CN1038682C - Cyclic amide compounds, process for their production and their use as herbicides - Google Patents
Cyclic amide compounds, process for their production and their use as herbicides Download PDFInfo
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- CN1038682C CN1038682C CN93112741A CN93112741A CN1038682C CN 1038682 C CN1038682 C CN 1038682C CN 93112741 A CN93112741 A CN 93112741A CN 93112741 A CN93112741 A CN 93112741A CN 1038682 C CN1038682 C CN 1038682C
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- base
- methyl
- phenyl
- benzothiazole
- ethyl
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
- A01N43/86—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms six-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Dentistry (AREA)
- Wood Science & Technology (AREA)
- Plant Pathology (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Agronomy & Crop Science (AREA)
- General Health & Medical Sciences (AREA)
- Pest Control & Pesticides (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pyrrole Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Abstract
The present invention provides a cyclic amide compound of formula (I): wherein R<1> is a phenyl group which may be substituted, R<2> is a hydrogen atom or an alkyl groupe which may be substituted by a halogen atom, and R<3> is functional groups, wherein D is an oxygen atom, a sulfur atom or -N(R<4>)-, wherein R<4> is an alkyl group, a process for producing such a compound, a herbicidal composition containing such a compound as an active ingredient, a herbicidal method and an intermediate for the production of such a compound. The cyclic amide compound of the present invention is useful as a herbicidally active ingredient to selectively kill weeds without presenting a phytotoxicity against crop plants.
Description
The present invention relates to the hereinafter cyclic amide compounds of formula shown (I) compound, its preparation method, it is as weedicide and in order to prepare their used intermediates, herbicidal composition comprises cyclic amide compounds and other weeding activity components, and comprises the herbicidal methods that this class herbicidal composition is applied to plant.
So far, need can be suitable for of a kind of development selectively remove injurious weed extremely and not have toxic weedicide for the cereal crops.A lot of software engineering researchers invent go out this class weedicide, and have announced many selective herbicides, but these might not be satisfactory.In this case, also need to develop a kind of better weedicide.
On the other hand, Japanese unexamined patent publication number 89485/1992 has disclosed the Cydic amide derivatives with weeding activity, but these derivatives are different from the hereinafter The compounds of this invention of formula shown (I) representative on chemical structure.
The present inventor is from developing a kind of target of fabulous weedicide, cyclic amide compounds has been carried out broad research, found that hereinafter formula shown (I) compound has fabulous herbicidal effect and selectivity, can also prevent and treat injurious weed effectively and some crops plant nontoxicity.The present invention finishes on this discovery basis just.
The invention provides the cyclic amide compounds shown in the class formula (I):
R in the formula
1Be phenyl, R
2Be C
1-8Alkyl, and R
3Be to be replaced by halogen atom
Be Sauerstoffatom or sulphur atom, be preferably R
3For can be by halogen atom, C
1-8Alkyl or C
1-8Alkoxyl group replaces
Wherein D is Sauerstoffatom or sulphur atom.
The present invention also provides the method for preparing this cyclic amide compounds, contains the herbicidal composition of this composition, uses the herbicidal methods of these herbicidal composition and is the used intermediate of its preparation.
In above-mentioned formula (I), the substituting group on can substituted phenyl is for R
1, for example can be halogen atom; The alkyl that can be replaced by halogen atom, the alkoxyl group that can be replaced by halogen atom; Alkylthio that can be replaced by halogen atom or the alkane alkylsulfonyl that can be replaced by halogen atom.Equally, commutable
, commutable
, commutable
Commutable
, commutable
, commutable
Commutable
Each substituting group, for R
3For example can be halogen atom; The alkyl that can be replaced by halogen atom; The alkoxyl group that can be replaced by halogen atom, the alkylthio that can be replaced by halogen atom; The alkane alkylsulfonyl that can be replaced by halogen atom; Can be by the aryl of halogen atom or haloalkyl replacement; Can be by the heteroaryl of halogen atom or haloalkane replacement; Can be by the aryloxy of halogen atom or haloalkyl replacement; Or can be by the heteroaryloxy of halogen or haloalkyl replacement.Above-mentioned aryl or part aryl for example can be phenyl or naphthyls, and above-mentioned heteroaryl or part heteroaryl for example can be pyridyl, pyrryl, thienyl or furyl.And these substituting groups can be single or multiple, and with regard to many substituting groups, this class substituting group can be identical or different.And limited commutable
, commutable
, can replace
, commutable
, commutable
, commutable
Commutable
, wherein D defines as defined above, for the R in the formula (I)
3,
Included, furans-2-base for example, furans 3-base, thiophene-2-base, thiene-3-yl-, 1-methylpyrrole-2-base and 1-methylpyrrole-3-base,
Included, thiazol-2-yl ， oxazole-2-base for example, 1-methyl-imidazoles-2-base, thiazole-4-Ji ， oxazole-4-base, 1-Methylimidazole-4-base, thiazole-5 Ji ， oxazole-5-base and 1-ethyl imidazol(e)-5-base;
Included, isothiazole-3-base ， isoxazole-3-base for example, 1-methylpyrazole-3-base, isothiazole-4-base ， isoxazole-5-base ， isoxazole-5-base and 1-methylpyrazole-5-base;
Included, cumarone-2-base for example, cumarone-3-base, thionaphthene-2-base, thionaphthene-3-base, 1 methyl-indoles-2-base and 1-methyl-indol-3-yl;
Ben Bing Evil miaow-2-base for example, benzothiazole-2-base and 1-tolimidazole-2-base;
Comprise, for example, thionaphthene-3-base, benzoxazole-3-base and 1-methyl-benzopyrazoles 3-base.
R in the formula (I)
1, R
2, R
3And R
4Alkyl that is limited or part alkyl for example can be C
1-8Straight or branched alkyl such as methyl, ethyl, propyl group, sec.-propyl, the tertiary butyl, amyl group or octyl group.R
1, R
2Or R
3In halogen atom or can be fluorine as substituent halogen atom, chlorine, bromine or iodine.As substituting group.These halogen atoms can be single or multiple, with regard to major part replaces halogen atom, and can be identical or different.
Hereinafter listed the cyclic amide compounds example of formula (I) preferably.
(1) R
1Be preferably phenyl.
(2) R
2Be preferably the alkyl that is replaced by halogen atom, be more preferably unsubstituted alkyl.
(4) in the cyclic amide compounds of formula (I), be best with following compounds.3-[[1-(benzothiazole-2-yl)-2-methyl) ethyl)-2,3-dihydro-6-methyl-5-phenyl-4H-1,3-azoles piperazine-4-ketone, 3-((1-(5-fluoro benzothiazole-2-yl)-1-methyl) ethyl)-2,3-dihydro-6-methyl-5-phenyl-4H-1,3-oxazine-4-ketone, 3-((1-(7-chloro benzothiazole-2-yl)-1-methyl) ethyl)-2,3-dihydro-6-methyl-5-phenyl-4H-1,3-oxazine-4-ketone, 3-((1-(4-chloro benzothiazole-2-yl)-1-methyl) ethyl)-2,3-dihydro-6-methyl-5-phenyl-4H-1,3-oxazine-4-ketone, 3-((1-(7-bromo benzothiazole-2-yl)-1-methyl) ethyl)-2,3-dihydro-6-methyl-5-phenyl-4H-1,3-oxazine-4-ketone, 3-((1-(7-chloro benzothiazole-2-yl)-1-methyl) ethyl)-6-ethyl-2,3-dihydro-5-phenyl-4H-1,3-oxazine-4-ketone, 2,3-dihydro-6-methyl-3-((1-(7-methylbenzothiazole-2-yl)-1-methyl) ethyl)-5-phenyl-4H-1,3-oxazine-4-ketone, 3-((1-(4-fluoro benzothiazole-2-yl)-1-methyl) ethyl)-2,3-dihydro-6-methyl-5-phenyl-4H-1,3-oxazine-4-ketone, or 3-((1-(7,7-dichlorobenzothiazole-2-yl)-and the 1-methyl) ethyl)-2,3-dihydro-6-methyl-5-phenyl-4H-1,3-oxazine-4-ketone.
Formula (I) compound for example can prepare according to the method for following reaction (A) representative.(A)
R in above-mentioned
1, R
2And R
3As above limit, and R
8And R
9Be respectively alkyl.
Reaction (A) is normally carried out in the presence of solvent.Solvent can be, for example, and aromatic hydrocarbon such as benzene, toluene, dimethylbenzene or chlorinated benzene; Ring-type or non-annularity aliphatic hydrocarbon such as tetracol phenixin, chloroform, methylene dichloride, ethylene dichloride, trichloroethane, hexane or hexanaphthene, ether such as diox or tetrahydrofuran (THF); Ester such as methyl acetate or ethyl acetate; Or non-proton polarity is transmitted solvent such as dimethyl formamide, methyl-sulphoxide, thiotetrole sulfone (sulfolane), N,N-DIMETHYLACETAMIDE, N-Methyl pyrrolidone or pyridine.
Reaction (A) is carried out under heating, and temperature of reaction is generally 30 to 300 ℃, is preferably 50 to 200 ℃.Reaction times is generally 0.01 to 100 hour, is preferably 0.01 to 20 hour.
Formula (II) compound is a known compound, and can according to, for example at Japanese unexamined patent publication number 89485/1992 and 172485/1984, Chem.Pharm.Bull, Vol.31, No.6,1896-1901 (1 983), and ditto, Vol, 32, No.10, the method for being delivered among the 3848-3856 (1984) preparation.
Formula (III) compound for example can prepare by the method shown in the following reaction (B).In some example, formula (III) compound can equilibrium state trimeric with it and is existed.(B)
In following formula, R
3As above limit, M is sodium atom or potassium atom, and X is a chlorine, bromine or iodine, and condition is formula R
3R among the-CN
3Do not comprise by bromine atoms or the former group that replaces of iodine.
In the above-mentioned reaction formula (B), formula (VII) compound can be by preparing as the method for following reaction (C) to (F) representative.(C) work as R
3Be commutable
(D) work as R
3Be commutable
(E) work as R
3Be commutable
(F) work as R
3Be commutable
, D is-N (R
2)-, be R wherein
4When being alkyl:
Arrive in the formula of (F) D, X and R in reaction (C)
4The last qualification, R
5It is hydrogen atom; Halogen atom; The alkyl that can be replaced by halogen atom; The alkoxyl group that can be replaced by halogen atom; Can by halogen atom replace alkylthio; The alkyl sulphonyl that can be replaced by halogen atom; Can be by the aryl of halogen atom or haloalkyl replacement; By halogen atom or haloalkyl replace heteroaryl; By the aryloxy that halogen atom or haloalkyl replaced, or by the assorted fragrant oxygen worker that halogen atom or haloalkyl replaced, be chlorine atom or bromine atoms at Y, n is the integer of 1-4, and l is 1 to 3 integer.When n or e are 2 integer or bigger integer, R
5Major part can be identical or different.NBs represents N-bromosuccinimide, and NCS represents N-chlorosuccinimide.
In the above-mentioned reaction (B), formula (VI) compound can be according to reaction (G) or (H) the method preparation of representative, and reaching formula (V-1) compound can be by the method preparation of reaction (I) representative.Further, formula (IV) compound can be by the method preparation of reaction (J) representative.(G) work as R
3Be commutable
(H) work as R
3Be commutable
And D is-N (CH
3)-:
(J)
At reaction formula (G), in the formula (H) and (I), D, R
5, X and n as above limit.In the formula of reaction (J), R
3, M, X, NBS and NCS as above limit, and Hal is a halogen atom, and R
6Be halogen atom, alkoxyl group, benzyloxy or phenoxy group.
Further, in above-mentioned reaction (C) with (G), in the compound of formula (VIII), wherein D is a sulphur atom, can be according to the method preparation of reaction (K) representative.(K)
In reaction (K) formula, Hal, R
5As above limit with n, and R
7Be hydrogen atom, chlorine atom, phenyl ,-OH ,-NH
2Or
Used solvent or the inert solvent of above-mentioned reaction (B) to (K) can be selected from aromatic hydrocarbon such as benzene than appropriate ones, toluene, dimethylbenzene and chlorobenzene; Ring-type and non-annularity aliphatic hydrocarbon such as chloroform, tetracol phenixin, methylene dichloride, dichloro hexane, trichloroethane, hexane and hexanaphthene, ether such as ether ， diox and tetrahydrofuran (THF); Nitrile such as acetonitrile, propionitrile and vinyl cyanide; Ester such as methyl acetate and ethyl acetate; Non-proton polarity is transmitted solvent such as methyl-sulphoxide, thiotetrole sulfone, N,N-DIMETHYLACETAMIDE, dimethyl formamide, N-Methyl pyrrolidone and pyridine; Ketone such as acetone and methylethylketone; Pure as methyl alcohol, the ethanol and the trimethyl carbinol; Organic and mineral acid such as acetic acid, formic acid and hydrochloric acid; And water.The alkali that is suitable for can be selected from carbonate such as salt of wormwood and yellow soda ash; Supercarbonate such as saleratus and sodium bicarbonate; Metal hydroxides such as potassium hydroxide and sodium hydroxide; Tertiary amine such as triethylamine; With pyridines and pyridine and 4-Dimethylamino pyridine.Rare gas element can suitably be selected from gas such as argon, helium and nitrogen.Mention dewatering agent and can give an example as N N '-dicyclohexyl carbodiimide.Catalyzer can give an example as 2,2 '-Diisopropyl azodicarboxylate, metachloroperbenzoic acid or illumination.Acid can be formic acid, hydrochloric acid, Hydrogen bromide or sulfuric acid.Alkali can be for example potassium hydroxide, sodium hydroxide or sodium Metal 99.5.It is example that superoxide can be lifted hydrogen peroxide.
In the reaction (K) reductive agent of nitro can give an example as, tin chloride, sodium sulphite (Na
2S, Na
2S
2, Na
2Sx), Sodium sulfhydrate (NaSH), V-Brite B (Na
2S
2O
4), ammonium sulfide ((NH
4)
2S) or the reductive agent described in hydrazine and the above-mentioned reaction process.If the applied catalysis reduction method, platinum dioxide then, Raney nickel, palladium-carbon, ruthenium, iron, copper or hydrogen-transfer catalyst and the available reactant can be exemplified as hydrogen, ammonium fumarate, alcohol, tetrahydrobenzene, fumaric acid, fumaric acid triethylamine salt or ammonium chloride.
Show by test implementation example shown in hereinafter, when chemical combination of the present invention is used as the active constituent of herbicidal composition, shown fabulous herbicidal effect.Especially, it can prevent and treat the injurious weed that grows in the rice terrace, low and nontoxic as selectively preventing and treating gramineous weeds barnyard grass (Echinochloscrusgalli) consumption to rice, and compare with corresponding weedicide, the weeding long-lasting is more excellent, thereby can obtain persistent weeding activity in a long time.And has the mixed or compatibility of components of herbicidal effect when using when it and hereinafter described other, selectively be used for preventing and treating gramineous grass other weeds in addition and comprise Cyperus weeds such as Japanese nutgrass flatsedge (Scirpus juncoides), water rhizoma sparganic (Cyperus serotinus, Herba Cyperi Difformis (rice galingale herb) (Cyperus difformis), Herba Eleocharitis acicularis (Eleocha ris acicularis), and waterchestnut (Eleocharis kuroguwai), Waterplantain weeds such as Sagittaria pygmaea (Sagittariapygmaea), arrowhead (Sagittaria trifolia), with wear leaf rhizoma alismatis (Alismacnaliculatum), pontede riaceae such as first crow tongue grass (Monochoriavaginalis), scrophulariaceae weeds such as Procumbent Falsepimpernel (Lindernia pyxidaria), with Lythraceae weeds such as Herba Clinopodii Polycephali (Rotala indica), permanently effective and nontoxic to rice.Thereby this composition can be used as Herbicidal composition for paddy fields.
The herbicidal composition that comprises The compounds of this invention can be applicable to various place, and rice terrace still not also comprises dry land and non-agricultural as forest, farm road, square and plant area.And the application's method is suitable for soil and the control of electing property of leaf is handled.
The compounds of this invention mixes with various agriculture auxiliarys usually and is mixed with various formulations such as granule, water-dispersible granular material agent, wettable powder, aqueous suspension, suspension oil solution, the aqueous solution, but emulsion concentrate, tablet or capsule.
This class agricultural auxiliary comprises solid carrier such as diatomite, white lime, lime carbonate, talcum, hard charcoal (Calucium Silicate powder), kaolin, bentonite, jeaklite, clay, and starch; Solvent such as water, toluene, dimethylbenzene, solvent naphthalene ， diox, acetone, isophorone, methyl iso-butyl ketone (MIBK), chlorobenzene, hexanaphthene, methyl-sulphoxide, dimethyl acid amides, N-methyl-2-pyrrolidone and ethanol; Dispersion agent or tensio-active agent are such as sodium alkyl sulfate, sodium alkyl benzene sulfonate, sodium lignosulfonate, the polyoxyethylene alkylaryl ether sulfuric ester, the polyoxyethylene glycol alkyl oxide, polyoxyethylene lauryl ether, polyoxyethylene alkyl aryl ether, polyoxyethylene fatty acid ester, and Vykamol Sorbitol 8B; Plant and animal oil is such as sweet oil, baobab oil, Viscotrol C, plam oil, tea oil, Oleum Cocois, sesame oil, Semen Maydis oil, Rice pollard oil, peanut oil, Oleum Gossypii semen, soybean oil, rapeseed oil, Semen Lini oil, tung oil and whiteruss; Relevant auxiliary with other such as weighting agent, thickening material, antisettling agent, antifreezing agent, toxic agents falls in dispersion stabilizer, and anti-mycotic agent.
Herein, The compounds of this invention is generally 0.1: 99.9 to 90: 10 to the weight ratio of agriculture auxiliary, is preferably 0.2: 99.8 to 80: 20.
The dosage of herbicidal composition of the present invention is unrestricted usually, because it can be according to weather condition, and edaphic condition, institute's ingredients type classification, the kind of required control grass is used season etc. and is changed.But the common consumption of The compounds of this invention is 0.1 to 40g/a, is preferably 0.5 to 20g/a.
Herbicidal composition of the present invention can mix or in conjunction with other agricultural chemicalses, fertilizer or fall toxic agent.And can demonstrate better effect or activity.For example, mixed or composite one or more other weeding activity components are as mentioned below when The compounds of this invention, can obtain synergism.
The ratio of chemical combination of the present invention and these other weeding activity is unrestricted usually, because it can be according to weather condition, and edaphic condition, the formulation type is used season, application mode etc. and changing.But other herbicidal activity components of at least a this class are in every part of weight of The compounds of this invention, and general content is preferably 0.02 to 60 part of weight 0.01 to 100 part of weight.All the total amount of active constituent is generally 0.2 to 100g/a, is preferably 0.5 to 50g/a.
Classify the concrete kind embodiment composite down as with other weedicide components.
Diphenyl ether compound as:
2,4,6-trichlorophenyl-4-nitrophenyl ether (popular name: chlornitrofen),
(5-(2,4 dichloro benzene oxygen base)-2-nitroanisole (and popular name: Chlomethoxyfen) and
5-(2,4 dichloro benzene oxygen base)-2-nitrobenzoic acid methyl esters (popular name: bifenox),
Heterogeneous ring compound such as the 5-tertiary butyl-3-(2,4-two chloro-5-o-phenyl-isopropyls)-1,3,4-oxadiazole-2 (3H)-ketone (popular name: oxadiazon),
3-(5-(cyclopentyloxy-4-chloro-2-fluorine) phenyl)-5-isopropylidene-1,3-oxazolidine-2, the 4-diketone the 17th Japanese Pesticide Science can on the paper delivered, p.48 (1992) described compound),
2-difluoromethyl-4-(2-methyl-propyl)-6-(trifluoromethyl) 3,5-pyridine thioic acid sulfoacid S, the S-dimethyl ester (popular name: dithiopyr),
Outward-1-methyl-4-(1-first and second bases)-2-((2-tolyl) methoxy)-7-Evil dicyclo (2,2.1) heptane (popular name: cinmethylin),
3,7-dichloroquinoline-8-carboxylic acid (popular name: quinclorac),
1-(diethylin formyl radical)-3-(2,4,6-Three methyl Benzene alkylsulfonyl-) 1,2,4-triazole (1991) Vol.36, fascicle I, the 30th time, the p.27 middle compound that discloses),
3-sec.-propyl-2,1,3-benzothiadiazine-4-ketone-2, the 2-dioxide (popular name: bentazone) and sodium salt,
Ethylsulfonic acid 2,3-dihydro-3,3-dimethyl benzofuran-5-base ester (popular name: benfuresate), and 2-((4,6-dimethoxypyridin-2-yl) oxidation)-6-(1-(N-methoxyl group imines) ethyl) methyl benzenecarboxylate (compound that is disclosed among the open No.134073/1992 of Japanese unexamined patent)
N-(certain) acyl phenyl compound as
2-chloro-2 ', 6 '-diethyl-N-(the 2-third oxygen ethyl) monoacetylaniline (popular name: pretilachlor),
2-chloro-N-((3-methoxyl group-2-thiophene branch) methyl)-2 ' 6 '-N-dimythyl acetanilide (popular name: thenylchlor),
2 ', 3 '-two chloro-4-N-oxyethyl group methoxy base benzanilides (popular name: etobenzanide),
2-((benzothiazole-2-yl) oxo)-N-methyl acetanilide N (popular name: mefenacet),
2-(2-naphthyloxy) propionanilide (popular name: naproanilide) and
2-(2,4-two chloro-3-methylphenoxy) propionanilide (popular name: grass is red),
Carbamate compounds as
N, N-diethyl thiocarbamate-S-(4-chlorobenzene ester) (popular name: thiobencarb),
Hexahydroxy--1H-azatropylidene 1-carboxylic vulcanize sour S-ethyl ester (popular name: Hydram),
S-(1-methyl isophthalic acid-styroyl) piperidines-1-thiol manthanoate (popular name: Youkebai (dimepiperate),
N-(1, the 2-dimethylpropyl)-N-ethylenebis dithiocarbamate carboxylamine-S-benzyl ester (popular name: esprocarb), and
N-(6-methoxyl group-2-pyridyl)-N-methyl thiocarbamate O-(3-trimethylphenylmethane ester) (popular name: pyributicarb),
The benzene siloxane compound as
2-(4-(4-cyano group-2-fluorobenzene oxygen) benzene oxygen)-propionic acid (R)-positive butyl ester
Compound shown in the open No.65201/993 of Japanese unexamined patent),
Solsonylurea compounds as
2-((((((4,6 dimethoxypyridins-2-yl) ammonia) carbonyl) amino) alkylsulfonyl) methyl) methyl benzoate (popular name: methyl benzyl ethyl methyl),
N-(((4,6-SDM-2-yl) ammonia) carbonyl)-4-ethoxycarbonyl-1-methyl-5-pyrazoles sulphonamide (popular name: pyrazosulfuron),
1-(2-chlorine imidazoles (1.2-a) pyridin-3-yl alkylsulfonyl)-3-(4,6-dimethoxy-2-pyridyl) urea (popular name: imazosulfuron),
3-(4,6-dimethoxy-1,3,5-triazines-2-yl)-1-(2-(2-methoxy ethoxy) benzenesulfonyl) urea (popular name: cinosulfuron),
5-(2,2-two fluoro-2-fluorine ethoxies)-N-(((4,6-dimethoxy imidazoles-2-yl) ammonia) carbonyl)-3-methyl-4-isothiazole sulfonic acid ammonia
Compound shown in the open No.190887/1988 of Japanese unexamined patent),
N-(((4,6-dimethoxy-2-miaow pyridine base) amino) carbonyl)-1-methyl-4-(2-methyl-2H-tetrazolium-5-yl)-1H-pyrazoles-5-sulphonyl ammonia (popular name: azimsulfuron) and
1-((2-(cyclopropyl carbonyl) phenyl) sulfamyl)-3-(4,6-dimethoxy-2-miaow pyridine base) urea
Compound shown in the open No.224567/1992 of Japanese unexamined),
Pyrazole compound as
2-(4-(2,4 dichloro benzene formyl radical)-1,3-dimethyl pyrazole-5-base oxo) phenyl methyl ketone (popular name: pyrazoxyfen),
4-(2,4 dichloro benzene formyl radical)-1,3-dimethyl-5-pyrazolyl-right-tosylate (popular name: pyrazolate) and
2-(4-(2, between 4-two chloro--toluyl)-1,3-two fomepizoles-5-base oxo-4 '-methyl acetanilide (popular name: benzofenap),
Benzyl ammoniate such as 2-bromo-N-(α, alpha, alpha-dimethyl benzyl)-3,3-diformazan fourth ammonia (popular name: bromobutide),
Carbamide compound as
1-(α, α-Er Jiajibianji)-3-(p-methylphenyl) urea (popular name: daimuron) and
1-(2-benzyl chloride base)-3-(α, alpha, alpha-dimethyl benzyl) urea (popular name: cumyluron),
Triaizine compounds as
2-methyl sulfo--4, two (first the ammonia)-S-triazines of 6-(popular name: simetryn) and
2-methyl sulfo--4-second ammonia 6-(1 ', 2-diethyl third ammonia)-S-triazine (popular name: diformazan third second is striven),
The benzene oxygen compound as
2,4 dichlorophenoxyacetic acid and its salt and ester (popular name: 2,4-drips),
4-(4-chloro-neighbour-toluene oxygen) propionic acid and salt thereof and ester (popular name: 2-first-4-chloro-butyric acid and
4-chloro-2-methylenedioxy phenoxy thioacetic acid S-ethyl ester (popular name: diformazan chloro-thio-ethyl) and
Other compounds as
2-(2-(3-chloro-phenyl-)-2,3-epoxypropyl)-2-ethylidine 1,3-diketone (compound that is disclosed among the open No.304043/1990 of Japanese unexamined patent).
The present invention will describe in more detail by embodiment.But it must be understood that also the present invention is not limited to these specific embodiments.The preparation embodiment of The compounds of this invention is described at first earlier.Preparation embodiment 1
3-((1-(benzothiazole-2-yl)-1-methyl) ethyl)-2,3-dihydro-6-methyl-5-phenyl-4H-1,3-oxazine-4-ketone
(hereinafter the compound N of indication o.1)
(1) the 5.1g sodium hydride is joined in the 200ml dry tetrahydrofuran, then mixture is cooled to-10 to 0 ℃ (with sodium hydride suspension, the 50ml tetrahydrofuran solution that will contain 10g benzothiazole-2-base acetonitrile then is added dropwise to wherein between 0 to 10 ℃, and miscellany was stirred 1 hour down at 70 ℃.Then, be cooled to-10 to 0 ℃ of temperature.Under 10 ℃ of temperature, be added dropwise to the 17.26g methyl iodide again-10, with miscellany 2 nights of stirring reaction at room temperature.
After reaction is finished, add reaction product in the frozen water and use ethyl acetate extraction.Then, wash extraction liquid with sodium chloride solution, and through anhydrous sodium sulfate drying and filtration.The filtrate decompression distillation that obtains is desolvated, and resistates is through column chromatography purification (developping agent: toluene), obtain 10.7g, fusing point is 2-[4-morpholinodithio-2-yl of 44 to 46 ℃)-2-methyl propionitrile.
(2) 10.25g2-(benzothiazole-2-yl)-2-methyl propionitrile is dissolved in 70ml and (in the trimethyl carbinol, and adds 5.7g potassium hydroxide powder.Miscellany was 80 ℃ of following stirring reactions 1 hour.
After reaction finished, the reaction product cool to room temperature was poured in the water, uses ethyl acetate extraction again.Then, with chloride soln washing extraction liquid and through anhydrous sodium sulfate drying.Underpressure distillation is desolvated, and sedimentary crystallization is washed with ether/hexane=1/1 miscellany, and drying under reduced pressure obtains 2-(benzothiazole-2-yl)-2-methyl propanamide that 5.09g has 133 to 134 ℃ (fusing point).
(3) with the 2.21g dissolution of sodium hydroxide in 13ml water and the aqueous solution, and be cooled to-10 to 0 ℃ of temperature, drip 469 μ l bromines then.Miscellany was stirred 30 minutes.Then, add 2g2-(benzothiazole-2-yl)-2-methyl propanamide, miscellany stirring reaction under-10 to 0 ℃ of temperature then, and at room temperature further stir and spend the night.
After reaction is finished, under-10 to 20 ℃ of temperature, hydrochloric acid is added dropwise in the reaction product, the pH value is adjusted to 1.Then, toluene is added wherein, use dilute hydrochloric acid (10%) to strip then.Between-10 to 20 ℃ of temperature, dropping ammonia is to regulate pH to 14 in the water layer of gained.Miscellany washs with dichloromethane extraction and with sodium chloride aqueous solution.Then,, again solvent is under reduced pressure steamed, obtain 870mg oily 1-(benzothiazole-2-yl)-1-methyl ethyl-amine through anhydrous sodium sulfate drying.
(4) 1.02g that will obtain by the same procedure of above-mentioned steps (3)
1-(benzothiazole-2-yl)-1-methyl ethyl-amine and 195mg paraformaldehyde are dissolved in the 10ml dry toluene, then miscellany was reacted 40 minutes under 90 to 100 ℃ of temperature, and then further under the azeotropic dehydration condition back flow reaction 7 hours to be contained the solution of (1-(benzothiazole-2-yl)-1-methyl-N-methylene radical) ethamine.
(5), and add 1.4g 2,2,6-trimethylammonium-5-phenyl 4H-1,3-dioxy-4-ketone with gained solution cooling in the above-mentioned steps (4).Miscellany back flow reaction 16 hours, cool to room temperature again.Boil off solvent, resistates is analysed purification (developping agent methylene dichloride) through post, obtains 210mg white crystals shape, has the required product of 166 to 168 ℃ of fusing points.Preparation embodiment 2
3-((1-(5-chloro thiophene)-1-methyl) ethyl)-2,3-dihydro-6-methyl-5-phenyl-4H-1, the preparation of 3-oxazine-4-ketone (hereinafter the indication compound N is o.6)
(1) with the 64g2-chlorothiophene, 115ml35% formalin and 11.48g zinc chloride are dissolved in the 150ml ether, then solution are cooled to-5 ℃.Then, feed hydrogen chloride gas, and be not higher than under 10 ℃ the temperature reaction 2 hours.
Reaction is poured reaction product in the frozen water into, and is used extracted with diethyl ether after finishing.Then, it through anhydrous sodium sulfate drying, is or else steamed ether being higher than under 40 ℃ of temperature, obtain the brown 2-chloro-of 73.8g oily 5-chloromethyl thiophene.
(2) with the 2-chloro-5-chloromethyl thiophene of 73.8g above-mentioned steps (1) gained, with the 39.5g sodium hydride, 100ml acetone and 100ml water are mixed, then, with mixture about 60 ℃ of following stirring reactions 5.5 hours.
Reaction boils off acetone, and uses the dichloromethane extraction reaction product after finishing.Extraction liquid washs with sodium chloride aqueous solution.Through anhydrous sodium sulfate drying, boil off solvent more then.Resistates is through column chromatography purification (developping agent: toluene/methylene dichloride=-8/2), obtain 11.37g (5-chlorothiophene-2-yl) acetonitrile.
(3) 11.37g (5-chlorothiophene-2-yl) acetonitrile that makes in the above-mentioned steps (2) is dissolved in the 300ml dry tetrahydrofuran, this solution is cooled to-70 ℃ under inert gas atmosphere.Be not higher than the hexane solution that drips the 104ml n-Butyl Lithium under-60 ℃ of temperature then, and miscellany was being stirred 1.5 hours under-70 ℃ of temperature approximately.Be not higher than dropping 12.3ml methyl iodide under-55 ℃ of temperature then, and the miscellany placement is being spent the night.
Reaction is poured reaction product in the frozen water into after finishing, and ethyl acetate extraction.Extraction liquid washs with sodium chloride aqueous solution.Then through anhydrous sodium sulfate drying, pressure reducing and steaming solvent again.Resistates is through column chromatography purification (developping agent; Toluene), obtain the brown 2-of 11.2g oily (5-chlorothiophene-2-yl)-2-methyl propionitrile.
(4) 12.3g 2-(5-chlorothiophene-2-yl)-2-methyl propionitrile and the 7.43g potassium hydroxide powder that makes in the above-mentioned steps (3) is dissolved in the 50ml trimethyl carbinol, and reacted 2 hours down at 80 ℃.
After reaction finishes, with the reaction product cool to room temperature and use ethyl acetate extraction.Extraction liquid with the sodium chloride aqueous solution washing repeatedly.Through anhydrous sodium sulfate drying, boil off solvent more then, resistates is purified through column chromatography, and (developping agent: dichloromethane/ethyl acetate=8/2), make 8.95g 2-(5-chlorothiophene-2 base)-2-methyl propanamide, be the light brown crystallization, fusing point is 90-93 ℃.
(5) 3g2-that will make from above-mentioned steps (4) (5-chlorothiophene-2-yl)-2-methyl propanamide joins in advance and is reacted in the hypobromous acid that makes down at 0 ℃ by 30ml3N sodium hydroxide and 2.46g bromine, and miscellany was reacted 6 hours under 0 to-5 ℃ of temperature.
Reaction is adjusted to reaction product pH1 and uses toluene wash with hydrochloric acid after finishing.In water layer, add ammoniacal liquor, make it alkalize, use dichloromethane extraction then.Extraction liquid washs with sodium chloride aqueous solution.Then through anhydrous sodium sulfate drying.The pressure reducing and steaming solvent makes 1.6g oily 1-(5-chlorothiophene-2-yl)-1-methyl ethyl-amine.
(6) 630ng1-that will make from above-mentioned steps (5) (5-chlorothiophene-2-yl)-1-methyl ethyl-amine and 132mg paraformaldehyde are dissolved in the 200ml dry toluene, reacted 40 minutes down at 90 to 100 ℃ then, back flow reaction 7 hours under the azeotropic dehydration condition makes the solution that contains (1-(5-chlorothiophene-2-yl)-1-methyl-N-methylene radical) ethamine again.
The solution cooling that (7) will make from above-mentioned steps (6) adds 957mg2 then, and 2,6-trimethylammonium-5-phenyl-4H-1,3-dioxy-4-ketone.With miscellany back flow reaction 18 hours.
After reaction finished, the reaction product cool to room temperature boiled off solvent then, and resistates is through column chromatography purification (developping agent: toluene/methylene dichloride=1/1), obtain the required product of 499mg, be transparent oily mater.
NMR:(60 MHz, δ CDCl | 3) 1.92 (9H, s), 5.1 (2H, s), 6.75 (2H, s), 7.13-7.40 (5H, m) preparation embodiment 3
3-((1-(4-chloro benzothiazole-2-yl)-1-methyl) ethyl)-2,3-dihydro-6-methyl-5-phenyl-4H-1, the preparation of 3-oxazine-4-ketone (compound N hereinafter is o.48)
(1) 9.0g 4-chloro benzothiazole is dissolved in the 100ml ethanol, adds the 100ml hydrazine hydrate again, miscellany back flow reaction 16 hours.
After reaction finished, the pressure reducing and steaming solvent obtained 8.0g oily 2-amino-3-chlorothio-phenol
(2) 8.0g 2-amino-3-chlorothio-phenol is dissolved in the 15ml ethanol.In this solution, add 20ml vinegar phenol then, add the 4.0g propane dinitrile again.Miscellany at room temperature reacted 3 hours.
After reaction finishes, reaction product is poured in the water, and filtered the collecting precipitation crystallization, water thoroughly washs then, and drying makes 8.0g (4-chloro thiophene-2-yl) acetonitrile, and fusing point is 119-121 ℃.
(3) with 8.0g (4-chloro benzothiazole-2-yl) acetonitrile, be dissolved in the 100ml tetrahydrofuran (THF), in this solution, add the 3.4g60% sodium hydride gradually, drip the 12g methyl-iodide then.Miscellany at room temperature reacted 16 hours.
After reaction finishes, pour into reaction product in the water and use ethyl acetate extraction.Extraction liquid is through anhydrous sodium sulfate drying.Then, pressure reducing and steaming solvent.The gained resistates is purified through column chromatography, and (developping agent: ethyl acetate/hexane=1/3), make 6.5g2-(4-chloro benzothiazole-2-yl)-2-methyl propionitrile, fusing point is 95 to 97 ℃.
(4) 6.5g2-(4-chloro thiophene-2-yl)-2-methyl propionitrile is dissolved in the 80ml formic acid, in this solution, under 40-50 ℃ of temperature, feeds hydrogen chloride gas, reacted again 5 hours.
After reaction finishes, pour into reaction mixture in the water and use ethyl acetate extraction.Extraction liquid is through colourless dried over sodium sulfate, then the pressure reducing and steaming solvent.(developping agent: ethyl acetate/hexane=1/1), obtain 6.5g2-(4-chloro benzothiazole-2-yl)-2-methyl propanamide, fusing point is 92 to 94 ℃ to the gained resistates through column chromatography.
(5) under-10-0 ℃ temperature, the 1.2ml bromine joined gradually contain the 4.7g sodium hydroxide solution in the solution of 60ml water, miscellany reaction 30 minutes.In the gained reaction soln, add 6.0g2-(4-chloro benzothiazole-2-yl)-2-methyl propanamide, then miscellany was at room temperature reacted 1 hour, further reacted 1 hour down at 80 ℃ again.
Reaction is poured reaction product in the water into after finishing, and uses dichloromethane extraction then.Extraction liquid is through anhydrous sodium sulfate drying.The pressure reducing and steaming solvent obtains 3.6g oily 1-(4-chloro benzothiazole-2-yl)-1-methyl ethyl-amine then.
(6) by the same procedure of step (4) and (5) among the preparation embodiment 1, can make required product.Preparation embodiment 4
2,3-dihydro-3-((1-(6-methoxy benzothiazole-2-yl)-1-methyl) ethyl)-6-methyl-5-phenyl-4H-1, the preparation of 3-oxazine-4-ketone (hereinafter the indication compound N is o.9)
(1) 3g2-cyano group-6-methoxyl group benzo thiazole is dissolved in the 100ml toluene, adds the diethyl ether solution 16ml that contains the 3mol/l methylmagnesium-bromide then.With miscellany back flow reaction 1 day.Then, the reaction mixture temperature drops to room temperature, adds the 10ml dehydrated alcohol, and miscellany further reacts.Filter out precipitated crystal.
Then, boil off the solvent in the filtrate, in resistates, add entry, use the ethyl acetate extraction miscellany again.Extraction liquid is through anhydrous sodium sulfate drying, the pressure reducing and steaming solvent.The gained resistates is with the column chromatography (developping agent: acetate-ethyl ester) obtain 0.5g oily 1-(6-methoxyl group benzo thiazol-2-yl)-1-methyl ethyl-amine of purifying.
(2) 1g1-(6-methoxyl group benzo thiazol-2-yl)-1-thyl methyl amine and the 135mg paraformaldehyde with gained in the above-mentioned steps (1) is dissolved in the 10ml toluene, and reflux solution 1 hour.Then, carry out 7 hours azeotropic dehydration reaction, contained the solution of (1-(6-methoxy thionaphthene-2-yl)-1-methyl-N-methylene radical) ethamine.
(3) solution of cooling above-mentioned steps (2) gained adds 980mg2 then therein, and 2,6-trimethylammonium 5-phenyl-4H-1,3-dihydro-4-ketone.The back flow reaction miscellany spends the night.
After reaction finishes, with the reaction mixture cool to room temperature.Boil off solvent then, resistates is purified through column chromatography, and (developping agent: methylene dichloride), obtain the required product of 500mg, be white crystals, fusing point is 160-162 ℃.Preparation embodiment 5
2,3-dihydro-6-methyl-3-((1-methyl isophthalic acid-(2-pyridyl)) ethyl 3-((1-(7-ethyl-5-phenyl-4H-1, the preparation of 3-oxazine-4-ketone (compound N hereinafter is o.8)
(1) 25g2-pyridyl acetonitrile is dissolved in the 400ml dry tetrahydrofuran, in inert gas atmosphere, solution is cooled to-10 ℃.Then, the hexane solution (1.66M) of 284mg n-Butyl Lithium is added drop-wise to wherein not being higher than under 7 ℃ of temperature, and miscellany was at room temperature reacted 1.5 hours.Reaction product is cooled to-5 ℃.Be not higher than then under-5 ℃ of temperature, dripping the 29ml methyl iodide therein, miscellany is at room temperature being reacted spend the night then.
After reaction finishes, add reaction product in the frozen water gradually and wash with the acetate acetic acid extraction and with sodium chloride aqueous solution.Then through anhydrous sodium sulfate drying.The pressure reducing and steaming solvent, resistates is through column chromatography purification (developping agent: dichloromethane/ethyl acetate=8/2), obtain 18.77g oily xanchromatic 2-methyl-2-(2-pyridyl) propionitrile.
(2) 2-methyl-2-that 19.17g is obtained from above-mentioned steps (1) (2-pyridyl) propionitrile is added drop-wise in the 30ml vitriol oil under not being higher than 8 ℃ of temperature.Miscellany at room temperature reacts to spend the night to be poured in the water then.Reaction product alkalizes with ammoniacal liquor, uses ethyl acetate extraction then.Extraction liquid washs with sodium chloride solution.Then through anhydrous sodium sulfate drying, pressure reducing and steaming solvent again, resistates is recrystallization from toluene, obtains 5.57g2-methyl-2-(2-pyridyl) propionic acid amide (fusing point: 99-100 ℃), is white crystals.
(3) 37ml3N sodium hydroxide is cooled to-10 ℃, splashes into the 2.93g bromine not being higher than under 0 ℃ of temperature then.Miscellany was stirred 30 minutes not being higher than under 0 ℃ the temperature.Add 3g2-methyl-2-(2-pyridyl) propionic acid amide that makes from above-mentioned steps (2) then therein.Reaction mixture is after 8 hours under 0 ℃ of temperature not being higher than, and stirring is spent the night.Refluxed again 3 hours, and cooled off reaction product then.Use dichloromethane extraction, and extraction liquid washs with sodium chloride aqueous solution.Through anhydrous sodium sulfate drying, the pressure reducing and steaming solvent obtains the brown 1-methyl isophthalic acid of 1.15g oily-(2-pyridyl) ethamine then again.
(4) the 1-methyl isophthalic acid that 842mg above-mentioned steps (3) is made-(2-pyridyl) ethamine and 186mg paraformaldehyde are dissolved in the 20ml dry benzene, then solution was heated 30 minutes down at 80 to 90 ℃, the azeotropic dehydration that refluxes again reaction 7 hours obtains containing 1-methyl-N-methylene radical-1-(2-pyridyl) ethylamine solution.
(5) cooling above-mentioned steps (4) gained solution.Add 1.35g2 then, 2,6-trimethylammonium-5-phenyl-4H-1,3-dioxy-4-ketone was with miscellany back flow reaction 18 hours.
After reaction finishes, the cooling reaction product, the pressure reducing and steaming solvent, resistates obtains the required product of 676mg with column chromatography purification (developping agent, dichloromethane/ethyl acetate=1/1), is the yellow oily material.
NMR:(60MHz, δ: at CDCl
3In) 1.77 (6H, s), 1.87 (3H, s), 5.33 (2H, s), 6.83-7.73 (9H, m), 8.43-8.60 (1H, m) preparation embodiment 6
3-((1-(7-chloro benzothiazole-2-yl)-1-methyl) ethyl)-2,3-dihydro-6-first-5-phenyl-4H-1, the preparation of 3-oxazine-4-ketone (compound N hereinafter is o.3)
(1) 25.3g sodium is added in the 500ml dehydrated alcohol gradually, then, the cooling miscellany feeds hydrogen sulfide, obtains sodium sulfhydrate solution.Then, add 192g2 therein gradually, the 3-dichloronitrobenzene, and miscellany limit coronite is warmed up to 80 ℃.Cool off reaction product again and pour in the water.Then with toluene wash water layer and cooling.Be not higher than under 5 ℃ of temperature, with hcl acidifying it, wash the gained crystallization with water.These crystallizations are dissolved in the methylene dichloride and with sodium chloride aqueous solution wash.Through anhydrous sodium sulfate drying, the pressure reducing and steaming solvent obtains 63g2-chloro-6-nitro thiophenol, is yellow crystal then, and fusing point is 55 to 58 ℃.
(2) 30g above-mentioned steps (1) gained 2-chloro-6-nitro thiophenol is dissolved in the 700ml acetic acid, then solution is heated to 70 ℃ in rare gas element.Then 72.3g zinc is progressively added wherein, and under 80 to 100 ℃, reacted 1 hour, cool off reaction product again, fed hydrogen sulfide 1 hour, and half is used for excess zinc being changed into zinc sulphide not being higher than under 35 ℃, in this solution, add the 31.3g propane dinitrile, miscellany at room temperature reacts and spends the night.
After reaction finishes, reaction product by diatomite filtration, is added entry then.Miscellany extracts with methyl chloride, and extraction liquid washes with water again through anhydrous sodium sulfate drying.Boil off solvent, resistates is purified through column chromatography, and (developping agent: methylene dichloride) obtain 16.3g7-chloro thiophene-2-base acetonitrile, be yellow crystal, molten point is 112-113 ℃.
(3) 16.3g above-mentioned steps (2) is made 7-chloro benzothiazole-2-base acetonitrile and be suspended in the 200ml dry tetrahydrofuran, under inert gas atmosphere, in suspension, drip 6.87g sodium hydride (60%).Miscellany 60 times reactions 1 hour, is cooled to-10 ℃ then.Not being higher than 10 ℃ of adding 11.7ml methyl iodide down, miscellany was at room temperature reacted 2 hours.
Reaction is poured reaction product in the frozen water into, and is used ethyl acetate extraction after finishing.Extraction liquid washs with sodium chloride aqueous solution, and through anhydrous sodium sulfate drying.Boil off solvent then, resistates is through column chromatography purification (developping agent: methylene dichloride), obtain 17.67g2-(7-chloro thiophene-2-yl)-2-methyl propionitrile, be brown crystallization (fusing point: 69-71 ℃).
(4) 2-that 17.67g is made from above-mentioned steps (3) (7-chloro benzothiazole-2-yl)-2-methyl propionitrile is dissolved in the 50ml formic acid, solution is heated to 60-70 ℃ then, feeds hydrogen chloride gas again, and reacts 4 hours.
After reaction finishes, the cooling reaction product is also poured in the water, the miscellany ethyl acetate extraction, extraction liquid washes with water, boil off solvent, and first water uses crystallization of toluene wash gained and drying under reduced pressure then, obtains 15.79g2-(7-chloro benzothiazole-2-yl)-2-methyl-propionic acid amide (fusing point: 139-141 ℃).
(5) with the 2.86g dissolution of sodium hydroxide in 20ml water, and cooling solution.Then the 6.69ml bromine is joined wherein not being higher than under 0 ℃ of temperature, miscellany stirred 30 minutes, in this solution, added above-mentioned steps (3) gained 2-(7-chloro thiophene-2 base)-2-methyl propanamide, and miscellany is 70 ℃ of reactions 2 hours down.
After reaction finishes, with the reaction mixture cool to room temperature and use dichloromethane extraction.Extraction liquid washes with water uses anhydrous sodium sulfate drying again, boils off solvent, and resistates is through column chromatography purification (developping agent: dichloromethane/ethyl acetate=6/4), obtain (1-(7-chloro benzothiazole-2-yl)-1-methyl) ethamine of the semi-solid attitude of 2.3g.
(6) 1-(7-chloro benzothiazole-2-yl)-1-methyl ethyl-amine and the 151mg paraformaldehyde with 930mg above-mentioned steps (5) gained is dissolved in the 20ml dry toluene, and solution was reacted 30 minutes under 90-100 ℃ of temperature.Further, reflux and to carry out azeotropic dehydration reaction 7 hours, make contain (1-7-chloro benzothiazole-2-yl)-1-methyl-N-methylene radical) solution of ethamine.
(7) in above-mentioned steps (6), in the gained solution, add 896mg 2,2,6-trimethylammonium-5-phenyl-4H-1,3-dioxy-4-ketone reacts miscellany 18 hours down at 120 ℃ then.
After reaction finished, the pressure reducing and steaming solvent then, was made column chromatography purification secondary (developping agent: methylene dichloride), obtain the required product of 270mg, be brown oil matter with resistates.
NMR:(60MHz, δ: at CDCl
3In) 1.90 (3H, s), 1.93 (6H, s), 5.40 (2H, s), 7.17-7.99 (8H, m).
Further, above-mentioned oily mater is purified three times by identical column chromatogram chromatography, obtain the required product of 110mg, be white crystals, fusing point is 115.5 to 118 ℃.
Believable is that above-mentioned (III) is new compound to (VII) intermediate, and following tabulation 1-1 has listed the representative embodiment of these intermediates to 1-5.
Table 1-1
| Intermediate No. | R 3 |
| 1 | Thiophene-2-base |
| 2 | 5-chlorothiophene-2-base |
| 3 | Thiene-3-yl- |
| 4 | Thionaphthene-2-base |
| 5 | Thionaphthene-3-base |
| 6 | Cumarone-2-base |
| 7 | Benzothiazole-2-base |
| 8 | 4-chloro-benzothiazole-2-base |
| 9 | 4-methylbenzothiazole-2-base |
| 10 | 4-methoxyl group benzo thiazol-2-yl |
| 11 | 6-methoxyl group benzo thiazol-2-yl |
| 12 | 5-chloro benzothiazole-2-base |
| 13 | 6-chloro benzothiazole-2-base |
| 14 | 5-fluoro benzothiazole-2-base |
| 15 | 5-(trifluoromethyl) benzothiazole-2-base |
| 16 | Benzoxazole-2-base |
| 17 | 5-Lv benzoxazole-2-base |
| 18 | 6-Jia base benzoxazole-2-base |
| 19 | 1-tolimidazole-2-base |
| 20 | 1-normal-butyl benzo imidazoles-2-base |
| 21 | 5-ammonia-1-tolimidazole-2-base |
| 22 | 6-fluoro benzothiazole-2-base |
| Intermediate No. | R 3 |
| 23 | 5-methylbenzothiazole-2-base |
| 24 | Pyridine-2-base |
| 25 | 7-chloro benzothiazole-2-base |
| 26 | 5-methyl furan-2-base |
| 27 | 1-methyl-pyrroles-2-base |
| 28 | 4-methylthiazol-2-base |
| 29 | Oxazole-2-base |
| 30 | 1-Methylimidazole-2-base |
| 31 | Isothiazole-3-base |
| 32 | Isothiazole-4-base |
| 33 | Isoxazole-5 base |
| 34 | 1-ethyl pyrazoles-4-base |
| 35 | 5-chlorobenzene and furans-2-base |
| 36 | 6-methyl benzo plug fen 2-base |
| 37 | 1-skatole-2-base |
| 38 | 1-ethylindole-3 base |
| 39 | 5-oxyethyl group thiophene-2-base |
| 40 | 5-(2,2,2-trifluoro ethoxy) thiophene-2-base |
| 41 | 5-methyl thio-furan-2-base |
| 42 | 6-sulfonyloxy methyl pyridin-3-yl |
| 43 | 5-5-flumethiazine-2-base |
| 44 | 3-chloro-5-5-flumethiazine-2 base |
| 45 | 5-trifluoromethyl benzo thiazol-2-yl |
| 46 | 7-phenoxy group benzothiazole-2-base |
| 47 | 5-phenyl thiophene-2-base |
| 48 | Benzisothiazole-3-base |
| 49 | Benzisothiazole-3-base |
| Intermediate No. | R 3 |
| 50 | The 1-skatole |
| 51 | 6-trifluoromethoxy benzaldehyde and thiazol-2-yl |
| 52 | 7-fluoro benzothiazole-2 base |
| 53 | 7-bromo benzothiazole-2-base |
| 54 | 5-tertiary butyl thiophene-2-base |
| 55 | 7-(5-trifluoromethyl-2-pyridyloxy)-thionaphthene-2-base |
| 56 | 5-(5-trifluoromethyl-2-pyridyloxy)-thiophene-2-base |
| 57 | 2-(4-pyridyl) pyridine-5-base |
| 58 | 2-chloropyridine-5-base |
| 59 | 7-methylbenzothiazole-2-base |
| 60 | 6-methylbenzothiazole-2-base |
| 61 | 5-methoxyl group benzo oxazole-2-base |
| 62 | 4-fluoro benzothiazole-2-base |
| 63 | 4,7-dichlorobenzothiazole-2-base |
Table 1-2
| Intermediate No. | R 3 | Physical properties |
| 101 | Thiophene-2-base | Oily matter |
| 102 | 5-chlorothiophene-2-base | Oily matter |
| 103 | Thiene-3-yl- | Oily matter |
| 104 | Thionaphthene-2-base | Oily matter |
| 105 | Thionaphthene-3-base | Oily matter |
| 106 | Cumarone-2-base | Oily matter |
| 107 | Benzothiazole-2-base | Oily matter |
| 108 | 4-oxygen benzothiazole-2-base | Oily matter |
| 109 | 4-methylbenzothiazole-2-base | Oily matter |
| 110 | 4-methoxyl group benzo thiazol-2-yl | Oily matter |
| 111 | 6-methoxyl group benzo thiazol-2-yl | Oily matter |
| 112 | 5-chloro benzothiazole-2-base | m.p.76-77℃ |
| 113 | 6-oxygen benzothiazole-2-base | Oily matter |
| 114 | 5-fluoro benzothiazole-2-base | Oily matter |
| 115 | 5-(trifluoromethyl) thionaphthene-2-base | Oily matter |
| 116 | Benzoxazole-2-base | Oily matter |
| 117 | 5-Lv benzoxazole-2-base | m.p.84-91℃ |
| 118 | 6-Jia base benzoxazole-2-base | Oily matter |
| 119 | 1-tolimidazole-2-base | m.p.61-65℃ |
| 120 | 1-normal-butyl benzo imidazoles-2-base | Oily matter |
| 121 | 5-chloro-1-tolimidazole-2-base | Oily matter |
| 122 | 6-fluoro benzothiazole-2-base | Oily matter |
| Intermediate No. | R 3 | Physical properties |
| 123 | 5-methylbenzothiazole-2-base | Brown solid |
| 124 | Pyridine-2-base | Oily matter |
| 125 | 7-chloro benzothiazole-2-base | Oily matter |
| 126 127 | 5-methyl furan-2-base | |
| 1-methylpyrrole-2-base | ||
| 128 | 4-methylthiazol-2-base | |
| 129 | Oxazole-2-base | |
| 130 | 1-Methylimidazole-2-base | |
| 131 | Isothiazole-3-base | |
| 132 | Isothiazole-4-base | |
| 133 | Isoxazole-5-base | |
| 134 | 1-ethyl pyrazoles-4-base | |
| 135 | 5-chlorobenzene and furans-2-base | |
| 136 | 6 methylbenzene thiophthene-2-base | |
| 137 | 1-skatole-2-base | |
| 138 | 1-ethylindole-3-base | |
| 139 | 5-ethoxy thiophene-2-base | |
| 140 | 5-(2,2, the 2-trifluoro ethoxy) thiophene-2-base | |
| 141 | 5-methylpyrimidine-2-base | |
| 142 | 6-sulfonyloxy methyl pyridin-3-yl | |
| 143 | 5-5-flumethiazine-2-base | |
| 144 | 3-chloro-5-5-flumethiazine-2-base | Oily matter |
| 145 | 7-trifluoromethyl benzo thiazol-2-yl | |
| 146 | 7-phenoxy group benzothiazole-2-base | |
| 147 | 5-phenyl thiophene-2-base | |
| 148 | Benzisothiazole-3-base | |
| 149 | Benzoisoxazole-3-base |
| Intermediate No. | R 3 | Physical properties |
| 150 | 1-skatole-3-base | |
| 151 | 6-trifluoromethoxy benzaldehyde and thiazol-2-yl | |
| 152 | 7-fluoro benzothiazole-2-base | |
| 153 | 7-bromo benzothiazole-2-base | Oily matter |
| 154 | 5-tertiary butyl thiophene-2-base | Oily matter |
| 155 | 7-(5-trifluoromethyl-2-pyridyloxy) thionaphthene-2-base | |
| 156 | 5-(5-trifluoromethyl-2-pyridyloxy) thiophene-2-base | |
| 157 | 2-(4-pyridyloxy) pyridine-5-base | Oily matter |
| 158 | 2-chloropyridine-5-base | Oily matter |
| 159 | 7-methylbenzene thiophthene-2-base | Oily matter |
| 160 | 6-thionaphthene-2-base | m.p.60-61℃ |
| 161 | 5-methoxyl group benzo oxazole-2-base | m.p.105-106℃ |
| 162 | 4-fluoro benzothiazole-2-base | Oily matter |
| 163 | 4,7-dichlorobenzothiazole-2-base | Oily matter |
Table 1-3
| Intermediate No. | R 3 | Physical properties |
| 201 | Thiophene-2-base | m.p.143-144℃ |
| 202 | 5-chlorothiophene-2-base | m.p.90-93℃ |
| 203 | Thiene-3-yl- | m.p.147-152℃ |
| 204 | Thionaphthene-2-base | m.p.131-133℃ |
| 205 | Thionaphthene-3-base | Oily matter |
| 206 | Cumarone-2 base | m.p.150-156℃ |
| 207 | Thionaphthene-2-base | m.p.133-134℃ |
| 208 | 4-chloro benzothiazole-2-base | m.p.92-94℃ |
| 209 | 4-methylbenzothiazole-2-base | Oily matter |
| 210 | 4-methoxyl group benzo thiazol-2-yl | m.p.121-123℃ |
| 211 | 6-methoxyl group benzo thiazol-2-yl | m.p.155-157℃ |
| 212 | 5-chloro benzothiazole-2-base | m.p.141-142.5℃ |
| 213 | 6-chloro benzothiazole-2-base | m.p.148-150℃ |
| 214 | 5-fluoro benzothiazole-2-base | m.p.125-126℃ |
| 215 | 5-(trifluoromethyl) thionaphthene-2-base | m.p.140-142℃ |
| 216 | Benzoxazole-2-base | m.p.161-163℃ |
| 217 | 5-Lv benzoxazole-2-base | m.p.144-148℃ |
| 218 | 6-Jia base benzoxazole-2-base | m.p.116-118℃ |
| 219 | 1-tolimidazole-2-base | m.p.257-258℃ |
| 220 | 1-normal-butyl benzo thiazol-2-yl | m.p.180-181℃ |
| 221 | 5-chloro-1-tolimidazole-2-base | m.p.228-230℃ |
| 222 | 6-fluoro benzothiazole-2-base | Oily matter |
| Intermediate No. | R 3 | Physical properties |
| 223 | 5-methylbenzothiazole-2-base | m.p.150-152℃ |
| 224 | Pyridine-2-base | m.p.9(-100℃ |
| 225 | 7-chloro benzothiazole-2-base | m.p.139-141℃ |
| 226 | 5-methyl furan-2-base | |
| 227 | 1-methylpyrrole base-2-base | |
| 228 | 4-methylthiazol-2-base | |
| 229 | Oxazole-2-base | |
| 230 | 1-Methylimidazole-2-base | |
| 231 | Different thiene-3-yl- | |
| 232 | Different thiophene-4-base | |
| 233 234 | Different thiophene-5-base | |
| 1-ethyl pyrazoles-4-base | ||
| 235 | 5-chlorobenzene and furans-2-base | |
| 236 | 6-methylbenzene thiophthene-2-base | |
| 237 | 1-skatole-2-base | |
| 238 | 1-ethylindole-3-base | |
| 239 | 5-oxyethyl group thiophene-2-base | |
| 240 | 5-(2,2, the 2-trifluoro ethoxy) thiophene-2-base | |
| 241 | 5-thiotolene-2-base | |
| 242 | 6-sulfonyloxy methyl yl pyridines-3-exists | |
| 243 | 5-5-flumethiazine-2-base | |
| 244 | 3-fluoro-5-5-flumethiazine-2-base | m.p.118-135℃ |
| 245 | 7-trifluoromethyl thionaphthene-2-base | |
| 246 | 7-phenoxy group thionaphthene-2-base | |
| 247 | 5-phenyl thiophene-2-base | |
| 248 | Benzisothiazole-3-base | |
| 249 | Benzoisoxazole-3-base |
| Intermediate No. | R 3 | Physical properties |
| 250 | 1-skatole-3-base | |
| 251 | 6-trifluoromethoxy benzo thiazol-2-yl | |
| 252 | 7-fluoro benzothiazole-2-base | |
| 253 | 7-bromo benzothiazole-2-base | m.p.133-136℃ |
| 254 | 5-tertiary butyl thiophene-2-base | m.p.95-98℃ |
| 255 | 7-(5-trifluoromethyl-2-pyridyloxy) thionaphthene-2-base | |
| 256 | 5-(5-trifluoromethyl-2-pyridyloxy) thiophene-2-base | |
| 257 | 2-(4-pyridyloxy) pyridine-5-base | |
| 258 | 2-chloropyridine-5-base | m.p.111-113℃ |
| 259 | 7-methylbenzothiazole-2-base | m.p.142-143℃ |
| 260 | 6-methylbenzothiazole-2-base | m.p.149-151℃ |
| 261 | 5-methoxyl group benzo oxazole-2-base | m.p.161-162℃ |
| 262 | 4-fluoro benzothiazole-2-base | |
| 263 | 4,7-dichlorobenzothiazole-2-base |
Table 1-4
| Intermediate No. | R 3 | Physical properties |
| 301 | Thiophene-2-base | b.p.73-774℃/ 7mmHg |
| 302 | 5-chlorothiophene-2-base | m.p.90-93℃ |
| 303 | Thiene-3-yl- | Oily matter |
| 304 | Thionaphthene-2-base | Oily matter |
| 305 | Thionaphthene-3-base | Oily matter |
| 306 | Cumarone-2-base | Oily matter |
| 307 | Benzothiazole-2-base | m.p.44-46℃ |
| 308 | 4-chloro benzothiazole-2-base | m.p.95-97℃ |
| 309 | 4-methylbenzothiazole-2-base | Oily matter |
| 310 | 4-methoxyl group benzo thiazol-2-yl | m.p.8(-91℃ |
| 311 | 6-methoxyl group benzo thiazol-2-yl | Oily matter |
| 312 | 5-chloro benzothiazole-2-base | m.p.9(-101℃ |
| 313 | 6-chloro benzothiazole-2-base | m.p.74-76℃ |
| 314 | 5-fluoro benzothiazole-2-base | m.p.86-87℃ |
| 315 | 5-(trifluoromethyl) benzothiazole-2-base | Oily matter |
| 316 | Benzoxazole-2-base | Oily matter |
| 317 | 5-Lv benzoxazole-2-base | m.p.80-83℃ |
| 318 | 6-Jia base benzoxazolyl-2-base | m.p.5(-61℃ |
| 319 | 1-tolimidazole-2-base | m.p.88-91℃ |
| 320 | 1-normal-butyl benzo imidazoles-2-base | Oily matter |
| 321 | 5-chloro-1-tolimidazole-2-base | m.p.72-74℃ |
| Intermediate No. | R 3 | Physical properties |
| 322 | 6-trifluoro benzo thiazol-2-yl | Oily matter |
| 323 | 5-methylbenzothiazole-2-base | m.p.68-74℃ |
| 324 | Pyridine-2-base | Oily matter |
| 325 | 7-chloro benzothiazole-2-base | m.p.69-71℃ |
| 326 | 5-methyl furan-2-base | |
| 327 | 1-methylpyrrole-2-base | |
| 328 | 4-methylthiazol-2-base | |
| 329 | Oxazole-2-base | |
| 330 | 1-Methylimidazole-2-base | |
| 331 | Isothiazole-3-base | |
| 332 | Isothiazole-4-base | |
| 333 | Isoxazole-5-base | |
| 334 | 1-ethyl pyrazoles-4-base | |
| 335 | 5-chlorobenzene and furans-2-base | |
| 336 | 6-methylbenzene thiophthene-2-base | |
| 337 | 1-skatole-2-base | |
| 338 | 1-ethylindole-3-base | |
| 339 | 5-oxyethyl group thiophene-2-base | |
| 340 | 5-(2,2, the 2-trifluoro ethoxy) thiophene-2-base | |
| 341 | 5-thiomethylfuran-2-base | |
| 342 | 6-methyl sulphonyl pyridin-3-yl | |
| 343 | 5-5-flumethiazine-2-base | |
| 344 | 3-fluoro-5-5-flumethiazine-2-base | Oily matter |
| 345 | 7-trifluoromethyl benzo thiazol-2-yl | |
| 346 | 7-phenoxy group benzothiazole-2-base | |
| 347 | 5-phenyl thiophene-2-base | |
| 348 | Benzisothiazole-3-base |
| Intermediate No. | R 3 | Physical properties |
| 349 | Benzoisoxazole-3-base | |
| 350 | 1-skatole-3-base | |
| 351 | 6-trifluoromethoxy benzo thiazol-2-yl | |
| 352 | 7-fluoro benzothiazole-2-base | |
| 353 | 7-bromo benzothiazole-2-base | m.p.74-75℃ |
| 354 | 5-tertiary butyl thiophene-2-base | Oily matter |
| 355 | 7-(5-trifluoromethyl-2-pyridyloxy) benzothiazole-2-base | |
| 356 | 5-(5-trifluoromethyl-2-pyridyloxy) thiophene-2-base | |
| 357 | 2-(4-pyridyloxy) pyridine-5-base | |
| 358 | 2-chloropyridine-5-base | |
| 359 | 7-methylbenzene thiophthene-2-base | Oily matter |
| 360 | 6-methylbenzene thiophthene-2-base | m.p.69-70℃ |
| 361 | 5-methoxyl group benzo thiazol-2-yl | Oily matter |
| 262 | Fluoro benzothiazole-2-base | |
| 363 | 4,7-dichlorobenzothiazole-2-base |
Table 1-5R
3-CH
2CN (VII)
| Intermediate No. | R 3 | Physical properties |
| 401 | 5-chlorothiophene-2-base | Oily matter |
| 402 | Thionaphthene-2-base | The brown crystallization |
| 403 | Cumarone-2-base | m.p.50-52℃ |
| 404 | 4-chloro benzothiazole-2-base | m.p.119-121℃ |
| 405 | 4-methylbenzothiazole-2-base | m.p.168-170℃ |
| 406 | 4-methoxyl group benzo thiazol-2-yl | m.p.138-140℃ |
| 407 | 6-methoxyl group benzo thiazol-2-yl | m.p.70-72℃ |
| 408 | 5-chloro benzothiazole-2-base | m.p.150-152℃ |
| 409 | 6-chloro benzothiazole-2-base | m.p.72-74℃ |
| 410 | 5-fluoro benzothiazole-2-base | m.p.124-128℃ |
| 411 | 5-(trifluoromethyl) benzothiazole-2-base | m.p.90-92℃ |
| 412 | Benzoxazole-2-base | m.p.65-67℃ |
| 413 | 5-Lv benzoxazole-2-base | m.p.107-110℃ |
| 414 | 6-Jia base benzoxazole-2-base | m.p.115-116.5℃ |
| 415 | 1-tolimidazole-2-base | |
| 416 | 1-normal-butyl benzo thiazol-2-yl | Oily matter |
| 417 | 5-chloro-1-tolimidazole-2-base | |
| 418 | 6-fluoro benzothiazole-2-base | Oily matter |
| 419 | 5-methylbenzothiazole-2-base | Oily matter |
| 420 | 7-chloro benzothiazole-2-base | m.p.112-113℃ |
| 421 | 5-methyl furan-2-base | |
| 422 | 1-methylpyrrole-2-base | |
| 423 | 4-methylthiazol-2-base | |
| 424 | Oxazole-2-base | |
| 425 | 1-Methylimidazole-2-base |
| Intermediate No. | R 3 | Physical properties |
| 426 | Isothiazole-3-base | |
| 427 | Different thiophene-4-base | |
| 428 | Isoxazole-5-base | |
| 429 | 1-ethyl pyrazoles-4-base | |
| 430 | 5-chlorobenzene and furans-2-base | |
| 431 | 6-methylbenzene thiophthene-2-base | |
| 432 | 1-skatole-2-base | |
| 433 | 1-ethylindole-3-base | |
| 434 | 5-oxyethyl group thiophene-2-base | |
| 435 | 5-(2,2, the 2-trifluoro ethoxy) thiophene-2-base | |
| 436 | 5-thiomethylfuran-2-base | |
| 437 | 6-methylsulfonyl pyridin-3-yl | |
| 438 | 5-5-flumethiazine-2-base | |
| 439 | 3-chloro-5-5-flumethiazine-2-base | Oily matter |
| 440 | 7-trifluoromethyl benzo thiazol-2-yl | |
| 441 | 7-phenoxy group benzothiazole-2-base | |
| 442 | 5-phenyl thiophene-2-base | |
| 443 | Benzisothiazole-3-base | |
| 444 | Benzoisoxazole-3-base | |
| 445 | 1-skatole-3-base | |
| 446 | 6-trifluoromethoxy benzo thiazol-2-yl | |
| 447 | 7-fluoro benzothiazole-2-base | |
| 448 | 7-bromo benzothiazole-2-base | m.p.116-118℃ |
| 449 | 5-tertiary butyl thiophene-2-base | Oily matter |
| 450 | 7-(5-trifluoromethyl-2-pyridyloxy) benzothiazole-2-base |
| Intermediate No. | R 3 | Physical properties |
| 451 | 5-(5-trifluoromethyl-2-pyridyloxy) benzothiazole-2-base | |
| 452 | 2-(4-pyridyloxy) pyridine-5-base | |
| 453 | 2-chloropyridine-5-base | |
| 454 | 7-methylbenzothiazole-2-base | m.p.66-70℃ |
| 455 | 6-methylbenzothiazole-2-base | m.p.83-85℃ |
| 456 | 5-methoxyl group benzo oxazole-2-base | m.p.82-84℃ |
| 457 | 4-fluoro benzothiazole-2-base | |
| 458 | 4,7-dichlorobenzothiazole-2-base |
Now list the representational embodiment of formula of the present invention (I) compound in table 2.
Table 2
| Compound N o. | R 1 | R 2 | R 3 | Physical properties |
| 1 | Phenyl | Methyl | Benzothiazole-2-base | m.p.166-168℃ |
| 2 | Phenyl | Methyl | 5-fluoro benzothiazole-2-base | m.p.154.5-156℃ |
| 3 | Phenyl | Methyl | 7-chloro benzothiazole-2-base | m.p.115.5-118℃ |
| 4 | Phenyl | Methyl | Benzoxazole-2-base | Yellow oil |
| 5 | Phenyl | Methyl | Thionaphthene-2-base | Transparent oily matter |
| 6 | Phenyl | Methyl | 5-chlorothiophene-2-base | Transparent oily matter |
| 7 | Phenyl | Methyl | Thiene-3-yl- | m.p.85-88℃ |
| 8 | Phenyl | Methyl | Pyridine-2-base | Yellow oil |
| 9 | Phenyl | Methyl | 6-methoxyl group benzo thiazol-2-yl | m.p.160-162℃ |
| 10 | Phenyl | Methyl | 5-methyl furan-2-base | |
| 11 | Phenyl | Methyl | 1-methylpyrrole-2-base | |
| 12 | Phenyl | Methyl | 4-methylthiazol-2-base | |
| 13 | Phenyl | Methyl | Oxazole-2-base | |
| 14 | Phenyl | Methyl | 1-Methylimidazole-2-base | |
| 15 | Phenyl | Methyl | Isothiazole-3-base | |
| 16 | Phenyl | Methyl | Isothiazole-4-base | |
| 17 | Phenyl | Methyl | Isoxazole-5-base | |
| 18 | Phenyl | Methyl | 1-ethyl pyrazoles-4-base | |
| 19 | Phenyl | Methyl | 5-chlorobenzene and furans-2-base | |
| 20 | Phenyl | Methyl | 6-methylbenzene thiophthene-2-base | |
| 21 | Phenyl | Methyl | 1-skatole-2-base |
| Compound N o. | R 1 | R 2 | R 3 | Physical properties |
| 22 | Phenyl | Methyl | 1-ethylindole-3-base | |
| 23 | Phenyl | Methyl | 5-oxyethyl group thiophene-2-base | |
| 24 | Phenyl | Methyl | 5-(2,2, the 2-trifluoro ethoxy) thiophene-2-base | |
| 25 | Phenyl | Methyl | 5-thiomethylfuran-2-base | |
| 26 | Phenyl | Methyl | 6-methylsulfonyl pyridin-3-yl | |
| 27 | Phenyl | Methyl | 5-5-flumethiazine-2-base | Oily matter |
| 28 | Phenyl | Methyl | 3-chloro-5-5-flumethiazine-2-base | m.p.90-95℃ |
| 29 | Phenyl | Methyl | 6-chloro benzothiazole-2-base | Yellow oil |
| 30 | Phenyl | Methyl | 6-fluoro benzothiazole 2-base | Yellow oil |
| 31 | Phenyl | Methyl | 5-methylbenzothiazole-2-base | m.p.121-123℃ |
| 32 | Phenyl | Methyl | 6-methoxyl group benzo oxazole-2-base | |
| 33 | Phenyl | Methyl | 7-trifluoromethyl benzo thiazole-2-base | |
| 34 | Phenyl | Methyl | 7-phenoxy group benzothiazole-2-base | |
| 35 | Phenyl | Methyl | 5-thionaphthene-2-base | |
| 36 | Phenyl | Methyl | Benzisothiazole-3-base | |
| 37 | Phenyl | Methyl | Benzisothiazole-2-base | |
| 38 | Phenyl | Methyl | 1-skatole-3-base | |
| 39 | The 2-fluorophenyl | Methyl | 7-chloro benzothiazole-2-base | |
| 40 | Phenyl | Trifluoromethyl | Benzothiazole-2-base |
| Compound N o. | R 1 | R 2 | R 3 | Physical properties |
| 41 | The 2-phenylfluoroform | Methyl | 7-chloro benzothiazole-2-base | |
| 42 | The 2-anisole | Ethyl | Thiophene-2-base | |
| 43 | The 4-methylthio phenyl | Methyl | Furans-2-base | |
| 44 | 3-methylsulfonyl benzene | Methyl | Thiene-3-yl- | |
| 45 | Phenyl | Propyl group | Benzothiazole-2-base | Oily matter |
| 46 | Phenyl | The tertiary butyl | Benzothiazole-2-base | |
| 47 | Phenyl | Methyl | 6-trifluoromethoxy benzaldehyde and thiazole-2-base | |
| 48 | Phenyl | Methyl | 4-chloro benzothiazole-2-base | m.p.1 65-167℃ |
| 49 | Phenyl | Methyl | 5-chloro benzothiazole-2-base | m.p.145-148℃ |
| 50 | Phenyl | Methyl | 7-fluoro benzothiazole-2-base | |
| 51 | Phenyl | Methyl | 7-bromo benzothiazole-2-base | m.p.190-191℃ |
| 52 | Phenyl | Methyl | 5-tertiary butyl thiophene-2-base | |
| 53 | The 2-fluorobenzene | Ethyl | 7-chloro benzothiazole-2-base | |
| 54 | The 2-fluorobenzene | Methyl | 7-(5-trifluoromethyl-2-pyridyloxy) benzothiazole 2 bases | |
| 55 | Phenyl | Methyl | 5-(5-trifluoromethyl-2-pyridyloxy) benzothiazole-2-base | |
| 56 | Phenyl | Methyl | 2-(4-pyridyloxy) pyridine-5-base | |
| 57 | Phenyl | Methyl | 2-chloropyridine-5-base | Oily matter |
| Compound N o. | R 1 | R 3 | R 3 | Physical properties |
| 58 | Phenyl | Ethyl | Benzothiazole-2-base | Oily matter |
| 59 | Phenyl | Ethyl | 7-chloro benzothiazole-2-base | Oily matter |
| 60 | Phenyl | Propyl group | 7-chloro benzothiazole-2-base | Oily matter |
| 61 | Phenyl | Methyl | 7-methylbenzothiazole-2-base | Oily matter |
| 62 | Phenyl | Methyl | 6-methylbenzothiazole-2-base | m.p.154-155℃ |
| 63 | Phenyl | Methyl | 5-methoxyl group benzo oxazole-2-base | m.p.165-167℃ |
| 64 | Phenyl | Methyl | 4-methylbenzothiazole-2-base | m.p.154-159℃ |
| 65 | Phenyl | Methyl | 4-methoxyl group benzo thiazol-2-yl | m.p.55-60℃ |
| 66 | Phenyl | Methyl | 4-fluoro benzothiazole-2-base | m.p.137-142℃ |
| 67 | Phenyl | Methyl | 4,7-dichlorobenzothiazole-2-base | m.p.154-157℃ |
| 68 | Phenyl | Methyl | 6-bromo-4-fluoro benzothiazole-2-base | m.p.57-63℃ |
To list test implementation example of the present invention below.
Test implementation example 1
Water paddy soil is placed 1/10, in 000 are of basin, and sowing barnyard grass (Echinochloa, crusgalli) and the seed of Japanese nutgrass flatsedge (Scirpus juncoides), cover the thin soil of one deck again, then basin is moved into the greenhouse, irrigating the depth of water is 0.5 to 1cm, after two days, plantation Sagittaria pygmaea (Sagittaria pygmaea) stem tuber.In 1/10,000 an are of basin that splits, place soil by same procedure, slurry and smooth is stirred in pouring then, and second day, seed rice length translated into three rice shoots of every basin to 2 leaf phases.Then, water water irrigating depth and remain on the 3-4cm level, when barnyard grass and Japanese nutgrass flatsedge long to 0.5 leaf phase, after Sagittaria pygmaea length is transplanted four days to phase in early years and rice, drip the diluting soln of making by common preparation method that contains the The compounds of this invention wettable powder in the same manner with inhaling ball, make the dosage of active constituent reach predeterminated level.
Use weedicide after the 17th to 20 day, the making plant growth reaches by following level observes herbicidal effect and toxicity, the results are shown in table 3.
The herbicidal effect phytotoxicity
(preventing and treating extent of growth %)
5 (100) do not have
T (96-99) is slight
5-4 (91-95) is a small amount of
5-4 (85-90) is medium
4-5 (81-84) is serious
4 (71-80)
3 (51-70)
2 (31-50)
1 (0-30)
Table 3
| Compound N o. | Active constituent dosage (g/a) | Herbicidal effect | Toxicity to rice | ||
| Barnyard grass | The Japan nutgrass flatsedge | The short arrowhead of Japan | |||
| 1 | 10 5 | 5 5 | 5 5 | 4 2 | Do not have |
| 2 | 10 5 | 5 5 | 5-4 | 4 3 | Slight do not have |
| 3 | 10 5 | 5 5 | 2 1 | 1 1 | Do not have |
| 4 | 10 5 | 5 5 | 5 5 | 3 3 | Slight do not have |
| 5 | 10 5 | 5 5 | 1 1 | 1 1 | Do not have |
| 6 | 10 5 | 5 5 | 5-4 | 3 3 | Do not have |
| 7 | 10 5 | 5 5 | 5 4 | 2 1 | Slight do not have |
| 8 | 10 5 | 5-4 | 5-4 3 | 2 1 | Do not have |
| 31 | 10 | 5 | 3 | 2 | Do not have |
| Compound N o. | Active constituent dosage (g/a) | Herbicidal effect | Toxicity to rice does not have | ||
| Barnyard grass | The Japan nutgrass flatsedge | The short arrowhead of Japan | |||
| 5 | 3 | 1 | |||
| 48 | 10 5 | 5 5 | 3 2 | 2 2 | Do not have |
| 51 | 10 5 | 5 5 | 1 1 | 1 1 | Slight do not have |
| 59 | 10 5 | 5 5 | 2 2 | 3 3 | Do not have |
| 61 | 10 5 | 5 5 | 4 4 | 5-4 4 | Slight do not have |
| 66 | 10 5 | 5 5 | 5-4 5-4 | 5-4 4 | Slight do not have |
| 67 | 10 5 | 5 5 | 1 1 | 1 1 | Do not have |
Annotate:
EC: barnyard grass (Echinochloa crusgalli)
SH: Japanese Fischer grass (Scirpus juncoides)
SP: Sagittaria pygmaea (Sagittaria pygmaes) test implementation example 2
Place paddy soil in 1/10,000 are of basin, sowing barnya rdgrass (Echinochloa orusgalli) seed covers skim soil again.Then basin is placed room temperature, during the water depth of pouring be 0.5 to 1cm.Reach 2 leaves during the stage when this stage of coming into leaves, water the degree of depth of pouring water and change 3 to 4cm into, drip the diluting soln of the wettable powder that contains The compounds of this invention of preparation method preparation routinely in the same manner, make active ingredient dosage reach the expectation level with inhaling ball.
Use weedicide after 18 to 22 days, observe growing state, press identical level observation herbicidal effect in the test implementation example 1, the results are shown in table 4.
Table 4
Annotate:
| Compound N o. | The dosage of active constituent (g/a) | Herbicidal effect |
| EC | ||
| 1 | 10 5 2.5 | 5 5 5 |
| 2 | 10 5 2.5 | 5 5 5 |
| 3 | 10 5 2.5 | 5 5 5 |
| 4 | 10 5 | 5 5-4 |
| 5 | 10 5 | 5 5 |
| Compound N o. | The dosage of active constituent (g/a) 2.5 | Herbicidal effect |
| EC | ||
| 5 | ||
| 48 | 10 5 2.5 | 5 5 5 |
| 51 | 10 5 2.5 | 5 5 5 |
| 59 | 10 5 | 5 5 |
| 61 | 10 5 2.5 | 5 5 5 |
| 66 | 10 5 2.5 | 5 5 5 |
EC: barnyard grass (Echinochloa crusgalli) is hereinafter listed example of formulations of the present invention.Example of formulations 1 (1) compound N is 4.01 parts (weight) o.1
(2) 30.00 parts of bentonite (weight)
(3) lime carbonate 61.4 (part (weight)
(4) TOXANON GR-31A (producing) by Sanyo 3.00 parts of (weight) chemical industry Co., Ltd.
(5) 1.50 parts of calcium lignosulfonates (weight)
With the component (1) that ground in advance, (2) and (3) are mixed, sneak into component (4) and (5) and water again, miscellany extruding and become particle, drying and regulate size and obtain granule then.
Example of formulations 2
(1) 78 parts of Jeeklite (weight)
(2) Lavelin S (producing) by 2 parts of (weight) formulas of first industrial pharmacy strain commercial firm
(3) Sorpol 503 ((5 parts of (weight) Co., Ltd. produce by eastern nation chemical industry)
(4) 5 parts of noncrystalline silica 1s (weight)
By (: o.2 mixed above-mentioned component miscellany of 1 weight ratio and compound N obtain wettable powder.
Example of formulations 3
(1) compound N o.3 0.81 part (weight)
(2) 30.00 parts of bentonite (weight)
(3) lime carbonate 64.6 (part (weight)
(4) TOXANON GR-31A (as above institute's 3.00 parts (weight) states)
(5) 1.50 parts of calcium lignosulfonates (weight)
The mixed component (1) that grinds in advance, (2) and (3) sneak into component (4) and (5) and water again, miscellany is pushed form particle, then drying and regulate size and obtain granule.
Example of formulations 4
(1) compound N o.3 30.0 parts (weight)
(2) 60.0 parts of Jeeklite (weight)
(3) NK WG-1 (5.0 parts of Takemoto Oil and (weight)
Fat Co., Ltd generates)
(4) NK FS-7 (5.0 parts of Takemoto Oil and (weight)
Fat Co., Ltd generates)
Mixed component (1), grind then (2) and (3), adds component (4) miscellany again and rub up then that extruding forms particle, dry again and adjusting is big or small, obtains wetting properties particle pulvis.
Example of formulations 5
(1) compound N o.3. 1.30 parts (weight)
(2) 16.25 parts in pyrazoles oxygen phenol (weight)
(3) 10.73 parts of bromobutyraldehydes (weight)
(4) Soprophor FL (producing) by 2.00 parts of (weight) POULENC of RHONE
(5) Sorpol 355 (producing) by 1.50 parts of (weight) societies of chemistry strain formula meeting of eastern nation
(6) IP solvent 1620 (32.00 parts of (weight) Petrochemical of Idemitus Co., Ttd produces)
(7) 6.00 parts of 1 (weight)
(8) 30.22 parts in water (weight)
Mixed above-mentioned component also uses wet lapping machine (Dynomil) to grind, and obtains moisture aaerosol solution.
Claims (6)
1. the cyclic amide compounds of a formula (I):
R wherein
1Be phenyl, R
2Be C
1-8Alkyl, R
3Can be replaced by halogen atom
, can be replaced by halogen atom or trifluoromethyl
, or can be by halogen atom, C
1-8Alkyl or C
1-8Alkoxyl group replaces
, wherein D is Sauerstoffatom or sulphur atom.
2. cyclic amide as claimed in claim 1 is characterized in that in formula (I) R
3Be can be by halogen atom, C
1-8Alkyl or C
1-8Alkoxyl group replaces
Wherein D is Sauerstoffatom or sulphur atom.
3. cyclic amide as claimed in claim 1, be 3-[[1-(benzothiazole-2-yl)-1-methyl] ethyl]-2,3-dihydro-6-methyl-5-phenyl-4H-1,3-oxazine-4-ketone, 3-[[1-(5-fluoro benzothiazole-2-yl)-1-methyl] ethyl]-2,3-dihydro-6-methyl-5-phenyl-4H-1,3-oxazine-4-ketone, 3-[[1-(7-chloro benzothiazole-2-yl)-1-methyl] ethyl]-2,3-dihydro-6-methyl-5-phenyl-4H-1,3-oxazine-4-ketone, 3-[[1-(4-chloro benzothiazole-2-yl)-1-methyl] ethyl]-2,3-dihydro-6-methyl-5-phenyl-4H-1,3-oxazine-4-ketone, 3-[[1-(7-bromo benzothiazole-2-yl)-1-methyl] ethyl]-2,3-dihydro-6-methyl-5-phenyl-4H-1,3-oxazine-4-ketone, 3-[[1-(7-chloro benzothiazole-2-yl)-1-methyl] ethyl]-6-ethyl-2,3-dihydro-5-phenyl-4H-1,3-oxazine-4-ketone, 2,3-dihydro-6-methyl-3-[[1-(7-methylbenzothiazole-2-yl)-1-methyl] ethyl]-5-phenyl-4H-1,3-oxazine-4-ketone, 3-[[1-(4-fluoro benzothiazole-2-yl)-1-methyl] ethyl]-2,3-dihydro-6-methyl-5-phenyl-4H-1,3-oxazine-4-ketone, or 3-[[1-(4,7-dichlorobenzothiazole-2-yl)-1-methyl] ethyl]-2,3-dihydro-6-methyl-5-phenyl-4H-1,3-oxazine-4-ketone.
4. the preparation method of the cyclic amide compounds of formula (I):
R in the formula
1Be phenyl, R
2Be C
1-8Alkyl, R
3Can be replaced by halogen atom
Can be replaced by halogen atom or trifluoromethyl
Or can be by halogen atom, C
1-8Alkyl or C
1-8Alkoxyl group replaces
Wherein D is Sauerstoffatom or sulphur atom, and this method comprises that two oxa-s of formula (II) are because of compound
R wherein
1And R
2As above-mentioned qualification, R
8And R
9Be respectively C
1-8Alkyl, with the N-benzylidene amino compound reaction of formula (III),
R wherein
3As above limit.
5. herbicidal composition, contain at least a cyclic amide compound that is selected from formula (I) of herbicidally effective amount:
R wherein
1Be phenyl, R
2Be C
1-8Alkyl, R
3Can be replaced by halogen atom
Can be replaced by halogen atom or trifluoromethyl
Or can be by halogen atom, C
1-8Alkyl or C
1-8Alkoxyl group replaces
Wherein D is Sauerstoffatom or sulphur atom and agriculture auxiliary.
6. a herbicidal methods comprises the described herbicidal composition of 0.1 to 40g/a claim 5 is applied to plant.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP361733/1992 | 1992-12-15 | ||
| JP36173392 | 1992-12-15 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1091133A CN1091133A (en) | 1994-08-24 |
| CN1038682C true CN1038682C (en) | 1998-06-10 |
Family
ID=18474699
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN93112741A Expired - Fee Related CN1038682C (en) | 1992-12-15 | 1993-12-15 | Cyclic amide compounds, process for their production and their use as herbicides |
Country Status (8)
| Country | Link |
|---|---|
| EP (1) | EP0690857A1 (en) |
| KR (1) | KR950704306A (en) |
| CN (1) | CN1038682C (en) |
| AU (1) | AU5714494A (en) |
| BR (1) | BR9307666A (en) |
| MX (1) | MX9307874A (en) |
| TW (1) | TW253885B (en) |
| WO (1) | WO1994013665A1 (en) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5883283A (en) * | 1994-10-17 | 1999-03-16 | Novartis Finance Corporation | Process for the preparation of substituted 3-aminobenzonitriles |
| BR9611999A (en) * | 1995-12-11 | 1999-03-02 | Rhone Poulenc Agriculture | 1,3-oxazin-4-one derivative herbicidal composition method for weed control and process for the preparation of a 1,3-oxazin-4-one derivative |
| PT102162B (en) * | 1997-06-10 | 2001-05-31 | Rhone Poulenc Agriculture | HERBICIDES |
| EP2316820A1 (en) * | 2009-10-28 | 2011-05-04 | Dompe S.p.A. | 2-aryl-propionamide derivatives useful as bradykinin receptor antagonists and pharmaceutical compositions containing them |
| EP2655362A1 (en) | 2010-12-22 | 2013-10-30 | Abbvie Inc. | Hepatitis c inhibitors and uses thereof |
| CA3073810A1 (en) * | 2017-08-31 | 2019-03-07 | Ahammune Biosciences Private Limited | Thiophene-derived compounds, process for synthesis and use thereof |
| JP7326624B2 (en) * | 2020-07-07 | 2023-08-15 | 住友ファーマ株式会社 | benzisoxazole derivative |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH619931A5 (en) * | 1976-08-12 | 1980-10-31 | Ciba Geigy Ag | |
| JPS59172485A (en) * | 1983-03-18 | 1984-09-29 | Tetsuzo Kato | Production of 2,2-dimethyl-1,3-dioxin-4-one derivative |
| EG18833A (en) * | 1988-12-09 | 1994-11-30 | Kumiai Chemical Industry Co | Cyclic amide compounds and herbicides |
| JPH082884B2 (en) * | 1990-07-30 | 1996-01-17 | ダイセル化学工業株式会社 | 1,3-Oxazin-4-one derivative, its production method and plant growth inhibitor |
| JPH05201811A (en) * | 1992-01-29 | 1993-08-10 | Daicel Chem Ind Ltd | 2,3-dihydro-4h-1,3-oxazin-4-one derivative based herbicide |
| AU652310B2 (en) * | 1992-01-30 | 1994-08-18 | Bayer Cropscience K.K. | 1,3-oxazin-4-one derivative, herbicide containing the same, and novel intermediate for producing the same |
-
1993
- 1993-12-06 TW TW082110298A patent/TW253885B/zh active
- 1993-12-13 MX MX9307874A patent/MX9307874A/en unknown
- 1993-12-15 WO PCT/JP1993/001815 patent/WO1994013665A1/en not_active Application Discontinuation
- 1993-12-15 EP EP94903001A patent/EP0690857A1/en not_active Withdrawn
- 1993-12-15 CN CN93112741A patent/CN1038682C/en not_active Expired - Fee Related
- 1993-12-15 BR BR9307666A patent/BR9307666A/en not_active Application Discontinuation
- 1993-12-15 AU AU57144/94A patent/AU5714494A/en not_active Abandoned
- 1993-12-15 KR KR1019950702422A patent/KR950704306A/en not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| CN1091133A (en) | 1994-08-24 |
| KR950704306A (en) | 1995-11-17 |
| MX9307874A (en) | 1994-07-29 |
| BR9307666A (en) | 1999-08-24 |
| WO1994013665A1 (en) | 1994-06-23 |
| TW253885B (en) | 1995-08-11 |
| AU5714494A (en) | 1994-07-04 |
| EP0690857A1 (en) | 1996-01-10 |
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