centimetre of depth and with earth surface planting in each basin.Meanwhile the rice shoot of rice (kind: " Manryo ";It is cultivated in individual incubator;2.0 leaflet stages;Plant is 12 centimetres high) it is transplanted in each basin, insertion depth is 3 centimetres, contains 0.2(weight what is produce according to operating procedure identical with Formulation Example 3 later) granule of formula (I) compound of % ratio is directly applied in each basin under the conditions of burying.Every acre in this way spreading 0.5 gram or 1.0 grams of effective ingredients (compound (I)).It is dispensed using concentration with every acre as 2.5% prometryn (granule), 2.5 grams or 5 grams of effective ingredients compare.21 days after application are evaluated by the herbicidal effect and phytotoxicity of each test compound.

Herbicidal effect is by following standard rating (also pressing this standard) in test example 2 shown in below.

Serial number herbicidal effect inhibiting rate (ratio for eliminating weeds) %

0 without 0

1 very weak 0.1-50

2 weak 50.1-70

3 medium 70.1-87.5

The last 4 87.6-99.9

6 is most strong by 100

To the phytotoxicity of rice by following canonical representation (also pressing this standard in test example 2 below).

Serial number phytotoxic damage percentage (%)

0 without 0

1 very little 0.1-12.5

2 small 12.6-30.0

3 medium 30.1-50.0

4 serious 50.1-99.9

5 most serious 100

The result of the expression test example of table 5.

Test example 2

Echinochloa (Echinochloa oryzicola), special-shaped sand-grass (Cyperusdifformis), Monochoria vaginalis (Monochoria vaginalis), Vandellia (Lindernia procumbens), mexicana (Rotala indica), with every kind of firefly Lin (Scirpus juncoides) slotting kind in 1/5000 acre of Wagner basin containing paddy soils, the paddy soils of the overwintering stem tuber comprising needle spikesedge herb (Eleocharis aricularis) are sprinkling upon in each basin later.Then short arrowhead, (the rudiment stem tuber of Sagittaria pygmaea and Herba Cyperi Glomerati (Cyperus serotinus) is respectively with 1 centimetre of depth and with earth surface planting in each basin.Meanwhile the rice shoot of rice (kind: " Manryo ";It is cultivated in individual incubator;2 leaflet stages;Plant is 12 centimetres high) it is transplanted in each basin, insertion depth is 3 centimetres, later and then according to operating procedure identical in Formulation Example 5 produce containing 0.2(weight) granule of molecular formula (I) compound of % ratio is directly applied in each basin under the conditions of burying, every acre in this way spreading 5 grams or 10 grams of effective ingredients (compound (II)).It is compared with such as above-mentioned same way application prometryn granule.The herbicidal effect and phytotoxicity of each compound were evaluated in 21 days after application.

Table 6 lists test result.

Claims (1)

1, contain Herbicidal combinations of the compound shown in following structural formula as effective ingredient:

Wherein R₁For can substituted pyrazolyl；R₂And R₃Respectively C_1-6Alkyl or C_1-6Alkoxy；

R₅For C_1-6Alkyl；R₆For hydrogen or low alkyl group；R₇For the carboxyl being esterified when necessary, halogen, carbamoyl, the latter can use C_1-6Alkyl is monosubstituted or two replace；With

Z is CH or N.