CN1020391C - Fungicides preparing process - Google Patents
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- CN1020391C CN1020391C CN 88100636 CN88100636A CN1020391C CN 1020391 C CN1020391 C CN 1020391C CN 88100636 CN88100636 CN 88100636 CN 88100636 A CN88100636 A CN 88100636A CN 1020391 C CN1020391 C CN 1020391C
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Abstract
The present invention relates to a sterilization compound of a structural formula (I) and a stereo isomer thereof. R<1> is arbitrarily substituted aryl or arbitrarily substituted ceteroary, and y is oxygen and sulfur or NR<4>; R<2>, R<3> and R<4> can be identical or different, and R<2>, R<3> and R<4> are hydrogen and C1-4 alkyl or C2-4 alkenyl; X is halogen, the C1-4 alkyl, the C2-4 alkenyl, C1-4 alkoxy and nitryl or cyan, and n is an integer from 0 to 4. According to a specification, when y is the oxygen, n is 0 and R<1> is phenyl without being substituted, at least one of R<2> and R<3> is not the hydrogen or methyl.
Description
The invention relates to as the acrylic acid derivative of bactericide, prepare these derivatives method, contain the bactericidal composition of this analog derivative and use the method for this analog derivative sterilization, be particularly useful for the crop of fungal infection.
The invention provides the compound and the stereoisomer thereof of a kind of structural formula (I),
R wherein
1It is aryl that replaces arbitrarily or the heteroaryl that replaces arbitrarily; Y is oxygen, sulphur or NR
4; R
2, R
3And R
4Can be identical or different, they are hydrogen, C
1-4Alkyl or C
2-4Alkenyl; X is halogen (fluorine, chlorine, bromine or iodine), C
1-4Alkyl, C
2-4Alkenyl, C
1-4Alkoxyl, nitro or cyano group and n are integers of 0 or 1 to 4; Regulation when y be that oxygen, n are 0 and R
1Be when not having the phenyl of replacement, R
2And R
3In at least one can not be hydrogen or methyl.
The compound of the structural formula (I) that the invention provides as defined above on the one hand, wherein y is oxygen.
On the other hand, the invention provides as defined above, R wherein
1It is the compound of the structural formula (I) of any heteroaryl that replaces.
Also have on the one hand, the invention provides as defined above, R wherein
1Be that the aryl while y that replaces arbitrarily is NR
4The compound of structural formula (I).
Have again on the one hand, the invention provides as defined above, R wherein
1Be that the aryl, the y that replace arbitrarily are oxygen or sulphur and R
2And R
3Not the compound of the structural formula (I) of hydrogen entirely.
Have again on the one hand, the invention provides as defined above, wherein X is C
2-4The compound of the structural formula of alkenyl (I).
Compound of the present invention contains a carbon-to-carbon double bond at least, and this sometimes compound obtains with the form of geometric isomer mixture.Yet these mixtures can be separated into single isomer, the present invention includes such isomer, and the isomer mixture of various ratios comprises mainly the mixture of the various ratios of being formed and mainly being made up of (E) isomer by (Z)-isomer.
Usually use " (E) " and " (Z) " mark by the single isomer that the two keys of the asymmetric replacement of acrylate produce.According to Cahn Ingold-Prelog system definition " (E) " and " (Z) ", in the literature abundant detailed description having been done by this system (sees, for example, J March, " Advanced Organic Chemistry ", the 3rd edition, Wiley-Interscience, 109 pages and with the lower part).
Another isomer bactericidal activity height of common a kind of ratios of the isomers, the isomer with high bactericidal activity is general-CO
2CH
3With-OCH
3Group is in the two key both sides ((E)-isomer) of the alkene of acrylate.These (E)-isomer have been formed most preferred embodiment of the present invention.
Substituent R in the compound (I)
1It is aryl that replaces arbitrarily or the heteroaryl that replaces arbitrarily." aryl " especially comprises phenyl, and " aryl " also comprises naphthyl." heteroaryl " comprise 5 yuan of containing one or more hetero atom O, S and N or 6 yuan of heterocyclic groups (preferably hetero atom is S or N) and thick and the benzenoid form and the fragrant type ring system of mixing.R
1Example as heteroaryl group is pyridine radicals, pyrimidine radicals, pyrazinyl, pyridazinyl, 1,2,3-, 1,2,4-and 1,3,5-triazines base, 1,2,4,5-tetrazine base, thienyl, quinolyl, isoquinolyl, quinoxalinyl and benzothienyl.
The substituting group that can exist at the aryl that replaces arbitrarily and heteroaryl moieties comprises one or more following radicals, halogen, hydroxyl, C
1-4Alkyl (especially methyl, ethyl), C
2-4Alkenyl (especially pi-allyl), C
2-4Alkynyl group (especially propargyl), C
1-4Alkoxyl (especially methoxyl group), C
2-4Alkenyloxy (especially allyloxy), C
2-4Alkynyloxy group (especially alkynes propoxyl group), halo (C
1-4) alkyl (especially trifluoromethyl, trichloromethyl and chloro and bromomethyl), halo (C
1-4) alkoxyl (especially trifluoromethoxy), C
1-4Alkylthio group (especially methyl mercapto), hydroxyl (C
1-4) alkyl (especially methylol), (C
1-4) alcoxyl (C
1-4) alkyl, C
3-6Cycloalkyl, C
3-6Cycloalkyl (C
1-4) alkyl, the aryl (phenyl that replaces especially arbitrarily) that replaces arbitrarily, the heteroaryl (pyridine radicals or the pyrimidine radicals that replaces especially arbitrarily) that replaces arbitrarily, the aryloxy group (phenoxy group that replaces especially arbitrarily) that replaces arbitrarily, the heteroaryloxy (pyridine oxygen base or the 2-pyrimidinyl oxy that replaces especially arbitrarily) that replaces arbitrarily, the aryl (C that replaces arbitrarily
1-4) alkyl (benzyl that replaces, the phenethyl that replaces arbitrarily and the phenyl n-pro-pyl that replaces the arbitrarily especially arbitrarily) moieties heteroaryl (C that replaces arbitrarily, replace arbitrarily with hydroxyl wherein
1-4) alkyl (especially any pyridine radicals or pyrimidine radicals (C that replaces
1-4) alkyl), the aryl (C that replaces arbitrarily
2-4) alkenyl (especially arbitrarily replace styryl), the heteroaryl (C that replaces arbitrarily
2-4) alkenyl (especially arbitrarily replace pyridine acetylene or pyrimidine acetenyl), the aryl (C that replaces arbitrarily
1-4) alkoxyl (especially arbitrarily replace benzyloxy), the heteroaryl (C that replaces arbitrarily
1-4) alkoxyl (especially any pyridine or pyrimidine radicals (C that replaces
1-4) alkoxyl), the aryloxy group (C that replaces arbitrarily
1-4) alkyl (especially arbitrarily replace Phenoxymethyl), the assorted fragrant oxygen (C that replaces arbitrarily
1-4) alkyl (especially any pyridine or 2-pyrimidinyl oxy (C that replaces
1-4) alkyl), acyloxy (especially acetoxyl group and benzoyloxy), cyano group, thiocyano, nitro ,-NR ' R " ,-NHCOR ' ,-NHCONR ' R " ,-CONR ' R " ,-COOR ', OSO
2R ' ,-SO
2R ' ,-COR ' ,-CR '=NR " or-N=CR ' R " wherein R ' and R " are respectively hydrogen, C
1-4Alkyl, C
1-4Alkoxyl, C
1-4Alkylthio group, C
3-6Cycloalkyl, C
3-6Cycloalkyl (C
1-4) alkyl, the aryl (phenyl that replaces especially arbitrarily) that replaces arbitrarily or the aryl (C that replaces arbitrarily
1-4) alkyl (benzyl that replaces especially arbitrarily).One or more aryl and the heteroaryl on the substituting group that the aryl that replaces arbitrarily and heteroaryl moieties can exist comprises, just described.
Therefore, on the other hand, the invention provides the compound of structural formula (I), wherein R as defined above
1Be with one or more hydroxyls, C
3-6Cycloalkyl (C
1-4) alkyl, aryl (C
1-4) alkoxyl, aryloxy group (C
1-4) aryl that alkyl, acyloxy, CR '=NR " or N=CR ' R " replace arbitrarily, R ' and R " are respectively hydrogen C simultaneously
1-4Alkylthio group, C
3-6Cycloalkyl, C
3-6Cycloalkyl (C
1-4) alkyl, phenyl or benzyl, phenyl and benzyl are with halogen, C
1-4Alkyl or C
1-4Alkoxyl replaces arbitrarily.
Also have on the other hand, the invention provides structural formula (I) compound, wherein R as defined above
1Be with one or more NR ' R ", NHCOR ', NHCONR ' R ", CONR ' R ", CO
2R ', OSO
2R ', SO
2The aryl that R ' or COR ' replace arbitrarily, R ' is C
3-6Cycloalkyl (C
1-4) alkyl or benzyl and R " be hydrogen, C
1-4Alkylthio group, C
3-6Cycloalkyl, C
3-6Cycloalkyl (C
1-4) alkyl, phenyl or benzyl, phenyl and benzyl group are by halogen, C
1-4Alkyl or C
1-4Alkoxyl replaces arbitrarily.
Also have on the other hand, the invention provides structural formula (I is (the E)-isomer of compound a):
Wherein Ab is selected from these groups: the 2-bromine; 3-iodine; The 2-ethyl; The 3-isopropyl; 3-just-butyl; The 3-trifluoromethoxy; 3-amino; The 4-phenyl; The 2-carboxyl; The 3-methoxycarbonyl; The 2-hydroxyl; 2, the 3-difluoro; 3, the 5-difluoro; 2, the 3-dimethoxy; 2-fluoro-4-chlorine; 2-chloro-5-fluorine; 2-fluoro-6-methyl; 3-methyl-4-fluorine; 3-fluoro-5-methoxyl group; 2-methoxyl group-3-fluorine; 2-chloro-4-methyl; The 2-methyl-5-chloro; 2-chloro-6-methoxyl group; 3-methoxyl group-4-chlorine; 3-methyl-5-methoxyl group; 2,4, the 5-trifluoro; 2,4, the 6-trichlorine; 2,4, the 6-trimethyl; 2,6-two fluoro-4-chlorine; 2,6-dimethyl-4-fluorine; 2,3,5, the 6-tetrachloro; Five fluorine and pentachloro-.
When at the substituting group of aryl or heteroaryl moieties during in the adjacent position, they can connect and form a condensed ring.This condensed ring or fragrance or aliphatic, contain one or more hetero atoms arbitrarily.Substituting group is connected to form the R of condensed ring
1Example is dibenzo-P-dioxinyl, thiophene
Base, phenoxathiin group, dibenzofuran group and dibenzothiophenes base.
When y is oxygen and R
1When being phenyl, preferably phenyl ring is substituted.When y is NR
4The time, best R
1Be substituted to reduce NR
4The basicity of nitrogen-atoms.This can realize by the substituting group as electron withdraw group.
Work as substituent R
2, R
3, R
4With any one of X be C
1-4Alkyl or C
1-4During alkoxyl, moieties can be the form of straight or branched, just alkyl can be methyl, ethyl, just or different-propyl group or just, secondary, the XOR tert-butyl group.Other C
1-4Alkyl and C
1-4Alkoxyl has same implication.
Work as substituent R
2, R
3, R
4With any one of X be C
2-4During alkenyl, it can be the form of straight or branched, and (E)-configuration or (Z)-configuration can be arranged when suitable.Such example be vinyl, pi-allyl ,-C(CH
3): CH
2(E) and (Z)-cyclobutenyl.Other C
2-4Alkenyl has same implication.
Optimal cases is R
2And R
3All be hydrogen and R
4Be hydrogen or methyl.
When n is 2 or more for a long time, substituent X can be identical or different.Yet general n preferably 0 or 1.
Also have on the other hand, the invention provides the compound of structural formula (I b), especially (E)-isomer:
Wherein y has the implication that provides in the past; M is an integer of 1 to 5; And A is halogen (especially fluorine or chlorine), hydroxyl, C
1-4Alkyl (especially methyl or ethyl), halo (C
1-4) alkyl (especially halogenated methyl, particularly trifluoromethyl, difluoromethyl, methyl fluoride or trichloromethyl), C
1-4Alkoxyl (especially methoxyl group), halo (C
1-4) alkoxyl (especially trifluoromethoxy), phenyl, phenoxy group, nitro, amino, acylamino-(especially formamido group and acetylamino), cyano group, carboxyl, C
1-4Alkoxy carbonyl group (especially methoxycarbonyl group) or C
1-4Alkyl carbonyl oxy (especially acetoxyl group).
When m is 2 or more for a long time, best situation is that substituent A (can be identical or different) is fluorine, chlorine, bromine, hydroxyl, methyl, trifluoromethyl, difluoromethyl, methyl fluoride, trichloromethyl, methoxyl group, nitro, cyano group, methoxycarbonyl group or methyl ketonic oxygen base.
When m is 2 or more for a long time, the example of substituent A m combination is difluoro, dichloro, dimethyl, dimethoxy, fluoro-chlorine, fluoro-2-methyl-, fluoro-methoxyl group, chloromethyl, chlorine methoxyl group, methyl methoxy base, trifluoro, trichlorine, trimethyl, two fluoro-chlorine, dimethyl-fluorine, tetrachloro and five fluorine.
On the other hand, the invention provides the compound of structural formula (I c), especially (E)-isomer:
Wherein B is N or CH; The implication that provides before y has; P is an integer (when B is N) of 0 or 1 to 3 or an integer (when B is CH) of 0 or 1 to 4; And A
1The implication of above having A being described.
The compound that reduces the basicity on the heterocyclic nitrogen atom is preferred.So best is that y links theheterocyclic nitrogen atom ortho position, perhaps substituent A
1(especially methoxyl group) links the theheterocyclic nitrogen atom ortho position, and perhaps two conditions all possess.
When p is 2 or more for a long time, best A
1Value be when m be 2 or described more for a long time best A value.When p is 2 or more for a long time, substituent A
1 pIn conjunction with example be difluoro, dichloro, dibromo, chloro-fluorine, two chloro-fluorine, bromo-fluorine, bromo-chlorine, fluoro-trifluoromethyl, chloro-trifluoromethyl, two chloro-trifluoromethyls, bromo-trifluoromethyl, fluoro-cyano group, chloro-cyano group, bromo-cyano group, dicyano, cyano group-trifluoro, chloro-hydroxyl, bromo-hydroxyl, chloro-methoxyl group, bromo-methoxyl group, chloro-nitro, cyano group-nitro, methoxyl group-nitro, nitro-trifluoromethyl, chloro-acetoxyl group, trifluoro, when B was CH, it was cyano group-trifluoro and tetrafluoro.
Another special aspects the invention provides (the E)-isomer of structural formula (I d) compound:
Wherein q is an integer of 0 or 1 to 5; D is halogen, hydroxyl, C
1-4Alkyl, halo (C
1-4) alkyl, C
1-4Alcoxyl benzene halo (C
1-4) alkoxyl or phenoxy group and E be hydrogen or halogen.
The aspect that another is special the invention provides (the E)-isomer of structural formula (I e) compound:
Wherein B is N or CH; R is an integer (when B is N) of 0 or 1 to 3, or an integer (when B is CH) of 0 or 1 to 4 and D and E definition are as above.
Also have another special aspect, the invention provides (the E)-isomer of structural formula (I f) compound:
Wherein A is 3-bromine, 3-chlorine or 4-chlorine.
The present invention is with the compound explanation of enumerating in the following table I.
The compound of following structural formula has also illustrated the present invention:
R wherein
1, R
2, R
3There is same implication to combine with X with each corresponding oxygen fluidization compound in table I (promptly when the y of compound (I) is oxygen) and has and show the implication that in the II compound provided for 1 to No. 3 below.
About R
1, R
2, R
3With the implication of X, No. 4 compounds of table II are corresponding to No. 1 compound of table I, and No. 5 compounds are corresponding to No. 67 compounds showing I.
The table II
Compound R
1X R
2R
3*+fusing point
Numbering isomer alkene (℃)
1 C
6H
5H H H
E7.60 69
2 C
6H
5H CH
3H
E
3 C
6H
5H CH
3CH
3 E
4 3-Cl-C
6H
4H H H
E7.60 85
5 pyridines-2-base H H H
E7.57 Oil
The chemical shift (ppm, tetramethylsilane) that the olefinic proton of+'beta '-methoxy acrylic acid ester is unimodal.As not having other explanation, solvent is CDCl
3
* the geometric isomer of 'beta '-methoxy acrylic acid ester.
The compound of following structural formula further specifies the present invention:
R wherein
1, R
2, R
3There is same implication to combine and R with X with each corresponding oxygen fluidization compound in table I (y that is compound (I) is an oxygen)
4Be (a) hydrogen and (b) methyl.
In addition, R
1, R
2, R
3, R
4With X the implication that provides in the following table III can be arranged.
The table IV
Table IV: the proton N MR data of selection
The table IV shows the proton N MR data of some compound selection of describing in his-and-hers watches I and the II.Except as otherwise noted, otherwise compound from the table I.Measure chemical shift from tetramethylsilane with ppm, use deuterochloroform as solvent.Use following abbreviation:
Br=broad peak t=triplet ppm=a few millionths
The unimodal q=quartet of s=
D=doublet m=multiplet
Compound number
29 1.28（9H，s），3.69（3H，s），3.81（3H，s），4.94（2H，s），6.7（1H，m），6.95（2H，m），7.15-7.4（4H，m），7.55（1H，m），7.57（1H，s）ppm.
37 3.70（3H，s），3.82（3H，s），3.90（3H，s），5.00（2H，s），7.04-7.36（5H，m，7.55-7.62（3H，m），7.59（1H，s）ppm.
160 3.70（3H，s），3.76（3H，s），3.82（3H，s），4.94（2H，s），6.5（3H，m），7.16（2H，m），7.35（2H，m），7.55（1H，m），7.58（1H，s）ppm.
Table IV (continuing)
Compound number
169 1.13（6H，t），3.31（4H，q），3.70（1H，s），3.82（3H，s），4.94（2H，s），6.2-6.35（3H，m），7.05-7.4（4H，m），7.56（1H，m），7.58（1H，s）ppm.
170 1.42（3H，t），3.69（3H，s），3.82（6H，s），4.05（2H，q），4.90（2H，s），6.36（1H，m），6.54（1H，m），6.74（1H，m），7.17（1H，m），7.32（2H，m），7.54（1H，m），7.57（1H，s）ppm.
172 3.70（3H，s），3.79（3H，s），3.82（3H，s），4.93（2H，s），6.5-6.7（6H，m），7.1-7.4（5H，m），7.52（1H，m），7.57（1H，s）ppm.
173 3.67（3H，s），3.78（3H，s），3.83（3H，s），4.91（2H，s），6.45-6.64（3H，m），6.88-7.38（8H，m），7.52（1H，m），7.57（1H，s）ppm.
174 3.68（3H，s），3.81（3H，s），5.31（2H，s），6.96（1H，s），7.07（1H，d），7.19（1H，m），7.30-7.40（2H，m），7.51-7.61（1H，m），7.57（1H，s），8.29（1H，d）ppm.
Table IV (continuing)
Compound number
179 3.71（3H，s），3.83（3H，s），5.04（2H，s），7.01-7.05（1H，m），7.17-7.62（12H，m），7.60（1H，s），8.41（1H，s）ppm.
181 2.32（3H，s），3.67（3H，s），3.79（3H，s），4.93（2H，s），7.57（1H，s）ppm.
182 3.67（3H，s），3.78（3H，s），4.93（2H，s），6.5（2H，m），6.65（1H，m），6.9-7.55（9H，m），7.57（1H，s）ppm.
183 3.67（3H，s），3.78（3H，s），4.94（2H，s），6.55（2H，m），6.68（1H，m），6.90（1H，m），7.10-7.38（7H，m），7.5（1H，m），7.58（1H，s）ppm.
184 3.68（3H，s），3.78（3H，s），4.94（2H，s），5.02（2H，s），6.55（3H，m），7.1-7.45（9H，m），7.55（1H，m），7.57（1H，s）ppm.
187 3.70（3H，s），3.83（3H，s），5.02（2H，s），6.84（1H，m），7.04（2H，m），7.20（2H，m），7.33-7.49（7H，m），7.63（1H，s）ppm.
Table IV (continuing)
Compound number
188 3.68（3H，s），3.82（3H，s），4.92（2H，s），6.45（1H，m），6.52（1H，m），6.61（1H，m），7.00-7.50（9H，m），7.59（1H，s）ppm.
226 3.72（3H，s），3.83（3H，s），5.01（2H，s），6.81（1H，d），7.04-7.39（11H，m），7.48-7.58（3H，m），7.59（1H，s）ppm.
232 3.68（3H，s），3.78（3H，s），3.88（2H，s），4.92（2H，s），6.68-6.77（3H，m），7.04-7.38（8H，m），7.48-7.55（1H，m），7.57（1H，s）ppm.
5 3.70（3H，s），3.83（3H，s），4.36（2H，
(table II) s), 6.94-7.00(1H, m), 7.08-7.16(2H, m), 7.22-7.30(2H, m), 7.40-7.56(2H, m), 7.57(1H, s), 8.43(1H, ddd) ppm.
The step preparation that the compound of structural formula of the present invention (I) can show in the V by the accompanying drawing I.R in whole these accompanying drawings
1, R
2, R
3, R
4, X and Y definition as above, R
5Be hydrogen or a kind of metal (as sodium or potassium), R is an alkyl, and L is a kind of leaving group such as halide (chloride, bromide or iodide), a kind of CH
3SO
4-anion or a kind of sulfonyloxy-anion, Z are halogen (iodine, bromine or chlorine).Change in suitable temperature and common, although always not, in a kind of The suitable solvent, carry out in figure I each step to the IV description.
From the phenylacetic acid ester of structural formula (III) or from the ketone ester of structural formula (VI), the step that shows by the figure I can prepare the compound of the present invention of structural formula (I).
The compound that therefore, can prepare structural formula (I) with the phenylacetic acid ester of a kind of alkali (resembling sodium hydride or sodium methoxide) and methyl formate Processing Structure formula (III).If then a kind of formula CH
3The material of L, wherein the L definition as above is added in the reactant mixture, can obtain the compound of structural formula (I).If Protic acid is added in the reactant mixture, can obtain the compound of structural formula (II), wherein R
5Be hydrogen.In addition, R
5The compound itself that is the structural formula (II) of a kind of metal (as sodium) can separate from reactant mixture.
R
5Be a kind of compound of structural formula (II) of metal, with a kind of formula CH
3The material of L, wherein the L definition is as above handled, and can be transformed into the compound of structural formula (I).R
5Be the compound of the structural formula (II) of hydrogen, with a kind of alkali (resembling potash) and a kind of general formula CH
3The material of L is handled continuously, can be transformed into the compound of structural formula (I).
In addition, under acid or alkaline condition, can prepare the compound of structural formula (I) from the acetal cancellation methyl alcohol of structural formula (IV).For the reagent of this transition energy use or the example of reagent mixture is diisopropyl amide base lithium; Potassium acid sulfate (referring to, as T Yamada, H Hagiwara and H Uda, J.Chem.Soc., Chemical Communications.1980,838, and reference wherein); And triethylamine, usually resemble in the presence of the titanium tetrachloride (for example referring to, K Nsunda and L Heresi, J.Chem.Soc., Chemical Communications, 1985,1000) in Lewis acid.
In the presence of Lewis acid (resembling titanium tetrachloride), handling R with trimethyl orthoformate is the ketenes of the structural formula (V) of the alkyl methyl alcohol first silanol that contracts, can prepare structural formula (IV) acetal (for example referring to, K Saigo, M Osaki and T Mukaiyama, Chemistry Letters, 1976,769).
With a kind of alkali and a kind of formula R
3SiCl or R
3The trialkylsilkl halide of SiBr, for example trimethylsilyl chloride is perhaps used a kind of alkali (for example triethylamine) and a kind of formula R
3Si-OSO
2CF
3Trifluoromethane sulfonic acid trialkylsilkl ester handle, the ketenes that can prepare structural formula (V) from the phenylacetic acid ester of structural formula (III) contracts methyl alcohol first silanol (for example referring to, C Ainsworth, F Chen and Y Kuo, J.Organometallic Chemistry, 1972,46,59)
Intermediate (1 V) and (V) always must not separated.Under suitable condition, by the above-mentioned suitable reagent of enumerating of continuous adding, can prepare the compound of structural formula (I) from the phenylacetic acid ester of structural formula (III) at " in the reactor ".
In addition,, for example use the ketone ester of methoxyl group methylene tri Phenylphosphine Processing Structure formula (VI), can prepare the compound of structural formula (I) with methoxyl group methylenation reagent.(for example referring to W Steglich, G Schramm, T Anke and F.Oberwinkler, EP0044448,4.7.1980).
The ketone ester that can prepare structural formula (VI) with the method for describing in the document.Useful especially method comprises that (ⅰ) uses L M Weinstock, R B Currie and A V Lovell, Synth.Commun., 1981,11 943 and its list of references, suitable phenyl-magnesiumhalide or phenyl-lithium class is reacted with dimethyl oxalate; (ⅱ) make the phenylacetic acid ester oxidation of structural formula (III) with selenium dioxide, generally do not need solvent, temperature is more than 100 ℃; (ⅲ) oxidation of mandelate for example uses manganese oxide to carry out in The suitable solvent.
The figure II shows the method that can prepare the phenylacetic acid ester of structural formula (III) from the 3-isochromanome of structural formula (IX).
Therefore, use formula R
1YM, wherein R
1With Y definition as above and M be a kind of metal (for example sodium or potassium), handle the phenylacetic acid that isochromanome (IX) obtains structural formula (VIII).By the conventional method of describing in the document, phenylacetic acid (VIII) can be transformed into phenylacetic acid ester (III).
In addition, use HZ in methyl alcohol, can make the isochromanome of structural formula (IX) be transformed into the phenylacetic acid ester of structural formula (VII), wherein Z is halogen atom (a for example bromine).If handle isochromanome (IX) with HZ in a kind of Non-alchoholic solvents, this transformation also can be finished the general step esterification of the phenylacetic acid of generation with two steps.(for example referring to, I Matsumoto and J Yoshizawa, Jpn.Kokai(Tokkyo Koho) 79 138 536,27.10.1979, Chem.Abs., 1980,92,180829h and G M F Lim, Y G Perron and R D Droghini, Res.Discl., 1979,188,672, Chem.Abs., 1980,92,128526t).Use R
1YM handles (R wherein
1, Y and M definition is as above) and the phenylacetic acid ester of structural formula (VII) can be transformed into the phenylacetic acid ester of structural formula (III).
Also can prepare the phenylacetic acid ester of structural formula (III) and the phenylacetic acid of corresponding structure formula (VIII) by many other methods of in Chemistry Literature, describing.For example, D C Atkinson, K E Godfrey, B Meek, J F Saville and M R Stillings, J.Med.Chem., 1983,26,1353 and D C Atkinson, K E Godfrey, P L Meyers, N C Phillips, M R Stillings and A P Welbourn, J.Med.Chem., 1983,26,1361, several useful method have been described.And then use J-P Rieu, and A Boucherle, H Cousse and G Mouzin, Tetrahedron, 1986,42, the 4095 many methods for preparation 2-arylprop acid esters and propionic acid description adopt suitable precursor (wherein existing substituting group (R
1Y) R
2R
3C-and X), also can be used for preparing the phenylacetic acid ester of structural formula (III) and the phenylacetic acid of structural formula (VII)
By the method for describing in the document can prepare structural formula (IX) isochromanome (for example, referring to V B Milevskaya, R V Belinskaya, with L M Yagupol ' skii.Zh.Org.Khim., 1973,9,2145; Chem.Abs., 80,36954e).
The explanation of figure III produces the method for structural formula (I) compound from the precursor that contains the 'beta '-methoxy acrylic acid methyl esters.Therefore, use formula R
1YM compound treatment, wherein R
1, Y and M definition as above, the acrylate of structural formula (X) is transformed into the compound of structural formula (I).Work as R
1Be one replace arbitrarily contain the heteroaryl of a nitrogen-atoms at least the time (for example pyridine radicals that replaces arbitrarily), formula R
1The YM compound can be an ambient nucleophile, promptly can react at the Y place again in the reaction of nitrogen place so in principle.For example, the slaine of 2 hydroxy pyrimidine promptly can also can obtain corresponding N-alkyl pyridone or 2-alkoxy pyridines product respectively in oxygen place and alkylating reagent reaction at the nitrogen place.In this case, can obtain optionally metalepsis on the Y (for example, referring to G C Hopkins, J P Jonak, H J Minnemeyer and H Tieckelmann, J.Org.Chem., 1967,32 4040) with the method that exemplifies in the document.For example, with the method for describing in N-bromo-succinimide or sulfonic acid chloride and the document, can prepare the compound of structural formula (X) by the halogenation of structural formula (XII) alkylbenzene, wherein L is a kind of halogen, and for example bromine or chlorine are (for example, referring to Modern Synthetic Reactions, Herbert House, 2nd Edition, Benjamin/Cummings, P.478 and list of references, with H.Matsumoto etc., Chemistry Letters, 1978, pp.223-226).With the method for describing in a kind of sulfonic acid halide and the document, can prepare the compound of structural formula (X) from the benzylalcohol of structural formula (XI), wherein L is a sulfonyloxy.In the presence of a kind of alkali, handle benzylalcohol,, produce a kind of benzyl halide sometimes by a kind of sulphonyl oxygen-derivative with sulfonic acid halide.This has constituted the another kind of approach that is transformed into structural formula (X) compound, and wherein L is a kind of halogen.
On the other hand, work as R
1When being a kind of enough active aryl or heteroaryl, usually in the presence of a kind of alkali (for example sodium hydride, potassium tert-butoxide or potash), from the compound and the formula R of structural formula (X III)
1The L compound can prepare the compound of structural formula (I).
Be used in show in the figure I with top paragraph in method for transformation that the figure I is described, the intermediate that can prepare structural formula (XI), (XII) and (X III) from suitable phenylacetic acid ester or benzoic ether precursor.
Some that also can carry out showing in the figure III on intermediate changes, and these intermediates contain one can be transformed into the group of 'beta '-methoxy acrylic acid carbomethoxy subsequently, rather than contains the 'beta '-methoxy acrylic acid carbomethoxy.For example, the figure IV shows that the method that use to change (X) to (I) (figure III) also can be used for a halogeno-benzene (X V) and be transformed into halogeno-benzene (X IV), uses the step described in the above-mentioned paragraph or the step halogeno-benzene (X IV) of description in the literature can then be transformed into compound (I).
When Y is NR
4The time, can utilize other approach for preparing structural formula (I) compound, this shows in the figure V.In the figure V, W can be the 'beta '-methoxy acrylic acid carbomethoxy CH of α-connection
3O.CH: C(CO
2CH
3)-, perhaps W is a group or atom, and this group or atom can be transformed into CH by the step of describing in the above-mentioned paragraph (similar to the changing condition of figure V)
3OCH: C(CO
2CH
3)-.
Thereby, use reductant, lithium aluminium hydride reduction for example, reduction of amide that can bar structure formula (X VIII) becomes structural formula, and (the X VI is R wherein
2=H) amine.Use formula R
1R
4The primary amine of NH or secondary amine (R wherein
1And R
4Definition as above), in the presence of hydrogen and a kind of hydrogenation catalyst or another kind of reductant, the carbonyls of Processing Structure formula (X VII), the amine that can be transformed into structural formula (X VI) is (referring to J March, " Advanced Organic Chemistry:Reactions, Mechanisms and Structure ", 1968, McGraw-Hill Kogakusha Ltd, the 668-670 page or leaf).
Again on the one hand, the invention provides the method for the intermediate chemicals of the compound of preparation structural formula (I) and wherein employed structural formula (II) to (VI) and structural formula (VIII).
The present invention also provides the compound of the structural formula (I g) as intermediate chemicals:
Wherein T be hydroxyl, sulfydryl, formoxyl, methylol, chloromethyl, bromomethyl, amino, carboxyl or-CH
2NHR, wherein R is alkyl or aryl (C especially
1-4Alkyl or phenyl).Particularly these compounds comprise (E)-isomer.
The present invention further provides the compound of structural formula (I h) as intermediate chemicals:
Wherein Q is chloromethyl or formoxyl.Particularly these compounds comprise (E)-isomer.
Compound of the present invention is an effective bactericide and can be in order to prevent and treat one or more following cause of diseases:
Rice blast.
Wheat leaf rust, yellow rust and other rust, leaf rust of barley, yellow rust and other rust also have other host's rust, and these hosts are coffee, pears, apple, peanut, vegetables and ornamental crops.
Powdery mildew on powdery mildew of barley and wheat (Powdery mildew) and the various host is lupulus powdery mildew, squash marble dust (as cucumber) for example, apple mildew and grape powdery mildew.
Base corruption, black mole, withered, the numb spot of spot and the poliosis of cereal.
Various other spot stripes of the brown spot of peanut and black spot and other host.For example beet, fragrant burnt, soybean and rice.
Tomato, strawberry, vegetables, grape and other host's gray mold.
Vegetables (as cucumber), rape, apple, tomato and other host's epidemic disease black spot morning.
The scab of apple (scabies scab).
The downy mildew of grape.
Other downy mildew, for example downy mildew of lettuce, soybean, tobacco, onion and its host's downy mildew and hop downy mildew and pumpkin cream mildew.
Potato and tomato late blight and vegetables, strawberry, avocado, pepper, ornamental crops, tobacco, cocoa and other host's late blight.Other leaf damping off of paddy rice Thanatephorus Cucumeris and various hosts, for example wheat and barley, vegetables, cotton and turf.
Some compound exhibits go out a kind of extracorporeal disinfecting fungi activity of wide scope.These compounds may also have activity (for example withered green mold of citrus and penicilliosis and mosaic disease, fragrant burnt anthracnose and grape blossom rot) to the various diseases behind the fruit harvest.
And then, as smut and basal stem rot, the damping off of cotton and the rice blast of paddy rice of boll rot of cotton, herbage spot blight, stinking smut (bunt of wheat, the disease that a kind of wheat seed is propagated), cereal extremely of soaking seed.
Some compounds can be to top and local moving in making fabric texture.In addition, compound can volatilize, and is enough to kill fungi on the crop effectively in gas phase.
Therefore, the invention provides mycocidal method, comprise a kind of previously defined compound of sterilization effective dose or a kind ofly contain that such compound compositions is administered on the crop, on the seed of crop or be administered to crop or seed region.
Compound also can be used as industrial bactericide (with respect to agricultural), for example is used in to prevent that bacterium from corroding timber, animal skin, leather, the aspect of especially filming.
Some compounds may show plant growth regulating activity and the ratio that can suit is for this purpose promoted the use of.
Compound can directly be used as bactericide, uses more convenient but be mixed with composition with a kind of carrier or thinner.Thereby the invention provides bactericidal composition, composition comprises a kind of previously defined compound and a kind of suitable carrier or thinner.
Compound can be used in a number of ways.For example, they can through the preparation or do not prepare on the leaf that is applied directly to crop, on the seed, or crop growing and maybe will carry on the medium of cultivating thing, perhaps with spraying, dust or use with a kind of emulsion or paste mode, perhaps compound is used as steam or as sustained-release granular formulation.Can use compound any position of crop, comprise leaf, stem, branch or root, perhaps compound is used in the soil around the root, perhaps uses on the seed before carrying kind, perhaps uses in the general soil, in paddy field water either or the hydroponic system.Compound of the present invention also can be injected in the crop or with electronic spray technique or other low capacity method and spray on crop.
" crop " speech comprises rice shoot, shrub and trees as used herein.In addition, method for disinfection of the present invention comprises prevention, protection, prevention and directly handles.
The compounds of this invention preferably is used for agricultural and gardening with the form of composition.The types of compositions of using in any example will depend on the specific purpose of reality expectation.
Composition can be pulvis or the granule that comprises the spraying usefulness of active ingredient (The compounds of this invention) and a kind of solid diluent or carrier, for example solid diluent or carrier have filler, as kaolin, bentonite, diatomite, dolomite, calcium carbonate, talcum, powdery magnesia, Fnller ' s soil, gypsum, diatomite and china clay.Such granule need not further be handled and can be suitable for being administered in the soil.With the grain ball of active principle dipping filler or the mixture of active principle and pulverous filler is made particle can both make such granule.The composition of seed dressing usefulness, in order to increase the adhesion of composition, can comprise a kind of reagent (for example a kind of mineral oil), on the other hand to seed, for the purpose of dressing seed, with an organic solvent prepare active ingredient (for example N-Methyl pyrrolidone, propane diols or dimethyl formamide).Composition also can be the form of wetting powder or the granule that can be scattered in water, comprising wetting agent or dispersant, makes composition be easy to be dispersed in the liquid.Pulvis and granule also can contain filler and suspending agent.
In a kind of organic solvent that contains a kind of wetting agent or emulsifier arbitrarily, dissolve active ingredient, then this mixture is added in the water that can contain wetting agent or emulsifier, can prepare missible oil or emulsion.Suitable organic solvent is an aromatic solvent, for example alkylbenzene and Fluhyzon, and ketone such as isophorone, cyclohexanone and methyl cyclohexanone, chlorohydrocarbon such as chlorobenzene and trichloroethanes also have alcohols such as benzylalcohol, sugar alcohol, butanols and glycol ether.
By ball milling or pearl mill solid and a kind of dispersant, and add the suspending agent that prevents the solid sedimentation, can prepare the strong suspending agent of a large amount of insoluble solids.
The composition that uses as spraying can be a kind of form of aerosol, and wherein preparation is kept at certain pressure, contains in a kind of container of propellant, and for example propellant is fluoro trichloromethane or dicholorodifluoromethane.
The compounds of this invention can be mixed and made into a kind of composition that is suitable for containing in the generation of the space of sealing this compound smog in dry state and a kind of firework mixture.
On the other hand, the form that The compounds of this invention can microcapsule formulations is used.They also can make biodegradable polymer formulations, release agent with the slow control that obtains a kind of active drug.
By means of suitable additive, for example improve the additive of medicament distribution, adhesion and the rain fastness of the crop surface of handling, various compositions can be suitable for various uses preferably.
Compound of the present invention can use (as the fertilizer of nitrogenous, potassium or phosphorus) as mixture with fertilizer.The composition that only comprises the fertiliser granulates (for example dressing mixing) that is mixed with The compounds of this invention is better.Such granule is suitable for containing the The compounds of this invention up to 25% weight most.At this, the present invention also provides a kind of Ru 2006101161, comprises The compounds of this invention or its a kind of salt or the metal complex of a kind of fertilizer and general formula (I).
The outstanding agent of wetting powder, missible oil and farming generally contains surfactant, as wetting agent, dispersant, emulsifier or suspending agent.These surfactants can be cation, anion or non-ionic surfactant.
Suitable cationic surfactant is a quaternary ammonium compound, as softex kw.Suitable anion surfactant is soap, sulfated fatty alkyl monoester salt (as lauryl sodium sulfate) and sulfonated aromatic salt (as lignosulphonates, butyl naphthalene sulfonate and the diisopropyl of neopelex, sodium, calcium or ammonium and the mixture of triisopropyl sodium naphthalene sulfonate).
Suitable non-ionic surface active agent is the condensation product of oxirane and fatty alcohol, and for example fatty alcohol is oleyl alcohol or hexadecanol, or the condensation product of oxirane and alkyl phenol, as octyl phenol or nonyl phenol and octyl cresol.Other non-ionic surface active agent is condensation product and the lecithin by partial ester, this partial ester and the oxirane of long-chain fatty acid and hexitan generation.Suitable suspending agent is hydrophilic colloid (as polyvinylpyrrolidone and sodium carboxymethylcellulose) and swelling clay such as bentonite or Attagel.
The composition that is used as aqueous dispersions or emulsion generally provides the form of concentrate, and concentrate contains a kind of a high proportion of active ingredient, dilute with water concentrate before using.These concentrates preferably can be stood long-term static depositing, and can be diluted with water to water formulation after depositing like this, and this water formulation keeps homogeneous phase in the enough time, make it to use by general spraying apparatus.Calculate by active ingredient weight, concentrate can contain nearly 95%, and 10-85% is better, for example contains 25-60%.After dilution generated water formulation, according to the purpose of the phase of giving, such preparation can contain the active ingredient of various amounts, was 0.0005% or 0.01% to 10% water formulation but can use active ingredient weight.
Composition of the present invention can contain bioactive other compound of tool.If any the compound of similar or additional bactericidal activity or compound with plant growth regulation, weeding or insecticidal activity.
The Fungicidal compounds that can exist in the present composition can be a kind ofly can kill cereal (as wheat) fringe disease, for example spot blight, head blight and stripe disease, kill the parasitic disease of grape cutting and soil and downy mildew and powdery mildew, kill the compound of apple mildew and scab etc.
Than the compound of simple general formula (I) the more activity of wide spectrum is arranged by the another kind of bactericide present composition.And then the bactericidal activity of other bactericide mutual-through type (I) compound has synergistic effect.The Fungicidal compounds example that can comprise in the present composition is a carbendazim; benomyl; thiophanate methyl; thiabendazole; furidazol; kobam; Euparen; cymoxanil oxadixyl; ofurace; metalaxyl; furalaxyl; benalaxyl; fosetyl-alluminium; the phonetic alcohol of two chlorobenzenes; procymidone different third is fixed; prothiocarb; the sterilization profit; vinclozolin; penconazolemyclobutanil; propamocarb; Ro151297; diniconazole final singling phosphorus; Milstem; Plondrel; tridemorph; triforine; the spirit of ring bacterium; triazbutyl; guazatine; 1; 1 '-imino-diacetic (1; the inferior octyl group of 8-) the triacetate salt of biguanide; buthiobate; propiconazole; Prochloraz; flutriafol; hexaconazole; (2RS; 3RS)-the 2-(4-chlorphenyl)-3-cyclopropyl-1-(1H-1; 2; the 4-triazol-1-yl) fourth-2-alcohol; (RS)-and the 1-(4-chlorphenyl)-4; 4-dimethyl-3-(1H-1; 2,4-triazol-1-yl methyl) penta-3-alcohol; fluzilazole; triadimefon; the triazole dimethanol; diclobutrazol; fenpropimorph; pyrifenox; fenpropidin chlorozolinate; IMAZALIL; methuroxam; carboxin; oxycarboxin; methfuroxam; dodemorfe; BAS 454; blasticidin-S S; kasugarnycin; Hinosan; kitazine P; cycloheximide; Rabcide; probenazole; Fujione; tricyclazole; 4-chloro-N-(cyano group (ethyoxyl) methyl) benzamide; pyroquilon; chlorbeuzthiazone; Neo-Asozin; Polyoxin; valida; mepronil; flutolanil; pencycuron; diclomezine; phenazine oxide; nickel dimethyldithiocarbamate; techlofthalam; techlofthalam; bitertanol; bupirimate etaconazole hydoxyisoxazole; streptomycin; cyprofuram; biloxazol; the quinomethionate Milcurb; 1-(2-cyano group-2-methoxyl group acetimidoyl)-the 3-ethyl carbamide; fenapanil; tolclofos-methyl; the pyroxyfur Carbatene; maneb; mancozeb; difoltan; tpn; anilazine; tmtd; captan; folpet; zineb; propineb; the sulphur powder; karathane; dichlone; chloroneb; binapacryl; between nitre phthalein isopropyl ester; dodine; the Delan; fentin hydroxide; fentinacetate; tecnazene; pcnb; botran; copper-containing compound is COPPER OXYCHLORIDE 37,5 for example; copper sulphate and bordeaux mixture and organomercurial compound.The compound of general formula (I) can mix with cover crop with soil, peat or other root mounting medium, kill the fungal disease of seed, soil or leaf.
The suitable insecticide that can sneak in the present composition comprises Aphox, Rogor, methyl-0 five nine, peace fruit sevin, Mobucin, XMc, BPMc, furans pellet, carbosulfan diazinon, fenthion, Folithion, phenthoate dimephenthoate cidial, chlopyrifos, karphos, Kayaphos, nuvacron, buprofezin, tthroproxyfen and cycloprothrin.
Plant growth regulating compound is the compound that control weeds or seed blastogenesis become or control undesired plants growth (as grass).
The suitable plant growth regulator example that share with The compounds of this invention is that gibberellin is (as GA
3, GA
4Or GA
7), auximone is (as heteroauxin, indolebutyric acid, naphthoxyacetic acid or methyl), cytokinin is (as kinetin, diphenylurea, benzimidazole, benzyl purine or benayl aminopurine), phenoxy acetic acid is (as 2,4-drips or MCPA), the benzoic acid (as phenyl triiodide formic acid) that replaces, morphactin (as Chlorflurecol), maleic acid hydrazide, glyphosate, glyphosate, the fatty alcohol of long-chain and acid, dikegulac, paclobutra-trazol, fluorine sulphur peace, Mefluidide, the quaternary ammonium that replaces He phosphonium compounds (as chloromequat, chlorphonium or mepiquatchloride), ethrel, grass prestige peace, 3,6-dichloro p-Methoxybenzoic acid methyl ester, Daminozide, asulam, abscisic acid, isopyrimol, the 1-(4-chlorphenyl)-4,6-dimethyl-2-oxygen-1,2-dihydroxy-pyridine-3-carboxylic acid (as Bromoxynil), the grass pyrazoles, benzoyl prop-ethyl 3, the 6-lontrel, fenpentezol, inabenfide, triaptnthenol and tecnazene.
Following examples explanation the present invention." ether " selects ether for use among all embodiment, uses dried over mgso solution, and decompression is concentrated solution down.Relate to and under blanket of nitrogen, to carry out, and solvent to carry out drying before using the reaction of the intermediate of water sensitive.Except as otherwise noted, otherwise with silica gel as fixing phase, carry out column chromatography analysis.In this INFRARED ABSORPTION that shows and NMR data is selectively, does not enumerate each absorption in all situations.Except as otherwise noted, otherwise use CDCl
3Solution comes record ' HNMR data.All embodiment use following dummy suffix notation.
S=is unimodal for the THF=oxolane
DMF=N, dinethylformamide d=doublet
NMR=nuclear magnetic resonnance t=triplet
The infrared m=multiplet of IR=
M.p=fusing point br=broad peak
A.i=active ingredient RH=relative moisture
CV=carries training kind GC=gas chromatography
The DMSO=dimethyl sulfoxide (DMSO)
This embodiment shows (E)-2-(2-(3-chlorobenzene oxygen methyl) phenyl)-preparation of 3-methoxy-methyl acrylate (the I compound in the table I).
At DMF(25ml) in the drips of solution of 3-chlorophenol (9.26 gram) be added at DMF(50ml) in the sodium hydride suspension that stirs of 1.44 grams in (intumescence), the mixture of generation was stirring at room 1 hour.Then at DMF(25ml) in the 2-(bromomethyl) benzonitrile (11.76 gram) is added in the reactant mixture of above-mentioned stirring.After room temperature is placed 1 hour again, reactant mixture is poured in the water, used extracted by ether.Water, dilute sodium hydroxide aqueous solution and salt water elution are got thing continuously, and be then dry and concentrate, obtain a kind of orange-brown oily 2-(3-chlorobenzene oxygen methyl) benzonitrile (13.95 gram), place post crystallization.Behind the gasoline recrystallization, a kind of fusing point of analytic sample is 56 ℃.
Raney nickel alloy (9.72 gram) is added to a kind of 2-(3-chlorobenzene oxygen methyl in 75% formic acid (150ml)) in benzonitrile (9.72 gram) solution.The mixture that generates adds Raney nickel alloy (3 gram) again 150 ℃ of heating 5 hours, continues 150 ℃ of heating 17 hours.Filter said mixture and wash the gained solid with small amount of methanol.Merging filtrate and cleaning solution, dilute with water and use extracted by ether.Water, wet chemical and salt solution wash extract continuously, and is then dry and concentrated, obtains 2-(3-chlorobenzene oxygen methyl) benzaldehyde (5.80 gram), product is a kind of yellowish-brown oil.
1HNMRδ5.51（2H，S），10.18（1H，S）ppm。Heating is at THF(6ml in the time of 100 ℃) in this crude benzol formaldehyde, the inferior alum of methyl (methylthiomethyl) (1.73 gram) and the solution of threeway B (the 40%(weight of the hydroxide benzyltrimethylammon.um in the 1.21ml(methyl alcohol))) mixture three hours.Add threeway B(2ml again), mixture heated 4 hours at 110 ℃ again.Then add threeway B(2ml again) and methyl (methylthiomethyl) sulfoxide (1.5ml), said mixture heated 6 hours at 110 ℃ again.Pour in the water after the mixture cooling and use extracted by ether.Water and salt water washing extract, drying concentrates.Calculate productive rate 7% with ether as a kind of stereoisomer (1.10 grams are from the 2-(bromomethyl) benzonitrile that the eluent chromatographic isolation obtains sulfoxide (A)), product is a kind of sticking oil.
1H NMR δ 2.18(3H, S), 2.74(3H, S), 5.04 and each 1H of 5.12(, dJ12Hz), 7.85(1H, S) PPm.
Hydrogen chloride is frothed pass through the sulfoxide (A) that (50ml) stirs in the methyl alcohol of drying (1.10 gram) solution continually and steadily, come to life until solution.The mixture cooling that generates 30 minutes is poured in the mixture of ice and water then, uses extracted by ether.Wash extract with water until neutrality, then dry and concentrate obtain thick (2-(3-chlorobenzene oxygen methyl) phenyl) methyl acetate (1.03 gram), product is a kind of yellow oil.
1H NMRδ3.67（3H，s），3.75（2H，s），5.08（2H，s）ppm。This thick acetic acid esters in DMF (1.03 gram) and methyl formate (4.26ml) mixture were added drop-wise in 10 minutes in sodium hydride is arranged in the DMF suspension of stirring of (0.16 restrains), make it to be lower than 10 ℃ (foamings) with ice-cooled.Then,, then mixture is poured in the water, used the watery hydrochloric acid acidifying, use extracted by ether stirring at room reactant mixture 30 minutes.Wash extract with water, dry, concentrate, obtain a kind of oil (1.04 gram) of yellow, potash (0.94 gram) and dimethyl suflfate are added to this yellow oil continuously at DMF(12ml) in the solution of stirring in, the mixture that generates is then poured it into and is used extracted by ether in the water stirring at room 17 hours.Wash extract with water, dry, concentrate, with 1: 1 mixture of ether and gasoline as the eluent chromatographic isolation, obtain the title compound (0.55g of this embodiment, calculate productive rate 53% from sulfoxide (A)), product is a kind of colorless solid, the clear crystal fusing point that recrystallization obtains from gasoline is 82 ℃
1H NMR：δ3.71（3H，s），3.84（3H，s），4.95（2H，s），7.59（1H，s）ppm。
This embodiment shows (E)-3-methoxyl group-2-(2-(3-phenoxy phenoxy methyl) phenyl) preparation of methyl acrylate (No. 165 compounds in the table I).
At DMF(10ml) in 3-phenoxy group phenol (1.56 gram) solution room temperature under be added drop-wise at DMF(5ml) in the suspension that stirs of sodium hydride in.After 1 hour, at DMF(10ml) in (E) 2-(2-(bromomethyl) phenyl)-3-methoxy-methyl acrylate (2.0 grams, by the method preparation of describing among the EP 0203606, just replacing azodiisobutyronitrile in bromination step as catalyzer with benzoyl peroxide) solution is added in the above-mentioned suspension, then stirring at room 2 hours.It is poured in the water with extracted by ether (3 times).Water, sodium hydrate aqueous solution (2 times) and salt solution wash the extract of merging continuously, and is dry then, concentrates, with ether and 1: 1 mixture of gasoline as the eluent chromatographic isolation, obtaining title compound (1.39 grams, 51% productive rate), is a kind of almost colourless oil.
The IR(film): 1711,1633cm
-1
1H NMR：delta 3.66（3H，s），3.79（3H，s），4.93（2H，s），6.52-6.68（3H，m），6.95-7.54（10H，m），7.56（1H，s）ppm.
This embodiment shows (E)-2-(2-(3-formyl Phenoxymethyl) phenyl)-preparation of 3-methoxy-methyl acrylate (No. 175 compounds in the table I).
Under the reaction condition of in embodiment 2, describing, at 3-hydroxy benzaldehyde, sodium hydride and (E)-2-(2-(bromomethyl) phenyl)-react between the 3-methoxy-methyl acrylate, use 1: 1 mixture of ether and gasoline as the eluent chromatographic isolation subsequently, obtain productive rate and be 66% title compound, a kind of almost colourless oil.
The IR(film): 1703,1633cm
-1
1H NMR：delta 3.72（3H，s），3.84（3H，s），5.03（1H，s），7.16-7.22（2H，m），7.30-7.48（5H，m），7.51-7.56（1H，m），7.61（1H，s），9.94（1H，s）ppm.
Embodiment 4
This embodiment shows (E)-2-(2-(3-(methylol) Phenoxymethyl) phenyl)-preparation of 3-methoxy-methyl acrylate (No. 178 compounds in the table I).
Borohydride sodium (38 milligrams) in room temperature with (the E)-2-that was added to stirring in 5 minutes (2-(3-formyl Phenoxymethyl) phenyl in batches)-3-methoxy-methyl acrylate (0.325 gram is with the method preparation of describing among the embodiment 3) solution in.After initial slight effervesce reduces, continue to stir half an hour, then mixture is poured in the water, with extracted by ether (3 times).Ether extract is collected in together, water and salt solution continuous washing, then dry, concentrate, as the eluent chromatographic isolation, obtain title compound (0.22g, productive rate 67%) with ether, be a kind of oil.
The IR(film): 3434,1708,1632cm
-1
1H NMR：delta 1.79（1H，t），3.84（3H，s），3.73（3H，s），4.64（2H，d），4.97（2H，s），6.81-6.85（1H，m），6.90-6.94（2H，m），7.16-7.27（2H，m），7.30-7.38（2H，m），7.54-7.58（1H，m），7.60（1H，s）ppm.
Embodiment 5
This embodiment shows (E)-2-(2-(3-(Phenoxymethyl) Phenoxymethyl) phenyl)-preparation of 3-methoxy-methyl acrylate (No. 186 compounds in the table I).
Mesyl chloride in carrene (1ml) (0.56 gram) solution is added drop-wise to (E)-2-(2-(3-(hydroxymethyl) Phenoxymethyl) phenyl in carrene (15ml) in 5 minutes)-3-methoxy-methyl acrylate (1.07 grams, as the method preparation of in embodiment 4, describing, but this material almost is pure, can use without chromatographic purification) and the agitating solution of triethylamine (0.56 gram) in, cooling (heat release and white precipitate) on ice bath.Reactant mixture bubble heat stirred one hour to room temperature.The analysis of this time (by thin layer and gas chromatography) illustrates has lost initial alcohol.Reactant mixture is poured in the water, extracted with ether (2 times).The ether extract that merges of water, watery hydrochloric acid, water, saturated sodium bicarbonate aqueous solution, water and salt water washing continuously, right and dry and concentrate, obtain light yellow oil (1.30 gram)
At DMF(2ml) in phenol (0.37 gram) drips of solution be added at DMF(7ml) in sodium hydride (86 milligrams) suspension of stirring in (effervesce).The mixture stirring at room that generates 2 hours.Then when stirring at DMF(5ml) in above-mentioned light yellow oil (1.30 gram) solution dropwise in 5 minutes.The mixture stirring at room that generates 1 hour.It is poured into use extracted by ether in the water.Merge ether extracted liquid, water, 2M sodium hydrate aqueous solution, water and salt water washing continuously, then dry, concentrate, use ether and 1: 1 mixture of gasoline, obtain compound (0.695 gram of title as the eluent chromatographic isolation, calculate productive rate 53% from alcohol), product is a kind of sticking oil.
The IR(film): 1709,1633cm
-1
1H NMR：delta 3.69（3H，s），3.79（3H，s），4.97（2H，s），5.02（2H，s），6.85（1H，m），6.92-7.57（12H，m），7.59（1H，s）ppm.
Embodiment 6
This embodiment shows (E)-2-(2-(3-amino-benzene oxygen methyl) phenyl)-preparation of 3-methoxy-methyl acrylate (No. 34 compounds in the table I).
Under the condition of in embodiment 2, describing, at 3-amino-phenol, sodium hydride and (E)-2-(2-(bromomethyl) phenyl)-the 3-methoxy-methyl acrylate between reaction (but after adding the bromo-compound stirred reaction mixture 1 hour), obtain the title compound of 27% productive rate as eluent by chromatographic isolation with ether subsequently, product is a kind of viscose glue.
The IR(film): 3371,3458,1703,1631cm
-1
1H NMR：delta 3.50-3.80（2H，br s），3.71（3H，s），3.81（3H，s），4.92（2H，s），6.24-6.60（3H，m），7.03（1H，t），7.16-7.19（1H，m），7.26-7.38（2H，m），7.52-7.58（1H，m），7.59（1H，s）ppm.
Embodiment 7
This embodiment shows the preparation (No. 180 compounds in the table I) of (E, E) 2-(the amino Phenoxymethyl of 2-(3-(N-benzal)) phenyl)-3-methoxy-methyl acrylate.
(the E)-2-of (5ml) in DMF (the amino Phenoxymethyl of 2-(3-) phenyl)-3-methoxy-methyl acrylate (0.32 gram, as method preparation as described in the embodiment 6) and stirring the mixture of benzaldehyde (0.13 gram) heated 30 hours at 110 ℃, make its cooling then, pour in the water with extracted by ether (3 times).The extract that merges of water and salt water washing continuously, then dry and concentrate and obtain a kind of oil.At 125 ℃/0.25mmHg, remove excessive benzaldehyde by the freeze distillation, as residue, stay title compound (0.36 gram, productive rate 86%), product is a kind of viscose glue.
The IR(film): 1708,1633cm
-1
1H NMR：delta 3.70（3H，s），3.80（3H，s），5.00（2H，s），6.78（2H，m），7.16-7.60（9H，m），7.59（1H，s），7.88（2H，m），8.43（1H，s）ppm.
Embodiment 8
This embodiment shows (E)-2-(2-(3-hydroxyphenoxy methyl) phenyl)-preparation of 3-methoxy-methyl acrylate (No. 171 compounds in the table I).
Resorcinol (1.54 gram) drips of solution of (10ml) in DMF is added in the solution that the sodium hydride (0.05 gram) of in DMF (5ml) stirs in room temperature.After one hour, (E)-2-(2-(bromomethyl) phenyl of (10ml) in DMF)-3-methoxy-methyl acrylate (1.0 gram) solution is added in the reactant mixture, then, stirred 5 hours at 70 ℃ stirring at room 4 hours.After the cooling, mixture is poured in the water, used hcl acidifying, use extracted by ether.Water washs the extract of merging fully, and is dry, concentrated, uses ether and 1: 1 mixture of gasoline as the eluent chromatographic isolation, obtains a kind of oil (0.6 gram).Dissolve this oil in ether, by the solution that extract to generate with sodium hydrate aqueous solution, these water solution extracts of acidifying and extract again with ether are finished the final purification of this oil.Dry final ether extract concentrates and obtains title compound (0.24 gram), and product is colourless oil.
1H NMR：delta 3.72（3H，s），3.83（3H，s），4.94（2H，s），5.02（1H，br s），6.37-6.53（3H，m），7.04-7.56（5H，m），7.60（1H，s）ppm.
Embodiment 9
This embodiment shows (E)-3-methoxyl group-2-(2-(3-(pyrimidine-2-base oxygen) Phenoxymethyl) phenyl) preparation of methyl acrylate (No. 214 compounds in the table I).
In room temperature (E)-2-(2-(3-hydroxyphenoxy methyl) phenyl of (5ml) in DMF)-drips of solution of 3-methoxy-methyl acrylate (0.5 gram is as the method preparation of describing in embodiment 8) is added in the suspension of stirring of sodium hydride (0.03 gram) of in DMF (5ml).After one hour, add 2-chlorine pyrimidine (0.15 gram) solution of (5ml) among the DMF, the mixture of generation makes its cooling then 80 ℃ of heating 10 hours.Cooled mixture poured into use extracted by ether in the water.Water (2 times), sodium hydrate aqueous solution (2 times) and salt solution (1 time) wash extract continuously, and is then dry and concentrated, obtains a kind of linen solid (0.085 gram).Develop solid with ether, obtain title compound (0.076 gram), a kind of white solid, fusing point 157-165 ℃.
1H NMR：delta 3.68（3H，s），3.80（3H，s），4.96（2H，s），6.76-6.87（3H，m），7.04（1H，t），7.17（1H，m），7.26-7.40（3H，m），7.56（1H，m），7.58（1H，s），8.57（2H，d）ppm.
Embodiment 10
This embodiment explanation (E)-2-(2-(pyridine-2-yloxymethyl) phenyl)-preparation (No. 67 compounds in the table I) of 3-methoxy-methyl acrylate.
1H NMR（400MHz）：delta 3.68（3H，s），3.80（3H，s），5.26（2H，s），6.74（1H，d），6.82-6.90（1H，m），7.14-7.21（1H，m），7.28-7.42（2H，m），7.49-7.63（2H，m），7.54（1H，s），8.15（1H，d）ppm.
Embodiment 11
This embodiment shows (E)-2-(2-(2,3-difluoro Phenoxymethyl) phenyl)-preparation of 3-methoxy-methyl acrylate (No. 41 compounds in the table I).
At 50 ℃, stir together with N-N-methyl-2-2-pyrrolidone N-(25ml) and lithium chloride (4.0 gram).Add (E)-2-(2-(bromomethyl) phenyl after 40 minutes)-3-methoxy-methyl acrylate (2.0 gram), stirred this mixture 1 hour at 50 ℃.Reaction mixture is poured it in the water (100ml), uses extracted by ether (2 * 75ml) then.With salt water washing extract (2 * 75ml), dry, evaporation obtains a kind of white solid (1.66 gram), and it is recrystallized from gasoline (60-80 ℃) obtains (E)-2-(2-(chloromethyl) phenyl)-3-methoxy-methyl acrylate (1.0 gram productive rate 59%).Product is a kind of white crystalline form solid, fusing point 89-91 ℃.Be mixed with (E)-2-(2-bromomethyl) phenyl)-fusing point of 3-methoxy-methyl acrylate (fusing point 88-90 ℃) is reduced to 85-88 ℃.
The IR(atoleine): 1706,1628cm
-1
1H NMR（CDCl
3）：delta 3.70（3H，s），3.83（3H，s），4.50（2H，s），7.1-7.6（4H，m），7.64（1H，s）ppm.
In room temperature, in DMF (3ml) 2,3-difluorophenol (0.25 gram) drips of solution is added in the stirred suspension of sodium hydride (0.0385 gram) of in DMF (7ml).After one hour, be added in (E)-2-(2-(chloromethyl) phenyl of (5ml) among the DMF)-solution of 3-methoxy-methyl acrylate (0.385 gram), this mixture was stirring at room 16 hours.Being warmed up to 50 ℃ stirred 4 hours again.Reactant mixture is poured into (100ml) usefulness extracted by ether (2 * 75ml) in the water.With salt water washing ether extract, drying, evaporation obtains a clean oil.As eluent, obtain title compound (123 milligram, productive rate 23%) by chromatographic purification with ether and 7: 3 mixture of gasoline (60-80 ℃), product is a kind of white crystalline form solid, fusing point 60-62 ℃.
The IR(film): 1709,1632cm
-1
1H NMR（CDCl
3）：delta 3.70（3H，s），3.83（3H，s），5.04（2H，s），6.6-7.0（3H，m），7.1-7.6（4H，m），7.60（1H，s）ppm.
Embodiment 12
This embodiment shows 2-(2-chlorophenoxy methyl) preparation of phenylacetic acid methyl esters, this is preparation (E)-2-(2-(2-chlorophenoxy methyl) phenyl)-intermediate of 3-methoxy-methyl acrylate (No. 157 compounds in the table I).
2-chlorophenol (1.30 gram) is added in potassium hydroxide (0.38 gram) solution in low amounts of water, and the mixture of generation stirred 15 minutes at 50 ℃ stirring at room one hour.3-isochromanome (1.0 gram) is added in the reactant mixture, it was heated 5 hours in an open-topped flask at 150 ℃.Add 1.3 gram 2-chlorophenols again, on flask, adorn an aerial condenser, continue heating 6 hours at 150 ℃.After the cooling, this mixture is the brown oil of thickness, and it is dissolved in the mixture of ethyl acetate and watery hydrochloric acid.The organic layer of separating mixture and water layer are with ethyl acetate extraction water layer (3 times).Wash the ethyl acetate layer (3 times) of merging with water, drying concentrates, and obtains a kind of brown oil (2.76 gram) of thickness.This oil is dissolved in (60ml) in the methyl alcohol, adds several concentrated hydrochloric acids, under refluxad heated above-mentioned solution 6 hours.Pour it in the water into solution cooling back, with extracted by ether (3 times).Water, sodium hydrate aqueous solution and salt solution wash extract continuously, and is dry then, concentrates, and obtains 2-(2-chlorophenoxy methyl) phenylacetic acid methyl esters (0.36 gram), and product is a kind of oil.
The IR(film): 1733cm
-1
1H NMR：delta 3.67（3H，s），3.80（2H，s），5.19（2H，s），6.86-7.53（8H，m）ppm.
Embodiment 13
This embodiment shows (E)-3-methoxyl group-2-(2-(N-methyl-N-phenyl-amino methyl) phenyl) preparation of methyl acrylate (No. 2 compounds in the table III).
At 80 ℃ of heating (E)-2-(2-(bromomethyl) phenyl of (20ml) in DMSO)-3-methoxy-methyl acrylate (10.0 gram purity 90%), Phosphoric acid disodium dodecahydrate (Na
2HPO
4, 5.74 grams) and orthophosphoric acid potassium dihydrogen (KH
2PO
4, 0.55 gram) mixture 1 hour, then 110 ℃ heat again one hour (JH Babler relatively, M J Coghlan, M Feng and P Fries, J, Org, Chem,, 1979,44 1716).After the cooling, reactant mixture is poured in the water, used extracted by ether.With salt water washing extract, drying, concentrate, obtain (E)-2-(2-formylphenyl with ether as the eluent chromatographic isolation)-3-methoxy-methyl acrylate (2.77 grams, productive rate 40%), product is a kind of white crystalline form solid, fusing point 67-69 ℃.
The IR(atoleine): 1710,1634cm
-1
1H NMR：delta 3.72（3H，s），3.84（3H，s），7.30-7.65（3H，m），7.69（1H，s），7.9（1H，m），10.0（1H，s）ppm.
(E)-2-(2-formylphenyl of (about 3ml) in (40-60 ℃) gasoline)-the mixture stirring at room of 3-methoxy-methyl acrylate (0.10 gram), methylphenylamine (0.27 gram) and glacial acetic acid (1ml).Add borane-pyridine complex (0.4ml) after 2 hours, the mixture of generation stirred 2 hours again.Add 5M hydrochloric acid (2ml) subsequently, when gas is overflowed fully, add sodium hydrate aqueous solution again, make reactant mixture be alkalescence.Use the extracted by ether mixture.With salt water washing extract, dry, concentrated, use gasoline and 1: 1 mixture of ether as the eluent chromatographic isolation, obtain title compound (0.08 gram), product is a kind of white crystalline form solid, fusing point 115-121 ℃, becomes aubergine through placing.
1H NMR：delta 3.01（3H，s），3.72（3H，s），3.86（3H，s），4.35（2H，s），7.54（1H，s）ppm.
Embodiment 14
This embodiment shows (E)-2-(2-(bromomethyl) phenyl)-the another kind of preparation method of 3-methoxy-methyl acrylate.
Bromine (0.25ml) is added to (the E)-3-methoxyl group-2-(2-aminomethyl phenyl of in chloroform (40ml) in room temperature) in the agitating solution of methyl acrylate (1.0 gram) and azodiisobutyronitrile (0.1 gram), shine with 100 watts of tungsten lamps simultaneously.After 3 hours, reactant mixture is poured into sodium metabisulfite (50ml 50% the aqueous solution) lining.Wash organic facies separately with water, the dry then and concentrated a kind of peace and quiet oil (1.2 gram) that obtains.As eluent, silica gel chromatography is purified, and obtains fusing point 88-90 ℃ of title compound (240 milligrams, productive rate 17%) with ether and hexane (1: 1).When having the material for preparing with the method for describing among the embodiment 2, the fusing point of mixture does not descend.
The IR(atoleine grinds): 1704,1627cm
-1
1H NMR（270MHz），delta：3.70（3H，s），3.83（3H，s），4.41（2H，s），7.1-7.6（4H，m），7.64（1H，s）ppm.
Embodiment 15
This embodiment shows (E)-2-(2-(1-(3-chlorophenoxy) ethyl) phenyl)-preparation of 3-methoxy-methyl acrylate (No. 3 compounds in the table I).
In acidifying methyl alcohol, by heating a kind of corresponding acid solution, preparation 2-ethyl benzoate methyl esters, productive rate 92%.
N-bromo-succinimide (10.7 gram) and azodiisobutyronitrile (catalytic amount) are added in the solution of the 2-ethyl benzoate methyl esters (10 gram) in carbon tetrachloride (50ml), in 80 ℃ of mixtures that add the hot reflux generation 6 hours.After the cooling, filter reaction mixture, concentrated filtrate obtain the 2-(1-bromoethyl) methyl benzoate (12 gram), to analyze by GC and NMR, product almost is pure, is a kind of oil of yellow.
1H NMR(400MHz): delta 2.05(3H, d), 3.94(3H, s), 6.31(1H, q), 7.33(1H, t), 7.55(1H, t), and 7.83(2H, significantly t) ppm.
3-chlorophenol (8.2 gram) drips of solution of (30ml) in DMF is added in the suspension that the sodium hydride (1.3 gram) of in DMF (30ml) stirs.After one hour, be added in the above-mentioned 2-(1-bromoethyl among the DMF in the time of with stirring) methyl benzoate (the thick product of 12 grams).After the stirring at room 2 hours, the mixture that generates is poured in the water, used extracted by ether.Water (2 times), sodium hydrate aqueous solution (2 times) and salt solution wash ether extract continuously, and is then dry, concentrated, obtains 2-(1-(3-chlorophenoxy) ethyl) methyl benzoate (14.84 grams, GC shows purity 88%), product is yellow oil.
1H NMR（270MHz）：delta 1.62（3H，d），3.95（3H，s），6.28（1H，q），6.67（1H，dd），6.84（2H，m），7.06（1H，t），7.30（1H，t），7.47（1H，t），7.63（1H，d），7.96（1H，d）ppm.
Above-mentioned thick 2-(1-(3-chlorophenoxy) ethyl of (50ml) in THF) methyl benzoate (14.8 gram) is added drop-wise at THF(70ml) in the solution of 0-5 ℃ of lithium aluminium hydride reduction (1.93 gram) in.Reactant mixture stirred 30 minutes about 0 ℃ subsequently, then stirring at room 2 hours.Said mixture is poured in the water carefully, used extracted by ether.Water (2 times) and salt solution wash extract continuously, dry then and concentrated 2-(1-(3-chlorophenoxy) ethyl that obtains) benzyl alcohol (11.72 grams, GC shows purity 85%) is a kind of oil of yellow.
1H NMR（400MHz）：delta 1.66（3H，d），4.76（1H，d），4.85（1H，d），5.68（1H，q）ppm.
Manganese dioxide (6.65 gram) is added in above-mentioned thick benzyl alcohol (4.02 gram) solution of in carrene (100ml), the mixture of generation added hot reflux 24 hours at 40 ℃.Filtering mixt, concentrated filtrate obtain 2-(1-(3-chlorophenoxy) ethyl) benzaldehyde (3.53 gram), this aldehyde (analyzing by GC) contains 30% benzylalcohol raw material.
The IR(film): 1691cm
-1
2 steps by the similar transformation of description in embodiment 1, crude benzol formaldehyde is converted to 2-(1-(3-chlorophenoxy) ethyl) the phenylacetic acid methyl esters, promptly in the presence of threeway B with the condensation of methyl (methylthiomethyl) sulfoxide, subsequently the sulfoxide that generates is carried out acidic methanol and decomposes.Phenylacetic acid ester (a kind of oil) passes through to use the mixture of hexane and ether (7: 3) as the eluent chromatographic purification.
The IR(film): 1739cm
-1
1H NMR（270MHz）delta：1.61（3H，d，J6.5Hz），3.70（3H，s），3.74（2H，s），5.49（1H，q，J6.5Hz），6.71（1H，dd），6.85（2H，m），7.10（1H，t，J8Hz），7.26（3H，m），7.44（1H，m）ppm.
By 2 steps of the similar transformation among the embodiment 1, the phenylacetic acid ester changes into title compound, just by handling with methyl formate and sodium hydride, handles with dimethyl suflfate and potash then.The mixture that uses ether and hexane (1: 1) is as eluent chromatographic purification title compound, and this material is an oil.
The IR(film): 1712,1634cm
-1
1H NMR（270MHz）：delta 1.50（3H，d，J7Hz），3.72（3H，br s），3.87（3H，br s），5.19（1H，br q，J7Hz），6.8（2H，m），7.1（2H，m），7.3（3H，m），7.42（1H，m），7.63（1H，s）ppm.
Be composition prepared embodiment from compound of the present invention below, these compositions are suitable for using on agricultural and the gardening.These compositions have constituted another aspect of the present invention.Percentage is by weight calculation.
Embodiment 16
Mix and the stirring following ingredients, dissolved up to all the components, make a kind of missible oil.
No. 1 compound 10% in the table I
Benzylalcohol 30%
Calcium dodecyl benzene sulfonate 5%
Ethoxylated nonylphenol (13 moles of ethylene oxide) 10%
Alkylbenzene 45%
Embodiment 17
Active ingredient is dissolved in the carrene, and this liquid of generation is sprayed on the particle of Attagel clay.Allow solvent evaporate, form granule composite.
No. 1 compound 5% in the table I
Attagel particle 95%
Embodiment 18
By grinding and mix the composition of following three kinds of compositions preparation conduct seed dressing usefulness.
No. 1 compound 50% in the table I
China clay 48%
Embodiment 19
By grinding and mixing active ingredient and talcum, prepare the pulvis of energy dusting.
No. 1 compound 5% in the table I
Talcum 95%
Embodiment 20
By the aqueous suspension of ball milling following compositions formation with the mixture of water development, preparation suspension concentrates.
No. 1 compound 40% in the table I
Sodium lignosulfonate 10%
Water 49%
This preparation dilute with water can use as spraying, perhaps directly uses on the seed.
Embodiment 21
By mix and grind following compositions together,, make wetting powder until all fully mixing.
No. 1 compound 25% in the table I
Sodium lignosulfonate 5%
Silica 25%
China clay 43%
Embodiment 22
For killing the leaf surface fungi disease of various crops, test all cpds of the present invention.Use following technology.
Crop is sowed in John Innes basin compost in the little basin of diameter 4cm (numbering 1 or 2) lining.The compound of test preparation promptly can grind with the Dispersol T aqueous solution one beading up, also can make it to become at acetone or the solution in acetone, directly is diluted with water to needed concentration before the use immediately.Prevent and treat foliage disease, preparation (100ppm active ingredient) is sprayed on the blade face and is administered to crop root in the soil.Adopt spray-on process to reach maximum delay, the final concentration of root administration simultaneously is approximately 40ppm ai/ dry ground earth.When spray-on process was used for cereal, the polysorbas20 final concentration was added to 0.05%.
In great majority tests, compound administration of the present invention (root is executed) and when being administered on the blade face (spray-on process) in soil, they are used the previous day or two days by the disease infection crop.An exception is the test of powdery mildew of wheat and barley, and is at this moment, infected preceding 24 hours crops of processing.Be sprayed at spore suspension on the leaf of trial crops and use the blade face cause of disease.After crop infects, be placed on to allow in the adapt circumstance infect and proceed.Allowing cause of disease hide simultaneously cultivates till can estimating the disease situation.According to disease and ambient conditions, the time from infecting to estimating can change 4 days to 14 days.
Write down the disease control situation in order to following grade:
4=is disease-free
Trace is to 5% disease on the unprocessed crop of 3=
6% to 25% disease on the unprocessed crop of 2=
26% to 59% disease on the unprocessed crop of 1=
60% to 100% disease on the unprocessed crop of 0=
The results are shown in the table V.
Embodiment 23
With table in the I No. 1 and No. 23 compounds peanut and tomato are done the phytotoxicity test, tomato is made phytotoxicity with No. 169 compounds in the table I and test.It is order purpose in order to contrast, in the same way, with known compound (E)-2-(2-Phenoxymethyl) phenyl-3-methoxy-methyl acrylate (in EP-A-0178826 open and be not content of the present invention) carried out the phytotoxicity test side by side.This compound is called " control compound " at this.
Test procedure is as follows.
(a) peanut
The Peanut Crop of breeding CV.Tomnut in No. 1 compost of John Innes.Under controlled environmental condition, promptly, make plant growth respectively at the illumination in 16 hours of 27 ℃/80%RH and 8 hours dark states of 20 ℃/95%RH.Select 8-10 days plant in the test without exception.
With 5cm
3DISPERSOL T
*The compound of test preparation is diluted to required concentration with deionized water, soaks into method with root and is administered to (the each processing used 10ml) on the crop.
All processing repeat 4 times.Root with deionized water saturation process contrast crop.All crops are about 27 ℃ of placements in the greenhouse.
*The mixture of sodium sulphate and formaldehyde and sodium naphthalene sulfonate condensation product.DISPERSOL T is a registration mark, belongs to Imperial Chemical Industries PLC and owns.
After handling a week, compare, crop is carried out phytotoxicity evaluating with check plant.Estimate phytotoxicity according to the lineal scale of 0-5,1=minor injury wherein, the 5=plant dies.The results are shown in the table VI.
(b) tomato
For unanimity, the following growth of the greenhouse experiment tomato plant (CV.Outdoor Girl) 20 days, that be planted in No. 1 compost of John Jnnes that is chosen in 24 ℃ is done experiment.
With test compound at 5cm
3Be processed into preparation among the DISPERSOL T, be diluted to the concentration of hope with deionized water.Under 10psib pressure, all plant surfaces are sprayed onto maximum hold-up with hand-held Devilbiss spray gun.After the chemical treatment, plant is preserved under the following conditions: following 8 hours dark of 21 ℃/60%RH illumination in following 16 hours and 18 ℃/95%RH.All processing repeat 4 times.Check plant is sprayed with deionized water.
After handling a week, the similar approach during according to above-mentioned evaluation peanut is carried out phytotoxicity evaluating to plant.
In the test of No. 169 compounds, having carried out three times and handled in comprising the table I, is 3-4 days at interval, handles later week the last time, estimates phytotoxicity.
The table VI
Test compound (a) tomato (b) peanut
300 100 30（ppm） 100（ppm）
Compound 23, table I 2.3 1.5 0.3 0.13
Control compound 3.0 3.4 2.8 1.5
The table VII
The test compound tomato
100 30 10（ppm）
Compound 169, table I 1.5 0.9 0.3
Control compound 3.4 3.4 2.8
Conclusion
The result that table VI and VII are showed shows that 1,23 and No. 169 The compounds of this invention (replacing with chlorine or lignocaine) in the I is lower than the control compound phytotoxicity that does not have accordingly to replace on Phenoxymethyl part phenyl ring.
Embodiment 24
This example shows, when various crops being carried out full crop screening test, 1,23 and No. 68 compound in the table I has plant growth regulating character.Crop species is understood in the acceptance of the bid of table VII, and indicates the leafing stage when spraying medicine.
Use a kind of crawler type sprayer and SS8004E(threeway nozzle) with 4000ppm(by 1000 liters of/hectare land for growing field crops volumes, 4 kg/ha) use the preparation of every kind of medicine.
Behind the spray medicine, make plant growth in 22 ℃ the greenhouse 25 ℃/night by day.When needing, give to replenish illumination, so that the provide 16 hours illumination period of (minimum 14 hours).
After greenhouse 2-6 week, according to kind and season, the contrast crop of spraying with blank preparation contrasts, and the order side is estimated the morphological feature of crop.The table VIII provides evaluation result.
The table VII
The crop material that is used for full crop screening
Crop per 3 " basin compost when kind code name kind is handled
The vegetative stage crop is counted type
Barley BR Atem 1-1.5 leaf 4 JIP
*
Tomato TO Ailsa Craig 2-2 1/2 leaf 1 PEAT
*John Innes basin compost
The table VIII
Crop compound number R G A T I P
Material (table I)
TO 1 3 3 1 2
TO 23 3 3 3
TO 68
BR 68 1
MZ 23
Keyword:
The R=retardation
The G=greening effect
The A=top is injured
T=is tillered or lateral branching
Between the I=tip of a leaf or length of internode reduce
The P=phytotoxicity
Except that phytotoxicity, all effects are pressed 1-3 level visual assessment, wherein
1＝10-30%
2＝31-60%
3＝61-100%
Blank expression effect is less than 10%
Press 1-5 level visual assessment phytotoxicity
1=is less than 10%
2＝11-30%
3＝31-50%
4＝51-70%
5=is greater than 70%
Any effect is not observed in blank expression.
Claims (11)
1, a kind of composition pesticide comprises formula I compound and the stereoisomer thereof of the 0.0005%-95% (weight) as active component:
Wherein,
R
1It is phenyl; Or
With one or more halogens, hydroxyl, C
1-4(it can be by halogen, hydroxyl, phenoxy group, nitro-phenoxy, C for alkyl
1-4Alkoxy carbonyl or substituted-phenyl replace, and the substituting group of this substituted-phenyl is halogen, C
1-4Alkyl or C
1-4Alkoxyl), amino, C
1-4Alkoxyl, halogen (C
1-4) alkoxyl, (it can be by halogen, C for phenyl
1-4Alkyl, C
1-4Alkoxyl, cyano group, nitro, phenoxy group or phenoxy group C
1-4Alkyl replaces), phenyl (C
2-4) thiazolinyl, (it can be by halogen C for phenoxy group
1-4Alkyl, trifluoromethyl, C
1-4Alkoxyl, phenyl, phenoxy group, replace), (it can be by nitro or CH for benzyloxy
3O
2CC: CHOCH
3Replace), pyrimidine radicals, pyridine oxygen base (it can be replaced by trifluoromethyl), 2-pyrimidinyl oxy, halogen 2-pyrimidinyl oxy, pyrimidine sulfenyl, morpholino ,-OCOR ' ,-NHCOR ' ,-COR ' ,-NR ' R " ,-COOR ' ,-OSO
2R ' ,-CH=NPh or-phenyl that N=CHPh replaces, preceding various in R ' and R " hydrogen, C respectively do for oneself
1-4(it can be by C for alkyl or phenyl
1-4Alkyl replaces) and Ph be phenyl; Or
Pyridine radicals; Or
With one or more halogens, hydroxyl, C
1-4Alkyl, C
1-4Alkoxyl, halogen (C
1-4) alkyl, C
1-4Alkoxy carbonyl-(C
1-4) alkyl, nitro, cyano group, phenyl, phenoxy group ,-OCOR ', COOR ' or NR ' R " pyridine radicals that replaces, preceding various in R ' and R " definition the same, and the cyclopropyl carbonyl aminoderivative of this substituted pyridinyl; Or
Pyrimidine radicals; Or
The trifluoromethyl pyrimidine base; Or
Quinolyl; Or
C
1-4The alkyl quinoline base; Or
Quinazolyl (it can be by COOR ' replacement, and R ' definition is the same); Or
Dibenzofuran group;
R
2And R
3Hydrogen or C respectively do for oneself
1-4Alkyl; With
Y is oxygen, sulphur or NR
4, R wherein
4Be hydrogen or C
1-4Alkyl;
Additional conditions are for as Y being oxygen and R ' when being unsubstituted phenyl, at least R
2And R
3In one neither hydrogen neither methyl;
With a kind of sterilization acceptable carrier or thinner.
2, according to the composition of claim 1, wherein active component is formula (I) compound (E)-isomer.
3, according to the composition of claim 1, wherein active component be formula (I is compound (E)-isomer a):
Wherein,
Ab is selected from the bromine by 2-, 3-iodine, the 2-ethyl, the 3-isopropyl, the 3-normal-butyl, the 3-trifluoromethoxy, 3-amino, the 4-phenyl, the 2-carboxyl, the 3-methoxycarbonyl, the 2-hydroxyl, 2, the 3-difluoro, 3, the 5-difluoro, 2, the 3-dimethoxy, 2-fluoro-4-chlorine, 2-chloro-5-fluorine, 2-fluoro-6-methyl, 3-methyl-4-fluorine, 3-fluoro-5-methoxyl group, 2-methoxyl group-3-fluorine, 2-chloro-4-methyl, the 2-methyl-5-chloro, 2-chloro-6-methoxyl group, 3-methoxyl group-4-chlorine, 3-methyl-5-methoxyl group, 2,4, the 6-trifluoro, 2,4, the 6-trichlorine, 2,4, the 6-trimethyl, 2,6-two fluoro-4-chlorine, 2,6-dimethyl-4-fluorine, 2,3,5, the 6-tetrachloro, one group of group that five fluorine and pentachloro-are formed.
4, according to the composition of claim 1, wherein active component is formula (I b) compound (E)-isomer:
Wherein,
Y is the definition that claim 1 provides, and m is that integer and the A of 1-5 is the plain hydroxyl of fontanel, C
1-4Alkyl, halogen (C
1-4) alkyl, C
1-4Alkoxyl, halogen (C
1-4) alkoxyl, phenyl, phenoxy group, nitro, amino, cyano group, carboxyl, C
1-4Alkoxy carbonyl group, C
1-4Alkyl-carbonyl oxygen base or C
1-4Alkyl-carbonyl-amino.
5, according to the composition of claim 1, wherein active component is formula (I c) compound (E)-isomer:
Wherein,
B is N or CH; Y is the definition that claim 1 provides; When B was N, P was 0 or 1, or P is 0 or the integer of 1-4 when B is CH; With when B is N, A ' is trifluoromethyl or when B is CH, A
1Be halogen, hydroxyl, C
1-4Alkyl, C
1-4Alkoxyl, trifluoromethyl, nitro, amino, cyano group, phenyl, phenoxy group, C
1-4Alkoxy carbonyl or C
1-4The alkyl-carbonyl oxygen base.
6, according to the composition of claim 5, wherein Y links the ortho position of theheterocyclic nitrogen atom, or the ortho position that substituent A is linked theheterocyclic nitrogen atom, perhaps Y and A
1All link the ortho position of theheterocyclic nitrogen atom.
7, according to the composition of claim 1, wherein active component is formula (I d) compound (E)-isomer:
Wherein, q is 0 or the integer of 1-5; D is a halogen; C
1-4Alkyl, trifluoromethyl, C
1-4Alkoxyl, trifluoromethoxy or phenoxy group; With E be hydrogen or halogen.
8, according to the composition of claim 1, wherein active component is formula (I f) compound (E)-isomer:
In the formula, A is 3-bromine, 3-chlorine or 4-chlorine.
9, preparation claim 1 method for compositions, the method comprises mixes a kind of sterilization acceptable carrier or thinner mutually with the defined formula of claim 1 (I) compound, and wherein the method for preparation formula (I) compound comprises:
(a) use formula CH
3The compound of L, wherein L is a kind of leaving group, processing formula (II) compound
In the formula, R
1, R
2, R
3With Y be the definition that claim 1 provides, R
5It is metallic atom; Or
(b) under the condition of acid or alkali, cancellation methyl alcohol from formula (IV) compound
R wherein
1, R
2, R
3With Y be the definition that claim 1 provides; Or
(c) ketone ester of usefulness methoxyl group methylenation agent treated formula (VI):
R wherein
1, R
2, R
3With Y be the definition that claim 1 provides; Or
(d) use formula R
1YM compound, wherein R
1With Y be the definition that claim 1 provides, M is a metallic atom, processing formula (X) compound:
Wherein, R
2And R
3Be the definition that claim 1 provides, L is a leaving group; Or
(e) in the presence of alkali, use formula R
1The L compound, R in the formula
1Be the definition that claim 1 provides, L is a leaving group, processing formula (X III) compound:
Wherein, R
2, R
3With Y be the definition that claim 1 provides; Or
(f) when Y be NR
4The time, R
4Be the definition that claim 1 provides, the acid amides of reduction-type (X VIII):
R wherein
1And R
4Be the definition that claim 1 provides, W is a kind of CH of being converted into
3OOCH: C(CO
2CH
3) group; Or
(g) when Y be NR
4The time, R
4The definition that provides for claim 1 is with a kind of formula R
1R
4The primary amine of NH or secondary amine, R in the formula
1, R
4The definition that provides for claim 1 and a kind of suitable reductant are handled the carbon group compound of formula (X VII);
R wherein
2The definition that provides for claim 1.
10, according to the method for claim 9, the method that wherein prepares intermediate formula (VIII) compound comprises: use formula R
1The YM compound, R in the formula
1With Y be the definition that claim 1 provides, M is a metallic atom, the isochromanome of processing formula (IX).
R wherein
2And R
3The definition that provides for claim 1.
11, the composition of claim 1 is used to kill fungi.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 88100636 CN1020391C (en) | 1987-02-09 | 1988-02-09 | Fungicides preparing process |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB878702845A GB8702845D0 (en) | 1987-02-09 | 1987-02-09 | Fungicides |
| CN 88100636 CN1020391C (en) | 1987-02-09 | 1988-02-09 | Fungicides preparing process |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1030749A CN1030749A (en) | 1989-02-01 |
| CN1020391C true CN1020391C (en) | 1993-05-05 |
Family
ID=25742411
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 88100636 Expired - Lifetime CN1020391C (en) | 1987-02-09 | 1988-02-09 | Fungicides preparing process |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1020391C (en) |
Families Citing this family (21)
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| GB9624615D0 (en) * | 1996-11-26 | 1997-01-15 | Zeneca Ltd | Chrystallisation process |
| CN1310899C (en) * | 2003-11-11 | 2007-04-18 | 沈阳化工研究院 | Benzopyrone compounds with pest killing and sterilizing activity and preparation and use |
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| CN101119972B (en) * | 2005-05-26 | 2011-04-13 | 中国中化集团公司 | Aromatic ether compounds, and preparation and usage thereof |
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| CN102550580A (en) * | 2011-12-10 | 2012-07-11 | 陕西美邦农药有限公司 | Bactericidal composition containing picoxystrobin and cymoxanil |
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| CN104478723B (en) * | 2014-12-11 | 2016-08-24 | 陕西师范大学 | Synthesis naphthalene derivative and the method for benzo-heterocycle compound |
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| CN107311857A (en) * | 2017-07-21 | 2017-11-03 | 云南农业大学 | (2 hydroxy phenyl) butyric acid of 4 hydroxyls of R 2 and its preparation and application |
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-
1988
- 1988-02-09 CN CN 88100636 patent/CN1020391C/en not_active Expired - Lifetime
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| Publication number | Publication date |
|---|---|
| CN1030749A (en) | 1989-02-01 |
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