CN1030749A - The method for preparing Fungicidal compounds - Google Patents
The method for preparing Fungicidal compounds Download PDFInfo
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- CN1030749A CN1030749A CN88100636A CN88100636A CN1030749A CN 1030749 A CN1030749 A CN 1030749A CN 88100636 A CN88100636 A CN 88100636A CN 88100636 A CN88100636 A CN 88100636A CN 1030749 A CN1030749 A CN 1030749A
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Abstract
The Fungicidal compounds and the steric isomer thereof of structural formula (I), wherein R
1It is aryl that replaces arbitrarily or the heteroaryl that replaces arbitrarily; Y is oxygen, sulphur or NR
4R
2, R
3And R
4Can be identical or different, they are hydrogen, C
1-4Alkyl or C
2-4Alkenyl; X is halogen, C
1-4Alkyl, C
2-4Alkenyl, C
1-4Alkoxyl group nitro or cyano group, and n is an integer of 0 or 1 to 4; Regulation when Y be that oxygen, n are 0 and R
1When being the phenyl that does not have to replace, R at least
2And R
3In one be not hydrogen or methyl.
Description
The invention relates to as the acrylic acid derivative of sterilant, prepare these derivatives method, contain the fungicidal composition of this analog derivative and use the germ-resistant method of this analog derivative, be particularly useful for the crop of fungi infestation.
The invention provides a kind of compound and steric isomer thereof of structure 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 group, 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 that the invention provides as defined above on the one hand, wherein y is the structure formula I of oxygen.
On the other hand, the invention provides as defined above, R wherein
1It is the compound of the structure 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 structure 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 structure 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 structure formula I of alkenyl.
Compound of the present invention contains a carbon-to-carbon double bond at least, and this sometimes compound obtains with the form of geometrical 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 section).
Another isomer fungicidal activity height of common a kind of ratios of the isomers, the isomer with high fungicidal 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 heteroatoms O, S and N or 6 yuan of heterocyclic groups (preferably heteroatoms is S or N) and thick and the benzenoid form and the fragrant type ring system of mixing.R
1Example as heteroaryl group is pyridyl, pyrimidyl, 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 allyl group), C
2-4Alkynyl group (especially propargyl), C
1-4Alkoxyl group (especially methoxyl group), C
2-4Alkenyloxy (especially allyloxy), C
2-4Alkynyloxy group (especially alkynes propoxy-), halo (C
1-4) alkyl (especially trifluoromethyl, trichloromethyl and chloro and bromomethyl), halo (C
1-4) alkoxyl group (especially trifluoromethoxy), C
1-4Alkylthio (especially methylthio group), 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 (pyridyl or the pyrimidyl that replaces especially arbitrarily) that replaces arbitrarily, the aryloxy (phenoxy group that replaces especially arbitrarily) that replaces arbitrarily, the heteroaryloxy (pyridyloxy 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 styroyl that replaces arbitrarily and the phenyl n-propyl that replaces the arbitrarily especially arbitrarily) moieties heteroaryl (C that replaces arbitrarily, replace arbitrarily with hydroxyl wherein
1-4) alkyl (especially any pyridyl or pyrimidyl (C that replaces
1-4) alkyl), the aryl (C that replaces arbitrarily
2-4) alkynyl group (especially arbitrarily replace phenylacetylene base), the heteroaryl (C that replaces arbitrarily
2-4) alkynyl group (especially arbitrarily replace pyridine acetylene or pyrimidine ethynyl), the aryl (C that replaces arbitrarily
1-4) alkoxyl group (especially arbitrarily replace benzyloxy), the heteroaryl (C that replaces arbitrarily
1-4) alkoxyl group (especially any pyridine or pyrimidyl (C that replaces
1-4) alkoxyl group), the aryloxy (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 group, C
1-4Alkylthio, 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 structure 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 group, aryloxy (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, 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 group replaces arbitrarily.
Also have on the other hand, the invention provides structure 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, 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 group 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-sec.-propyl; 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-trimethylammonium; 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 consecutive position, they can connect and form a condensed ring.This condensed ring or fragrance or aliphatic, contain one or more heteroatomss arbitrarily.Substituting group is connected to form the R of condensed ring
1Example is dibenzo-P-dioxinyl, thiophene
Base, phenoxathiinyl, dibenzofuran group and dibenzothiophene 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-withdrawing group.
Work as substituent R
2, R
3, R
4With any one of X be C
1-4Alkyl or C
1-4During alkoxyl group, 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 tertiary butyl.Other C
1-4Alkyl and C
1-4Alkoxyl group 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, allyl group ,-C(CH
3): CH
2(E) and (Z)-butenyl.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 group (especially methoxyl group), halo (C
1-4) alkoxyl group (especially trifluoromethoxy), phenyl, phenoxy group, nitro, amino, amido (especially formamido group and kharophen), cyano group, carboxyl, C
1-4Carbalkoxy (especially methoxycarbonyl) 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 or methyl ketonic oxygen base.
When m is 2 or more for a long time, substituent A m bonded example is difluoro, dichloro, dimethyl, dimethoxy, fluoro-chlorine, fluoro-2-methyl-, fluoro-methoxyl group, chloromethyl, chlorine methoxyl group, methyl methoxy base, trifluoro, trichlorine, trimethylammonium, 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 pThe bonded example is 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 group 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
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 geometrical 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=ppm
The unimodal q=quartet of s=
D=doublet m=multiplet
Table IV (continuing)
Table IV (continuing)
Table IV (continuing)
The step preparation that the compound of structure formula I of the present invention 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 leavings group such as halogenide (muriate, bromide or iodide), a kind of CH
3SO
4-negatively charged ion or a kind of sulfonyloxy-negatively charged ion, 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 structure formula III or from the ketone ester of structure formula VI, the step that shows by the figure I can prepare the compound of the present invention of structure formula I.
The compound that therefore, can prepare the structure formula I with the phenylacetic acid ester of a kind of alkali (resembling sodium hydride or sodium methylate) and methyl-formiate 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 reaction mixture, can obtain the compound of structure formula I.If Protic acid is added in the reaction mixture, can obtain the compound of structure formula II, wherein R
5Be hydrogen.In addition, R
5The compound itself that is the structure formula II of a kind of metal (as sodium) can separate from reaction mixture.
R
5Be a kind of compound of structure 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 structure formula I.R
5Be the compound of the structure formula II of hydrogen, with a kind of alkali (resembling salt of wormwood) and a kind of general formula CH
3The material of L is handled continuously, can be transformed into the compound of structure formula I.
In addition, under acid or alkaline condition, can prepare the compound of structure formula I from the acetal cancellation methyl alcohol of structure formula IV.For the reagent of this transition energy use or the example of reagent mixture is diisopropyl amide base lithium; Sal enixum (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 the structure 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 halogenide 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 structure 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 structure formula I from the phenylacetic acid ester of structure 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 structure 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 the structure 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 reference, suitable phenyl-magnesium-halide or phenyl-lithium class is reacted with dimethyl oxalate; (ⅱ) make the phenylacetic acid ester oxidation of structure formula III with tin anhydride, generally do not need solvent, temperature is more than 100 ℃; (ⅲ) oxygenizement 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 structure 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 different ketocoumaran (IX) obtains structural formula (VIII).By the general 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 structure formula III.
Also can prepare the phenylacetic acid ester of structure formula III and the phenylacetic acid of corresponding structure formula (VIII) by many other methods of in chemical 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 structure formula III and the phenylacetic acid of structural formula (VIII)
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 structure 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 structure formula I.Work as R
1Be one replace arbitrarily contain the heteroaryl of a nitrogen-atoms at least the time (for example pyridyl 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 metal-salt 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 metalepsy 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 SULPHURYL CHLORIDE and the document, the compound that can prepare structural formula (X) by the halogenation of structural formula (XII) alkylbenzene, wherein L is a kind of halogen, for example bromine or chlorine are (for example, referring to Modern Synthetic Reactions, Herbert House, 2nd Edition, Benjamin/Cummings, P.478 and reference, 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 salt of wormwood), from the compound and the formula R of structural formula (X III)
1The L compound can prepare the compound of structure 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 methoxycarbonyl subsequently, rather than contains the 'beta '-methoxy acrylic acid methoxycarbonyl.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 structure formula I compound, this shows in the figure V.In the figure V, W can be the 'beta '-methoxy acrylic acid methoxycarbonyl 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 reductive agent, lithium aluminum hydride 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 reductive agent, the carbonyl compound 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 compound of preparation structure formula I and wherein employed structure formula II method to the intermediate chemicals of (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, formyl radical, methylol, chloromethyl, brooethyl, 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 formyl radical.Particularly these compounds comprise (E)-isomer.
Compound of the present invention is an effective sterilant and can be in order to prevent and treat one or more following cause of diseases:
Rice blast.
Wheat leaf rust, stripe rust and other rust, leaf rust of barley, stripe 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 hops Powdery Mildew, squash marble dust (as cucumber) for example, apple mildew and uncinula necator.
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 black spot of apple (scabies scab).
The oidium of grape.
Other oidium, for example downy mildew of lettuce, soybean, tobacco, onion and its host's oidium 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 anthrax 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, bunt 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 be that evaporable 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 significant quantity 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 sterilant, uses more convenient but be mixed with composition with a kind of carrier or thinner.Thereby the invention provides fungicidal 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 lower volume 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 effective constituent (The compounds of this invention) and a kind of solid diluent or carrier, for example solid diluent or carrier have filler, as kaolin, wilkinite, diatomite, rhombspar, lime carbonate, talcum, powdery magnesium oxide, 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 effective constituent (for example N-Methyl pyrrolidone, propylene glycol or dimethyl formamide).Composition also can be the form of wettable powder or the granule that can be scattered in water, comprising wetting agent or dispersion agent, makes composition be easy to be dispersed in the liquid.Pulvis and granule also can contain filler and suspension agent.
In a kind of organic solvent that contains a kind of wetting agent or emulsifying agent arbitrarily, dissolve effective constituent, then this mixture is added in the water that can contain wetting agent or emulsifying agent, can prepare missible oil or emulsion.Suitable organic solvent is an aromatic solvent, for example alkylbenzene and alkylnaphthalene, and ketone such as isophorone, pimelinketone and methylcyclohexanone, hydrochloric ether such as chlorobenzene and trichloroethane also have alcohols such as benzylalcohol, sugar alcohol, butanols and glycol ether.
By ball milling or pearl mill solid and a kind of dispersion agent, and add the suspension agent that prevents solid settlement, 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 propelling agent, and for example propelling agent is fluoro trichloromethane or Refrigerant 12.
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 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, adhesive power 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 a certain salt or the metal complexes of a kind of fertilizer and logical formula I.
The outstanding agent of wettable powder, missible oil and farming generally contains tensio-active agent, as wetting agent, dispersion agent, emulsifying agent or suspension agent.These tensio-active agents can be positively charged ion, negatively charged ion or non-ionic tensio-active agent.
Suitable cats product is a quaternary ammonium compound, as cetyl trimethylammonium bromide.Suitable anion surfactant is soap, sulfated fatty alkyl monoester salt (as sodium lauryl sulphate) and sulfonated aromatic compound salt (as Sulfite lignin, butyl naphthalene sulfonate and the di-isopropyl of Sodium dodecylbenzene sulfonate, sodium, calcium or ammonium and the mixture of triisopropyl sodium naphthalene sulfonate).
Suitable nonionogenic tenside is the condensation product of oxyethane and Fatty Alcohol(C12-C14 and C12-C18), and for example Fatty Alcohol(C12-C14 and C12-C18) is oleyl alcohol or cetyl alcohol, or the condensation product of oxyethane and alkylphenol, as octyl phenol or nonyl phenol and octyl cresol.Other nonionogenic tenside is condensation product and the Yelkin TTS by partial ester, this partial ester and the oxyethane of longer chain fatty acid and hexitan generation.Suitable suspension agent is hydrophilic colloid (as polyvinylpyrrolidone and Xylo-Mucine) and swelling clay such as wilkinite or attapulgite.
The composition that is used as aqueous dispersions or emulsion generally provides the form of enriched material, and enriched material contains a kind of a high proportion of effective constituent, dilute with water enriched material before using.These enriched materials preferably can be stood long-term static depositing, and can be diluted with water to water preparation after depositing like this, and this water preparation keeps homogeneous phase in the enough time, make it to use by general spraying equipment.Calculate by effective constituent weight, enriched material can contain nearly 95%, and 10-85% is better, for example contains 25-60%.After dilution generated water preparation, according to the purpose of the phase of giving, such preparation can contain the effective constituent of various amounts, was 0.0005% or 0.01% to 10% water preparation but can use effective constituent weight.
Composition of the present invention can contain bioactive other compound of tool.If any the compound of similar or additional fungicidal 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 oidium and Powdery Mildew, kill the compound of apple mildew and black spot etc.
Than the compound of simple logical formula I the more activity of wide spectrum is arranged by the another kind of sterilant present composition.And then the fungicidal activity of other sterilant mutual-through type (I) compound has synergistic effect.The Fungicidal compounds example that can comprise in the present composition is that derosal, benomyl, thiophanate methyl, Apl-Luster, fuberidazole, Truban, Pecudin, cymoxanil oxadixyl, ofurace, metalaxyl, furalaxyl, benalaxyl, fosetyl-alluminium, the phonetic alcohol of two chlorobenzene, procymidone are different third fixed, prothiocarb, sterilization profit, Vinclozoline, penconazole
Myclobutanil; propamocarb; Ro151297; diniconazole final singling phosphorus; Milstem; ditalimfos; tridemorph; triforine; the spirit of ring bacterium; triazbutyl; guazatine; 1; 1 '-imino-diacetic (1; 8-is octylene) the triacetate salt of guanyl guanidine; buthiobate; propiconazole; Prochloraz; flutriafol; hexaconazole; (2RS; 3RS)-the 2-(4-chloro-phenyl-)-3-cyclopropyl-1-(1H-1; 2; the 4-triazol-1-yl) fourth-2-alcohol; (RS)-and the 1-(4-chloro-phenyl-)-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; miewensu S; kasugamycin; Hinosan; Kitazine P; cycloheximide; phthalide; thiabendazole; Fujione; tricyclazole; 4-chloro-N-(cyano group (oxyethyl group) methyl) benzamide; pyroquilon; chlorbeuzthiazone; Neo-Asozin; Polyoxin; validamycin; mepronil; flutolanil; pencycuron; diclomezine; phenazine oxide; nickel dimethyldithiocarbamate; techlofthalam; techlofthalam; bitertanol; bupirimate etaconazole hydoxyisoxazole; Streptomycin sulphate; cyprofuram; biloxazol; the quinomethionate Milcurb; 1-(2-cyano group-2-methoxyl group acetimidoyl)-the 3-ethyl carbamide; fenapanil; tolclofos-methyl; the pyroxyfur Carbatene; maneb; zinc manganese ethylenebisdithiocarbamate; Difolatan; m-tetrachlorophthalodinitrile; anilazine; thiram; Vancide 89; Phaltan; zineb; propineb; the sulphur powder; dinocap; dichlone; chloroneb; Niagara 9044; between nitre phthalein isopropyl ester; dodine; the Delan; fentin hydroxide; fentinacetate; tecnazene; quintozene; dicloran; copper-containing compound is COPPER OXYCHLORIDE 37,5 for example; copper sulfate and Bordeaux mixture and organomercury compound.The compound of logical formula I can mix with soil, peat or other root mounting medium with cover crop, the fungal disease of seed, soil or leaf extremely.
The suitable sterilant that can sneak in the present composition comprises Aphox, Rogor, methyl-0 five nine, peace fruit SevinCarbaryl, isoprocarb, XMc, BPMc, furans pellet, carbosulfan diazinon, fenthion, Sumithion, Tsidial, Chlorpyrifos 94, karphos, Kayaphos, monocrotophos, 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 Plant hormones regulators,gibberellins is (as GA
3, GA
4Or GA
7), plant hormone is (as indolylacetic acid, indolebutyric acid, naphthoxy acetic acid or naphthylacetic acid), cytokinin is (as kinetin, sym-diphenylurea, benzoglyoxaline, benzyl purine or benzyladenine), phenoxy acetic acid is (as 2,4-drips or MCPA), the phenylformic acid (as phenyl triiodide formic acid) that replaces, morphactin (as Chlorflurecol), Regulox, glyphosate, glyphosate, the Fatty Alcohol(C12-C14 and C12-C18) 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, succinic acid 2,2-dimethylhydrazide, asulam, dormin, isopyrimol, the 1-(4-chloro-phenyl-)-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 nitrogen atmosphere, 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 stationary 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=tetrahydrofuran (THF)
DMF=N, dinethylformamide d=doublet
NMR=nucleus magnetic resonance t=triplet
The infrared m=multiplet of IR=
M.p=fusing point br=broad peak
A.i=effective constituent RH=relative humidity
CV=carries training kind GC=vapor-phase chromatography
The DMSO=dimethyl sulfoxide (DMSO)
Embodiment 1
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-(brooethyl) benzonitrile (11.76 gram) is added in the reaction mixture of above-mentioned stirring.After room temperature is placed 1 hour again, reaction mixture is poured in the water, used ether extraction.Water, dilute sodium hydroxide aqueous solution and salt water elution are got thing continuously, and after drying 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 nickelalloy (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 washings, dilute with water and use ether extraction.Water, wet chemical and salt solution wash extract continuously, and after drying and concentrated obtains 2-(3-chlorobenzene oxygen methyl) phenyl aldehyde (5.80 gram), product is a kind of tawny 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 was 110 ℃ of reheat 4 hours.Then add threeway B(2ml again) and methyl (methylthiomethyl) sulfoxide (1.5ml), said mixture was 110 ℃ of reheat 6 hours.Pour in the water after the mixture cooling and use ether extraction.Water and salt water washing extract, drying concentrates.Calculate productive rate 7% with ether as a kind of steric isomer (1.10 grams are from the 2-(brooethyl) benzonitrile that the elutriant chromatographic separation 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.
Hydrogenchloride is frothed pass through the sulfoxide (A) that (50ml) stirs in exsiccant methyl alcohol (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 ether extraction.Wash extract with water until neutrality, and after drying 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 ester in DMF (1.03 gram) and methyl-formiate (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 dilute hydrochloric acid acidifying, use ether extraction stirring at room reaction mixture 30 minutes.Wash extract with water, dry, concentrate, obtain a kind of xanchromatic oil (1.04 gram), salt of wormwood (0.94 gram) and methyl-sulfate 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 ether extraction in the water stirring at room 17 hours.Wash extract with water, dry, concentrate, with 1: 1 mixture of ether and gasoline as the elutriant chromatographic separation, 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。
Embodiment 2
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-(brooethyl) phenyl)-3-methoxy-methyl acrylate (2.0 grams, by the method preparation of describing among the EP 0203606, just replacing Diisopropyl azodicarboxylate 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 ether extraction (3 times).Water, aqueous sodium hydroxide 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 elutriant chromatographic separation, 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.
Embodiment 3
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 conditions of in embodiment 2, describing, at 3-hydroxy benzaldehyde, sodium hydride and (E)-2-(2-(brooethyl) phenyl)-react between the 3-methoxy-methyl acrylate, use 1: 1 mixture of ether and gasoline as the elutriant chromatographic separation 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).
Sodium borohydride (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 ether extraction (3 times).Ether extract is collected in together, and water and salt solution continuous washing, and after drying concentrate, and as the elutriant chromatographic separation, obtain title compound (0.22g, productive rate 67%) with ether, are 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).
Methylsulfonyl chloride in methylene dichloride (1ml) (0.56 gram) solution is added drop-wise to (E)-2-(2-(3-(hydroxymethyl) Phenoxymethyl) phenyl in methylene dichloride (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 stirred solution of triethylamine (0.56 gram) in, cooling (heat release and white precipitate) on ice bath.Reaction mixture bubble heat stirred one hour to room temperature.The analysis of this time (by thin layer and vapor-phase chromatography) illustrates has lost initial alcohol.Reaction mixture is poured in the water, extracted with ether (2 times).The ether extract that merges of water, dilute 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 ether extraction in the water.Merge ether extracted liquid, water, 2M aqueous sodium hydroxide solution, water and salt water washing continuously, and after drying, concentrate, use ether and 1: 1 mixture of gasoline, obtain compound (0.695 gram of title as the elutriant chromatographic separation, 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-(brooethyl) 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 elutriant by chromatographic separation 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-benzylidene)) 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 phenyl aldehyde (0.13 gram) heated 30 hours at 110 ℃, make its cooling then, pour in the water with ether extraction (3 times).The extract that merges of water and salt water washing continuously, and after drying and concentrate and obtain a kind of oil.At 125 ℃/0.25mmHg, remove excessive phenyl aldehyde 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-(brooethyl) phenyl of (10ml) in DMF)-3-methoxy-methyl acrylate (1.0 gram) solution is added in the reaction 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 ether extraction.Water washs the extract of merging fully, and is dry, concentrated, uses ether and 1: 1 mixture of gasoline as the elutriant chromatographic separation, obtains a kind of oil (0.6 gram).Dissolve this oil in ether, by the solution that extract to generate with aqueous sodium hydroxide 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-chloropyrimide (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 ether extraction in the water.Water (2 times), aqueous sodium hydroxide solution (2 times) and salt solution (1 time) wash extract continuously, and after drying 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.
Suspension 2 hydroxy pyrimidine in exsiccant normal hexane (10ml) (0.50 gram) and (E)-2-(2-(brooethyl) phenyl)-3-methoxy-methyl acrylate (2.25 restrain), add silver carbonate (0.73 gram), stir the mixture and reflux 2 hours in the dark.Concentrate the mixture that cooled off and use the dichloromethane extraction residue.Filter extract by Hyflosupercel, with saturated sodium bicarbonate aqueous solution and water wash continuously, dry then, concentrate, with ether and 2: 1 mixture chromatographic separation of gasoline, obtain the compound of title, be a kind of colourless oil, leave standstill post crystallization (0.80 gram calculates productive rate 51% from 2 hydroxy pyrimidine).Recrystallization through gasoline obtains a kind of white powder, fusing point 65-66 ℃.
1H NMR（400 MHz）：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-(brooethyl) 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 ether extraction (2 * 75ml) then.With salt water washing extract (2 * 75ml), dry, evaporation obtains a kind of white solid (1.66 gram), and its recrystallization from gasoline (60-80 ℃) is obtained (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-brooethyl) phenyl)-fusing point of 3-methoxy-methyl acrylate (fusing point 88-90 ℃) is reduced to 85-88 ℃.
The IR(whiteruss): 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.Be warmed up to 50 ℃ of restir 4 hours.Reaction mixture is poured into (100ml) usefulness ether extraction (2 * 75ml) in the water.With salt water washing ether extract, drying, evaporation obtains a clean oil.As elutriant, 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 less 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 reaction mixture, it was heated 5 hours in an open-topped flask at 150 ℃.Add 1.3 gram 2-chlorophenols again, on flask, adorn an atmospheric condenser, continue heating 6 hours at 150 ℃.After the cooling, this mixture is the heavy-gravity brown oil, and it is dissolved in the mixture of ethyl acetate and dilute 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 heavy-gravity brown oil (2.76 gram).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 ether extraction (3 times).Water, aqueous sodium hydroxide 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-(brooethyl) 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 ortho-phosphoric acid potassium dihydrogen (KH
2PO
4, 0.55 gram) mixture 1 hour, then 110 ℃ of reheat one hour (J H Babler relatively, M J Coghlan, M Feng and P Fries, J, Org, Chem,, 1979,44 1716).After the cooling, reaction mixture is poured in the water, used ether extraction.With salt water washing extract, drying, concentrate, obtain (E)-2-(2-formylphenyl with ether as the elutriant chromatographic separation)-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(whiteruss): 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 restir of generation 2 hours.Add 5M hydrochloric acid (2ml) subsequently, when gas is overflowed fully, add aqueous sodium hydroxide solution again, make reaction mixture be alkalescence.Use the ether extraction mixture.With salt water washing extract, dry, concentrated, use gasoline and 1: 1 mixture of ether as the elutriant chromatographic separation, obtain title compound (0.08 gram), product is a kind of white crystalline form solid, fusing point 115-121 ℃, becomes red-purple 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-(brooethyl) 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 stirred solution of methyl acrylate (1.0 gram) and Diisopropyl azodicarboxylate (0.1 gram), shine with 100 watts of tungsten lamps simultaneously.After 3 hours, reaction mixture is poured into sodium metabisulfite (50ml 50% the aqueous solution) lining.Wash organic phase separately with water, the dry then and concentrated a kind of peace and quiet oil (1.2 gram) that obtains.As elutriant, 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(whiteruss 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 Diisopropyl azodicarboxylate (catalytic amount) are added in the solution of the 2-ethyl benzoate methyl esters (10 gram) in tetracol phenixin (50ml), in the mixture of 80 ℃ of reflux generations 6 hours.After the cooling, filter reaction mixture, concentrated filtrate obtain the 2-(1-bromotrifluoromethane) methyl benzoate (12 gram), to analyze by GC and NMR, product almost is purified, is a kind of yellow oil.
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-bromotrifluoromethane 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 ether extraction.Water (2 times), aqueous sodium hydroxide solution (2 times) and salt solution wash ether extract continuously, and after drying, concentrated obtains 2-(1-(3-chlorophenoxy) ethyl) methyl benzoate (14.84 grams, GC shows purity 88%), product is an xanchromatic 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 aluminum hydride (1.93 gram) in.Reaction mixture stirred 30 minutes about 0 ℃ subsequently, then stirring at room 2 hours.Said mixture is poured in the water carefully, used ether extraction.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 xanchromatic oil.
1H NMR（400MHz）：delta 1.66（3H，d），4.76（1H，d），4.85（1H，d），5.68（1H，q）ppm.
Manganse Dioxide (6.65 gram) is added in above-mentioned thick benzyl alcohol (4.02 gram) solution of in methylene dichloride (100ml), the mixture of generation was 40 ℃ of reflux 24 hours.Filtering mixt, concentrated filtrate obtain 2-(1-(3-chlorophenoxy) ethyl) phenyl aldehyde (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 elutriant chromatographic purification.
The IR(film): 1739cm
-1
1H NMR（270MHz）delta：1.61（3H，d，J 6.5Hz），3.70（3H，s），3.74（2H，s），5.49（1H，q，J 6.5Hz），6.71（1H，dd），6.85（2H，m），7.10（1H，t，J 8Hz），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-formiate and sodium hydride, handles with methyl-sulfate and salt of wormwood then.The mixture that uses ether and hexane (1: 1) is as elutriant chromatographic purification title compound, and this material is an oil.
The IR(film): 1712,1634cm
-1
1H NMR（270MHz）：delta 1.50（3H，d，J 7Hz），3.72（3H，br s），3.87（3H，br s），5.19（1H，br q，J 7Hz），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 ratio 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 dodecylbenzene sulphonate 5%
Ethoxylized nonylphenol (13 moles of ethylene oxide) 10%
Alkylbenzene 45%
Embodiment 17
Effective constituent is dissolved in the methylene dichloride, and this liquid of generation is sprayed on the particle of attapulgite clay.Allow solvent evaporation, form granule composite.
No. 1 compound 5% in the table I
Attapulgite 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
Mineral oil 2%
China clay 48%
Embodiment 19
By grinding and mixing effective constituent 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%
Wilkinite 1%
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 wettable powder until whole thorough mixing.
No. 1 compound 25% in the table I
Sodium lauryl sulphate 2%
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 effective constituent) is sprayed on the blade face and is administered to crop root in the soil.Adopt spray method to reach maximum delay, the final concentration of root administration simultaneously is approximately 40ppm ai/ dry ground earth.When spray method was used for cereal, the polysorbas20 final concn 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 method) in soil, they are used the day before yesterday or two days by the disease infection crop.An exception is the test of powdery mildew of cereals, 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.
Testing sequence is as follows.
(a) peanut
The Peanut Crop of breeding CV.Tomnut in John Innes1 compost.Under controlled envrionment conditions, 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 sulfate and formaldehyde and sodium naphthalene sulfonate condenses.DISPERSOL T is a registered trademark, belongs to Imperial Chemical Industries PLC and owns.
After handling a week, compare, crop is carried out phytotoxicity evaluating with control plant.Estimate phytotoxicity according to the linear 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 the John Jnnes1 compost 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.Control 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
The table VII
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 diethylin) 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 shaker 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 track type atomizer 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 photoperiod 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 specificity of crop.The table VIII provides evaluation result.
The table VII
The crop material that is used for full crop screening
*John Innes basin compost
The table VIII
Keyword:
The R=retardation
The G=greening effect
The A=top is injured
T=is tillered or lateral ramification
Between the I=tip of a leaf or panel length 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 (24)
1, the compound and the steric isomer thereof of a kind of structural formula (I), wherein R
1Be to appoint
Aryl that meaning replaces or the heteroaryl that replaces arbitrarily; Y is oxygen, sulphur or NR
4R
2, R
3And R
4Can be identical or different, they are hydrogen, C
1-4Alkyl or C
2-4Alkenyl; X is halogen, C
1-4Alkyl, C
2-4Alkenyl, C
1-4Alkoxyl group, nitro or cyano group, and n is an integer of 0 or 1 to 4; Regulation when y be that oxygen, n are 0 and R
1When being the phenyl that does not have to replace, R at least
2And R
3In one be not hydrogen or methyl.
2, according to a kind of compound of claim 1, wherein y is an oxygen.
3, according to a kind of compound of claim 1, wherein y is oxygen and R
1It is the phenyl that replaces.
4, according to a kind of compound of claim 1 or 2, R wherein
1It is the heteroaryl that replaces arbitrarily.
5, according to a kind of compound of claim 1, R wherein
1Be that aryl and the y that replaces arbitrarily is NR
4
6, according to a kind of compound of claim 1, wherein y is NR
4, and R
1Replace with a kind of electron-withdrawing group.
7, according to a kind of compound of claim 1, R wherein
1Be that aryl, the y that replaces arbitrarily is oxygen or sulphur and R
2And R
3Not hydrogen entirely.
8, according to a kind of compound of claim 1, wherein X is C
2-4Alkenyl.
9, according to a kind of compound of claim 1 or 2, R wherein
1Be with one or more hydroxyls, C
3-6Cycloalkyl (C
1-4) alkyl, aryl (C
1-4) alkoxyl group, fragrant oxygen (C
1-4) aryl that alkyl, acyloxy, CR '=NR " or N=CR ' R " replace arbitrarily, R ' and R " are respectively hydrogen, C
1-4Alkylthio, C
3-6Cycloalkyl, C
3-6Cycloalkyl (C
1-4) alkyl, phenyl or benzyl, phenyl and benzyl are at random used halogen, C
1-4Alkyl or C
1-4Alkoxyl group replaces.
10, according to a kind of compound of claim 1 or 2, R wherein
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 " is hydrogen, C
1-4Alkylthio, C
3-6Cycloalkyl, C
3-6Cycloalkyl (C
1-4) alkyl, phenyl or benzyl, phenyl and benzyl are used halogen, C arbitrarily
1-4Alkyl or C
1-4Alkoxyl group replaces.
11, a kind of structural formula ((E) isomer of I compound a)
Wherein Ab is selected from the 2-bromine, 3-iodine, the 2-ethyl, the 3-sec.-propyl, 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-trimethylammonium, 2, the 6-difluoro, 4-chlorine, 2,6-dimethyl-4-fluorine, 2,3,5, the 6-tetrachloro, five fluorine and pentachloro-group.
12, (E) isomer of the compound of a kind of structural formula (I b)
The have the right implication that provides in the requirement 1 of y wherein, m is that one 1 to 5 integer and A is halogen, hydroxyl, C
1-4 alkyl, halo (C
1-4) alkyl, C
1-4Alkoxyl group, halo (C
1-4) alkoxyl group, phenyl, phenoxy group, nitro, amino, amido, cyano group, carboxyl, C
1-4Carbalkoxy or C
1-4Alkyl carbon acyloxy.
13, the compound of a kind of structural formula (I c)
Wherein B is N or CH, the have the right implication that provides in the requirement 1 of y, and P is O or one 's 1 to 3 integer (when B is N) P or O or one 's 1 to 4 a integer (when B is CH); And A
1The implication of in claim 12 A being determined is arranged.
14, according to a kind of compound of claim 13, wherein y links the ortho position of theheterocyclic nitrogen atom, perhaps a substituent A
1Link the ortho position of theheterocyclic nitrogen atom, perhaps y and A
1All link the ortho position of theheterocyclic nitrogen atom.
15, (E) isomer of the compound of structural formula (I d)
Wherein q is O or one 's 1 to 5 a integer, and D is halogen, hydroxyl, C
1-4Alkyl, halo (C
1-4) alkyl, C
1-4Alkoxyl group, halo (C
1-4) alkoxyl group or phenoxy group and E be hydrogen or halogen.
16, (E) isomer of the compound of structural formula (I e):
Wherein B is N or CH; When B was N, r was O or one 's 1 to 3 a integer, and when B was CH, r was O or one 's 1 to 4 a integer, and D and E such as claim 15 definition.
17, (E) isomer of the compound of structural formula (I f):
Wherein A is 3-bromine, 3-chlorine or 4-chlorine.
18, according to a kind of preparation method of the compound of claim 1, it comprises:
(a) use formula CH
3The compound of a kind of compound treatment structure formula II of L:
Perhaps
(b) under acid or alkali condition, cancellation methyl alcohol from a kind of compound of structure formula IV:
Perhaps
(c) ketone ester of a kind of structure formula VI of usefulness methoxyl group methylenation agent treated:
Perhaps
(d) compound of a kind of structural formula of a kind of compound treatment (X) of usefulness formula R ' yM:
Perhaps
(e) in the presence of a kind of alkali, use a kind of R
1The compound of a kind of structural formula of L compound treatment (X III):
Perhaps
(f) when y be NR
4The time, reduce the acid amides of a kind of structural formula (X VIII):
Perhaps use a kind of formula R
1R
4The carbonyl compound of the primary amine of NH or secondary amine and a kind of suitable reductive agent Processing Structure formula (X VII):
R wherein
1, R
2, R
3, R
4, y, X and n have the implication that provides, R in claim 1
5With M be atoms metal, L is a kind of leavings group, and W a kind ofly can be transformed into CH
3OOCH:C(CO
2CH
3) group.
19, as defined the structure formula II to the midbody compound of (VI) and (VIII).
20, the compound of a kind of structural formula (I g)
Wherein T be hydroxyl, sulfydryl, formyl radical, methylol, chloromethyl, brooethyl, amino, carboxyl or-CH
2NHR, wherein R is hydrogen, alkyl or aryl.
21, the compound of a kind of structural formula (I h):
Wherein Q is chloromethyl or formyl radical.
22, according to the preparation method of the midbody compound (VIII) of claim 19, wherein use a kind of formula R
1The isochromanome of yM compound treatment structural formula (IX),
R wherein
1, R
2, R
3, the implication and the M that provide in claim 1 are arranged is a kind of atoms metal for y, X and n.
23, a kind of fungicidal composition comprises in the claim 1 to 19 of sterilization significant quantity acceptable carrier or attenuant on any compound and a kind of sterilization.
24, a kind of germ-resistant method comprises that a kind of composition with any compound in the claim 1 to 17 or claim 23 is administered to crop, crop seed or crop or seed region.
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 true CN1030749A (en) | 1989-02-01 |
| CN1020391C CN1020391C (en) | 1993-05-05 |
Family
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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 |
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| Country | Link |
|---|---|
| CN (1) | CN1020391C (en) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1091623C (en) * | 1996-11-26 | 2002-10-02 | 曾尼卡有限公司 | Crystallisation process |
| CN1092181C (en) * | 1996-06-06 | 2002-10-09 | 陶氏益农有限责任公司 | Benzyloxy substitutedaromatics and their use as fungicides and insecticides |
| WO2006125370A1 (en) * | 2005-05-26 | 2006-11-30 | Sinochem Corporation | Aromatic ether compounds,preparation and usage thereof |
| WO2007000098A1 (en) * | 2005-06-28 | 2007-01-04 | Sinochem Corporation | SUBSTITUTED p-TRIFLUOROMETHYL PHENYLETHERS, THE PREPARATIO AND THE USE THEREOF |
| CN1305858C (en) * | 2004-02-20 | 2007-03-21 | 沈阳化工研究院 | Substituted azole compounds and their preparation and application |
| 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 |
| CN101119972B (en) * | 2005-05-26 | 2011-04-13 | 中国中化集团公司 | Aromatic ether compounds, and preparation and usage thereof |
| CN102197820A (en) * | 2011-04-08 | 2011-09-28 | 陕西汤普森生物科技有限公司 | Bactericidal composition containing picoxystrobin and benzimidazoles |
| CN102204544A (en) * | 2011-04-23 | 2011-10-05 | 陕西汤普森生物科技有限公司 | Picoxystrobin-containing synergic bactericidal composition |
| CN102239863A (en) * | 2011-04-02 | 2011-11-16 | 陕西汤普森生物科技有限公司 | Bactericidal composition containing picoxystrobin and thiocarbamates |
| CN102510854A (en) * | 2010-04-21 | 2012-06-20 | 奥斯考泰克公司 | Alpha-arylmethoxyacrylate derivative, preparation method thereof, and pharmaceutical composition containing same |
| CN102550580A (en) * | 2011-12-10 | 2012-07-11 | 陕西美邦农药有限公司 | Bactericidal composition containing picoxystrobin and cymoxanil |
| CN103461368A (en) * | 2013-09-12 | 2013-12-25 | 江苏省绿盾植保农药实验有限公司 | Bactericidal composition containing picoxystrobin and prochloraz and application of bactericidal composition |
| CN104151233A (en) * | 2014-08-25 | 2014-11-19 | 浙江泰达作物科技有限公司 | Preparation method of agricultural bactericide |
| CN104230794A (en) * | 2014-08-25 | 2014-12-24 | 浙江泰达作物科技有限公司 | Method for synthesizing high-efficiency green agriculture bactericide |
| CN104478723A (en) * | 2014-12-11 | 2015-04-01 | 陕西师范大学 | Method for synthesizing naphthalene derivative and benzo-heterocycle compounds |
| CN104472490A (en) * | 2014-12-03 | 2015-04-01 | 广东中迅农科股份有限公司 | Bactericidal composition containing picoxystrobin and bromothalonil |
| 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 |
| CN108610283A (en) * | 2016-12-12 | 2018-10-02 | 沈阳中化农药化工研发有限公司 | A kind of secondary-amine compound and its preparation and application |
| CN109627211A (en) * | 2018-12-24 | 2019-04-16 | 合肥利夫生物科技有限公司 | The method that one kettle way prepares ZEN 90160 |
| CN115279185A (en) * | 2020-02-28 | 2022-11-01 | 瑞士康特股份有限公司 | Micelle disinfectant |
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1988
- 1988-02-09 CN CN 88100636 patent/CN1020391C/en not_active Expired - Lifetime
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1092181C (en) * | 1996-06-06 | 2002-10-09 | 陶氏益农有限责任公司 | Benzyloxy substitutedaromatics and their use as fungicides and insecticides |
| CN1091623C (en) * | 1996-11-26 | 2002-10-02 | 曾尼卡有限公司 | Crystallisation 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 |
| CN1305858C (en) * | 2004-02-20 | 2007-03-21 | 沈阳化工研究院 | Substituted azole compounds and their preparation and application |
| WO2006125370A1 (en) * | 2005-05-26 | 2006-11-30 | Sinochem Corporation | Aromatic ether compounds,preparation and usage thereof |
| US7786045B2 (en) | 2005-05-26 | 2010-08-31 | Sinochem Corporation | Aryl ether compounds and their preparation and use thereof |
| CN101119972B (en) * | 2005-05-26 | 2011-04-13 | 中国中化集团公司 | Aromatic ether compounds, and preparation and usage thereof |
| WO2007000098A1 (en) * | 2005-06-28 | 2007-01-04 | Sinochem Corporation | SUBSTITUTED p-TRIFLUOROMETHYL PHENYLETHERS, THE PREPARATIO AND THE USE THEREOF |
| CN100443463C (en) * | 2005-06-28 | 2008-12-17 | 沈阳化工研究院 | Substituted p-trifluoromethyl phenyl ether compound and its prepn and application |
| CN101119961B (en) * | 2005-06-28 | 2010-05-19 | 中国中化集团公司 | Substituted P-trifluoromethyl phenylethers, the preparatio and the use thereof |
| CN102510854A (en) * | 2010-04-21 | 2012-06-20 | 奥斯考泰克公司 | Alpha-arylmethoxyacrylate derivative, preparation method thereof, and pharmaceutical composition containing same |
| CN102239863A (en) * | 2011-04-02 | 2011-11-16 | 陕西汤普森生物科技有限公司 | Bactericidal composition containing picoxystrobin and thiocarbamates |
| CN102239863B (en) * | 2011-04-02 | 2013-11-06 | 陕西汤普森生物科技有限公司 | Bactericidal composition containing picoxystrobin and thiocarbamates |
| CN102197820A (en) * | 2011-04-08 | 2011-09-28 | 陕西汤普森生物科技有限公司 | Bactericidal composition containing picoxystrobin and benzimidazoles |
| CN102204544A (en) * | 2011-04-23 | 2011-10-05 | 陕西汤普森生物科技有限公司 | Picoxystrobin-containing synergic bactericidal composition |
| CN102550580A (en) * | 2011-12-10 | 2012-07-11 | 陕西美邦农药有限公司 | Bactericidal composition containing picoxystrobin and cymoxanil |
| CN103461368A (en) * | 2013-09-12 | 2013-12-25 | 江苏省绿盾植保农药实验有限公司 | Bactericidal composition containing picoxystrobin and prochloraz and application of bactericidal composition |
| CN104230794A (en) * | 2014-08-25 | 2014-12-24 | 浙江泰达作物科技有限公司 | Method for synthesizing high-efficiency green agriculture bactericide |
| CN104151233A (en) * | 2014-08-25 | 2014-11-19 | 浙江泰达作物科技有限公司 | Preparation method of agricultural bactericide |
| CN104472490A (en) * | 2014-12-03 | 2015-04-01 | 广东中迅农科股份有限公司 | Bactericidal composition containing picoxystrobin and bromothalonil |
| CN104472490B (en) * | 2014-12-03 | 2017-12-12 | 广东中迅农科股份有限公司 | A kind of bactericidal composition containing ZEN 90160 and bromothalonil |
| CN104478723A (en) * | 2014-12-11 | 2015-04-01 | 陕西师范大学 | Method for synthesizing naphthalene derivative and benzo-heterocycle compounds |
| CN104478723B (en) * | 2014-12-11 | 2016-08-24 | 陕西师范大学 | Synthesis naphthalene derivative and the method for benzo-heterocycle compound |
| CN108610283A (en) * | 2016-12-12 | 2018-10-02 | 沈阳中化农药化工研发有限公司 | A kind of secondary-amine compound and its preparation and application |
| 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 |
| CN109627211A (en) * | 2018-12-24 | 2019-04-16 | 合肥利夫生物科技有限公司 | The method that one kettle way prepares ZEN 90160 |
| CN115279185A (en) * | 2020-02-28 | 2022-11-01 | 瑞士康特股份有限公司 | Micelle disinfectant |
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| Publication number | Publication date |
|---|---|
| CN1020391C (en) | 1993-05-05 |
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