CN1021009C - Fungicides - Google Patents

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CN1021009C
CN1021009C CN 88107270 CN88107270A CN1021009C CN 1021009 C CN1021009 C CN 1021009C CN 88107270 CN88107270 CN 88107270 CN 88107270 A CN88107270 A CN 88107270A CN 1021009 C CN1021009 C CN 1021009C
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CN1032782A (en
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维维恩·玛格丽特·安东尼
斯蒂芬·保罗·希尼
凯文·博蒂蒙特
约翰·马丁·克拉夫
帕特里克·杰尔夫·克劳利
克里斯托弗·理查德·艾尔斯·戈弗雷
保罗·约翰·迪弗雷恩
艾伦·约翰·巴克利
迈克尔·戈登·哈钦斯
伊安·弗格森
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Syngenta Ltd
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Imperial Chemical Industries Ltd
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Priority claimed from GB888814734A external-priority patent/GB8814734D0/en
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Abstract

Fungicidal compounds of the formula (I): (I) and stereoisomers thereof, wherein K is oxygen or sulphur; Z is optionally substituted aryl or optionally substituted heteroaryl; X is a specified linking group; and A, B and E, which may be the same or different, are H, hydroxy, halo, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, C1-4 alkylcarbonyl, C1-4alkoxycarbonyl, phenoxy, nitro or cyano; except that when Z is unsubstituted phenyl and X and K are oxygen, A, B and E are not all hydrogen.

Description

Fungicides
The present invention relates to the acrylic acid derivative as bactericide, its preparation method contains the bactericidal composition of this composition, and uses it for killing fungus, particularly prevents the method for plant fungus infection.
EP-A-0178826 has described acrylic acid sterilization derivative and has enumerated compound (E)-methyl 2-(2-(3-phenoxy group phenoxy group) phenyl)-the 3-methoxy acrylate.
The invention provides the compound and the stereoisomer thereof of a kind of molecular formula (I):
Figure 881072702_IMG21
Wherein K is that oxygen or sulphur: Z is the aryl that replaces or do not replace or replacement or the heteroaryl that do not replace: X is O, S(O) n, NR 4, CR 1R 2, CHR 5, CO, CR 1(OR 2), C=CR 1R 2, CHR 1CHR 2, CR 1=CR 2, CHR 1CR 2=CH, C ≡ C, OCHR 1, CHR 1O, OCHR 1O, S(O) nCHR 1, S(O) nCHR 1O, CHR 1S(O) n, CHR 1OSO 2, NR 4CHR 1, CHR 1NR 4, CO 2, O 2C, SO 2O, OSO 2, CO.CO, COCHR 1, COCHR 1O, CHR 1CO, CHOH.CHR 1, CHR 1.CHOH,
Figure 881072702_IMG22
CONR 4, OCONR 4, NR 4CO, CSNR 4, OCS.NR 4, SCO.NR 4, NR 4CO 2, NR 4CS, NR 4CSO, NR 4COS, NR 4CONR 4, S(O) nNR 4, NR 4S(O) n, CS 2, S 2C, CO.S, SCO, N=N, N=CR 1, CR 1=N, CHR 1CHR 2CH(OH), CHR 1OCO, CHR 1SCO, CHR 1NR 4CO, CHR 1NR 4COR 4, CHR 1CHR 2CO, O.N=CR 1, CHR 1O.N=CR 2, CO.OCR 1R 2, CHR 1CHR 2CHR 3, OCHR 1CHR 2, (CH 2) mO, CHR 1OCHR 2, CHR 1CHR 2O, OCHR 1CHR 2O, S(O) nCHR 1CHR 2, CHR 1S(O) nCHR 2, CHR 1CHR 2S(O) n, CR 1=NNR 4, NR 4N=CR 1, CHR 1CONR 2, CHR 1OCO.NR 2, CH=CHCH 2O, COCHR 1CHR 2O, or (R 5) 2P +CHR 2O -;
A, B and E can be identical or different, and they are hydrogen, hydroxyl, halogen, C 1-4Alkyl, C 1-4Alkoxyl, C 1-4Haloalkyl, C 1-4Halogenated alkoxy, C 1-4Alkyl carbonyl, C 1-4Alkoxy carbonyl, phenoxy group, nitro or cyano group; R 1, R 2And R 3Can be identical or different, they are hydrogen, C 1-4Alkyl or phenyl; R 4Be H, C 1-4Alkyl or COR 1; R 5It is the phenyl that replaces or do not replace; Q -It is halide anion; N is 0,1 or 2, and m is 3,4 or 5; Except when Z is unsubstituted phenyl and X and K when being oxygen, A, B and E can not be hydrogen entirely.
Especially when Z was the heteroaryl that replaces or do not replace, X was O, S, SO 2, NH, NCH 3, NCOCH 3, CH(C 6H 5), CH(OH), CH=CH, OCH 2, CH 2O, CH(CH 3) O, S(O) CH 2, S(O) 2CH 2, SO 2O, CO.CH 2O or CO 2CH 2, particularly X is O, CH 2O, OCH 2, SO 2O or CH(OH) these compounds are particular importances.
Compound of the present invention contains the two keys of at least one carbon one carbon, and form that sometimes can the geometric isomer mixture obtains.And these mixtures are separable into various isomer, and the mixture that the present invention comprises these isomer and is made up of their all proportions comprises mainly mixture of being made up of (Z) isomer and the mixture of mainly being made up of (E) isomeric compound.
Usually use term " E " and " Z " to discern by the various isomer that the two keys of acrylate-based asymmetric replacement produce.These terms have a detailed description (seeing J March, " Advanced Organic Chemistry ", the third edition, Wileg-Interscince, 109 pages of beginnings) in the literature by the Cahn-Ingold-Prelog architectural definition.
The alternative bactericidal action of common a kind of ratios of the isomers is more effective, and effectively isomer is to be-CO in the opposite both sides of acrylate-based ethylene linkage 2CH 3With-OCH 3Base, these (E) isomer are the present invention's examples preferably.
Substituting group Z is the aryl that replaces or do not replace or replacement or the heteroaryl that do not replace in the compound (I), and chemical valence allows each replacement or the aryl that does not replace or heteroaryl can 5 substituting groups of as many as.Term " aryl " refers in particular to phenyl and naphthyl, and term " heteroaryl " comprises and contain one or more O that S and N(S or N are better) heteroatomic five yuan and hexa-member heterocycle base, thick benzenoid form and hetero-aromatic ring type, and corresponding N-oxide in each case.The example of heteroaryl, Z can be pyridine radicals, pyrimidine radicals, pyrazinyl, pyridazinyl, 1,2,3-, 1,2,4-and 1,3, the 5-triazinyl, 1,2,4,5-tetrazine base, 1,2,3-and 1,2,4-triazolyl, thienyl, furyl, pyrrole radicals, thiazolyl ， oxadiazole base, quinolyl, isoquinolyl, quinoxalinyl, benzothienyl, benzoxazolyl and benzothiazolyl, and suitable corresponding N-oxide.Be present in replacement or the aryl that does not replace and the substituting group of heteroaryl moieties and comprise one or more following radicals: halogen, hydroxyl, sulfydryl, C 1-4Alkyl (particularly methyl and ethyl), C 2-4Alkenyl (particularly pi-allyl), C 2-4Alkynyl (particularly propinyl), C 1-4Alkoxyl (particularly methoxyl group), C 2-4Alkenyloxy (particularly allyloxy), C 2-4Alkynyloxy group (particularly third alkynyloxy group), halo (C 1-4) alkyl (particularly trifluoromethyl), halo (C 1-4) alkoxyl (particularly trifluoromethoxy), C 1-4Alkyl thio-base (particularly methyl thio group), hydroxyl (C 1-4) alkyl, C 1-4Alkoxyl (C 1-4) alkyl, C 3-6Cycloalkyl, C 3-6Cycloalkyl (C 1-4) alkyl, the aryl that replaces or do not replace (the particularly phenyl that replaces or do not replace), the heteroaryl that replaces or do not replace (particularly pyridine radicals or the pyrimidine radicals that replaces or do not replace), the aryloxy group that replaces or do not replace (the particularly phenoxy group that replaces or do not replace), the heteroaryloxy that replaces or do not replace (particularly pyridine oxygen base or the 2-pyrimidinyl oxy that replaces or do not replace), the aryl (C that replaces or do not replace 1-4) alkyl (benzyl, phenethyl and the phenyl n-propyl group that particularly replace or do not replace), moieties wherein or do not replace or replace: hydroxyl, replacement or substituted heteroaryl (C not with following base 1-4) alkyl (pyridine that particularly replaces or do not replace-or pyrimidine (C 1-4) alkyl), the aryl (C that replaces or do not replace 2-4) alkenyl (phenyl vinyl that particularly replaces or do not replace), replace or substituted heteroaryl (C not 2-4) alkenyl (the pyridine vinyl or the pyrimidine vinyl that particularly replace or do not replace), replace or substituted aryl (C not 1-4) alkoxyl (particularly substituted benzyloxy), the heteroaryl (C that replaces or do not replace 1-4) alkoxyl (pyridine or the pyrimidine (C that particularly replace or do not replace 1-4) alkoxyl), replace or substituted aryloxy (C not 1-4) alkyl (particularly phenoxymethyl), the heteroaryloxy (C that replaces or do not replace 1-4) alkyl (the pyridine oxygen or the pyrimidine oxygen (C that particularly replace or do not replace 1-4) alkyl), acyloxy comprises C 1-4Alkanoyloxy (particularly acetoxyl group) and benzoyloxy group, cyano group, sulfo-cyanato-, nitro ,-NR ' R " ,-NHCOR ' ,-NHCONR ' R " and ,-CONR ' R " ,-COOR ' ,-OSO 2R ' ,-SO 2R ' ,-COR ' ,-CR '=NR ' or-N=CR ' R ", wherein R ' and R " is respectively a hydrogen, C 1-4Alkyl, C 1-4Alkoxyl, C 1-4Alkyl thio-base, C 3-6Cycloalkyl, C 3-6Cycloalkyl (C 1-4) alkyl, phenyl or benzyl, this phenyl and benzyl can be used halogen, C 1-4Alkyl or C 1-4Alkoxyl replaces.
Be present in arbitrary aromatic ring or the substituting group in the hetero-aromatic ring in the above-mentioned substituting group and be present in R 5Substituting group in the phenyl ring comprises one or more following radicals: halogen, hydroxyl, sulfydryl, C 1-4Alkyl, C 2-4Alkenyl, C 2-4Alkynyl, C 1-4Alkoxyl, C 2-4Alkenyloxy, C 2-4Alkynyloxy group, halo (C 1-4) alkyl, halo (C 1-4) alkoxyl, C 1-4Alkyl thio-base, hydroxyl (C 1-4) alkyl.C 1-4Alkoxyl (C 1-4) alkyl, C 3-6Cycloalkyl, C 3-6Cycloalkyl (C 1-4) alkyl, alkanoyloxy, benzyloxy, cyano group, sulfo-cyanato-, nitro ,-NR ' R " ,-NHCOR ' ,-NHCONR ' R " ,-CONR ' R " and ,-COOR ' ,-OSO 2R ' ,-SO 2R ' ,-COR ' ,-CR '=NR " or-N=CR ' R ", wherein R ' and R " meaning as above.
When arbitrary substituent A, B and E are C 1-4Alkyl or C 1-4During alkoxyl, this moieties can be straight chain or side chain, promptly can be methyl, ethyl, just or isopropyl, or just, secondary, the XOR tert-butyl group.Other C among the application 1-4Alkyl and C 1-4The implication of alkoxyl is identical.C 2-4Alkenyl can be straight chain or side chain, can have (E) configuration or (Z) configuration in the time of suitable.The example of these groups is vinyl, pi-allyl ,-C(CH 3): CH 2(E)-and (Z)-cyclobutenyl.
It is better that substituent A and B are positioned at the 4-and the 5-position of phenyl ring, and substituting group E is with little group or monatomic better as hydrogen or halogen.Usually, one or two among E and A, the B all is hydrogen.
A kind of situation, the present invention includes and have general formula (I compound a):
Figure 881072702_IMG23
Wherein, X is O, S(O) n(wherein n be 0,1 or 2), NH, NCH 3, NCH 2CH 3, NCOCH 3, NCH(CH 3) 2, CH 2, CH(CH 3), C(CH 3) 2, CO, C=CH 2, C=C(CH 3) 2, CH 2CH 2, CH(CH 3) CH 2, CH 2CH(CH 3), (E)-CH=CH, (Z)-CH=CH, (E)-C(CH 3)=C(CH 3), C ≡ C, OCH 2, OCH(CH 3), (CH 2) pO(wherein P be 1 to 5 integer), CH(CH 3) O, SCH 2, SCH(CH 3), S(O) CH 2, S(O) CH(CH 3), S(O) 2CH 2, S(O) 2CH(CH 3), CH 2S, CH(CH 3) S, CH 2S(O), CH(CH 3) S(O), CH 2S(O) 2, CH(CH 3) S(O) 2, NHCH 2, N(CH 3) CH 2, N(COCH 3) CH 2, NHCH(CH 3), N(CH 3) CH(CH 3), N(COCH 3) CH(CH 3), CH 2NH, CH 2N(CH 3), CH 2N(COCH 3), CH(CH 3) NH, CH(CH 3) N(CH 3), CH(CH 3) N(COCH 3), CO 2, O 2C, SO 2O, OSO 2, CO.CO, COCH 2, COCH(CH 3), CH 2CO, CH(CH 3) CO, CH(OH) CH 2, CH(OH) CH(CH 3), CH 2CH(OH), CH(CH 3) CH(OH), CONH, CON(CH 3), CON(CH 2CH 2CH 3), CON(CHO), CON(COCH 3), NHCO, N(CH 3) CO, N(CH 2CH 3) CO, N(CHO) CO, N(COCH 3) CO, CSN(CH 3), CSNH, NHCS, N(CH 3) CS, SO 2NH, SO 2N(CH 3), NHSO 2, N(CH 3) SO 2, N(CH 2CH 3) SO 2, CS 2, S 2C, COS, SCO, (E)-N=N, (E)-N=CH, (E)-N=C(CH 3), (E)-CH 2=N, (E)-C(CH 3)=N, CH 2CH 2CH 2, CH(CH 3) CH 2CH 2, CH 2CH(CH 3) CH 2, CH 2CH 2CH(CH 3), OCH 2CH 2, CH 2OCH 2, SCH 2CH 2, S(O) CH 2CH 2, S(O) 2CH 2CH 2, CH 2SCH 2, CH 2S(O) CH 2, CH 2S(O) 2CH 2, CH 2CH 2S, CH 2CH 2S(O), CH 2CH 2S(O) 2, (E)-CH=NNH, (E)-C(CH 3)=NNH, (E)-CH=NN(CH 3), (E)-NHN=CH, (E)-NHN=C(CH 3), (E)-N(CH 3) N=CH, CH 2CONH, CH(CH 3) CON(CH 3), CH(CH 3) CON(CH 3),
（E）-CH＝CHCH 2O，COCH 2CH 2O，
Figure 881072702_IMG24
CH(C 6H 5), COCH 2O, CH(OH), CO 2CH 2, (C 6H 5) 2P +CH 2Br -, CH 2OCO, CH 2NHCO, CH 2SCO, OCH 2O, OCH 2CH 2O, S(O) CH 2O, COCH(CH 3) O, (E)-CH 2ON=CH, (Z)-CH 2ON=CH, CH 2CH 2CH(OH), (E)-CH 2CH=CH, C(CH 3) (OH), CH 2OSO 2, CH 2NHCO.NH, OCO.NH, NHCO.NH or CH 2OCO.NH; A is H, hydroxyl, halogen, C 1-4Alkyl, C 1-4Alkoxyl, trifluoromethyl, nitro, cyano group, acetyl group or phenoxy group; B and E are H or halogen; D is H, hydroxyl, halogen, C 1-4Alkyl, C 1-4Alkoxyl, nitro, cyano group, halo (C 1-4) alkyl (particularly trifluoromethyl), halo (C 1-4) alkoxyl (particularly trifluoromethoxy), phenyl, phenoxy group, NHCOR 6, NHSO 2R 6, NR 7R 8, CO 2R 7, R wherein 6Be C 1-4Alkyl (particularly methyl) or phenyl, R 7And R 8Be respectively H or C 1-4Alkyl, or CH 3O 2C.C=CH.OCH 3; G is H, halogen, C 1-4Alkyl, C 1-4Alkoxyl or nitro; Perhaps D and G form phenyl ring or pyridine ring when adjacent; If A, B, D, E and G are H, and then X can not be O.More particularly, the present invention includes general formula (I compound a), wherein X is O, S(O) n(wherein n be 0,1 or 2), CH 2, CH 2CH 2, OCH 2, (CH 2) pO(wherein p be 1 to 5 integer), OCH 2O, OCH 2CH 2O, CH(OH), CO, CO 2, O 2C, COS, SCO, CO 2CH 2, SO 2O, (E)-CH=CH, (Z)-CH=CH, (E)-CH=CHCH 2O, CH(CH 3) O, SCH 2, SCH 2O, S(O) CH 2, S(O) CH 2O, S(O 2) CH 2, CONH, NH, NCH 3, CH 2NH, N(CH 3) CH 2, NHCO, CH 2OCO.NH, NCOCH 3, NHSO 2, (E)-N=N, (Z)-N=N, (E)-N=CH, (E)-N(CH 3) N=CH, (E)-CH 2ON=N, (Z)-CH 2ON=CH, CH(C 6H 5), COCH 2O, COCH(CH 3) O, CH 2OCO, CH 2NHCO, CH 2SCO or (C 6H 5) 2P +CH 2Br -; A is H, hydroxyl, halogen, C 1-4Alkyl, C 1-4Alkoxyl, acetyl group or phenoxy group; B and E are H; D is H, hydroxyl, halogen, C 1-4Alkyl, C 1-4Alkoxyl, nitro, cyano group, trifluoromethyl, trifluoromethoxy, phenyl, phenoxy group, amino or CH 3O 2C.C=CH.OCH 3; G is H, halogen, C 1-4Alkyl, nitro, perhaps D and G form phenyl ring or pyridine ring when adjacent; If A, B, D, E and G are H, then X can not be O.
Another kind of situation the present invention includes the compound of general formula (I b):
Figure 881072702_IMG25
Wherein, D and G are respectively halogens, C 1-4Alkyl, C 1-4Alkoxyl, trifluoromethyl, nitro, cyano group, phenyl, phenoxy group, NHCOR 6, NHSO 2R 6And NR 7R 8, R wherein 6And R 8Meaning above provide; A is a halogen, C 1-4Alkyl, C 1-4Alkoxyl, trifluoromethyl, nitro, cyano group, acetyl group or phenoxy group.
The compound that general formula (I b) is good especially is: wherein D is a hydrogen, and G is 2-or 3-chlorine, the 3-bromine, and 2-or 4-methoxyl group, 3-or 4-nitro, 2-or 3-cyano group or 3-or 4-phenoxy group, A is a hydrogen, and perhaps D and G are hydrogen, and A is 4-or 6-bromine or 4-or 6-acetyl group.
Also have a kind of situation, the present invention includes the compound of general formula (I c):
Figure 881072702_IMG26
Wherein Z is a pyridine radicals, pyrimidine radicals, triazinyl, pyrazinyl, pyridazinyl, quinolyl, benzoxazolyl, benzothiazolyl, thienyl, quinoxalinyl, thiazolyl, isoquinolyl, quinazolyl, purine radicals ， oxazolyl, thiadiazolyl group ， oxadiazole base, furyl, pyrrole radicals or Thienopyrimidine base, each can not replace or replace with following radicals: halogen, C 1-4Alkyl, C 1-4Alkoxyl, C 1-4Alkyl thio-base, halo (C 1-4) alkyl (particularly trifluoromethyl), cyano group, nitro, COOR 7, phenyl, phenoxy group, C 1-4Alkoxyl and CONR 7R 8, R wherein 7And R 8Be respectively H or C 1-4Alkyl; With their N-oxide; X is O, S, NH, N(CH 3), SO 2O, CH 2, CH 2CH 2, OCH 2, CH 2O, CH(OH), CONH or CO; A and B are respectively hydrogen, halogen, C 1-4Alkyl, C 1-4Alkoxyl, cyano group, nitro, halo (C 1-4) alkyl (particularly trifluoromethyl) or halo (C 1-4) alkoxyl (particularly trifluoromethoxy); E is H or halogen.
More particularly, the present invention includes the compound of general formula (I c), wherein X is O, S, OCH 2, SO 2O, CH 2, CH 2O, CONH or CON(CH 3); Z is pyridine-2-base, pyrimidine-2-base, pyrimidine-4-base, pyrimidine-5-base, pyrazine-2-base, pyridazine-3-base, 1,3,5-triazine-2-base, thiophene-2-base, pyrroles-2-base, quinoline-2-base, quinoxaline-2-base, 1,2, the 4-triazol-1-yl, thiazole-4-base, benzothiazole-2-base or benzo azoles-2-base, each can use hydrogen, trifluoromethyl, C 1-4Alkyl, C 1-4Alkoxyl, cyano group or nitro and their N-oxide replace or do not replace; A, B and E are H.
Also have a kind of situation, the present invention includes the compound of general formula (I d):
Figure 881072702_IMG27
X wherein, A, B, D, (I provides in a) implication of E and G, and X is O and A, and B, D and E are that the situation of H also is fine at compound.
The compound of good especially general formula (I d) is: wherein X is O, CH 2O or SO 2O, A, B, D, E and G are H, perhaps D is 2-or 4-nitro.
Also have a kind of situation, the present invention includes the compound of general formula (I e):
Z wherein, X, A, the implication of B and E provides in compound (I c).The compound of good especially general formula (I e) is: wherein Z is pyrimidine-2-base or pyrimidine-5-base, and X is O, and A, B and E are H.
Below with showing I, II, the compound of enumerating in III and IV explanation the present invention.In the table I, II, methyl 3-methoxy acrylate bases all in III and the IV have (E)-configuration.
The table I
Figure 881072702_IMG29
Compound
X D G A B E olefinic +Fusing point (℃)
Numbering
1 S H H H H H, 7.42 glue
2 SO H H H H H blur glue
3 SO 2H H H H H blurs wax
4 NH H H H H H, 7.44 waxes
5 NCH 3H H H H H 7.44 glue
6 NCH 2CH 3H H H H H
7 NCOCH 3H H H H H 7.39 50-54
8 NCH（CH 3） 2H H H H H
9 CH 2H H H H H 7.47 glue
10 CH（CH 3） H H H H H
11 C（CH 3） 2H H H H H
12 CO H H H H H, 7.47 glue
13 C：CH 2H H H H H
14 C：C（CH 3） 2H H H H H
15 CH 2CH 2H H H H H 7.49 glue
16 CH（CH 3）CH 2H H H H H
17 CH 2CH（CH 3） H H H H H
18 (E)-CH:CH H H H H H, 7.49 glue
The table I (continuous/D)
Compound
X D G A B E olefinic +Fusing point (℃)
Numbering
19 （E）-C（CH 3）：C（CH 3） H H H H H
20 C：C H H H H H
21 OCH 2H H H H H 7.46 glue
22 OCH（CH 3） H H H H H
23 CH 2O H H H H H 7.44 84
24 CH（CH 3）O H H H H H 7.39 99-102
25 SCH 2H H H H H 7.47 glue
26 SCH（CH 3） H H H H H
27 S（O）CH 2H H H H H 7.48 82-86
28 S（O）CH（CH 3） H H H H H
29 S（O） 2CH 2H H H H H 7.48 140-144
30 S（O） 2CH（CH 3） H H H H H
31 CH 2S H H H H H
32 CH（CH 3）S H H H H H
33 CH 2S（O） H H H H H
34 CH（CH 3）S（O） H H H H H
35 CH 2S（O） 2H H H H H
36 CH（CH 3）S（O） 2H H H H H
37 NHCH 2H H H H H
38 N(CH 3) CH 2H H H H H 7.44 glue
39 N（COCH 3）CH 2H H H H H
40 NHCH（CH 3） H H H H H
41 N（CH 3）CH（CH 3） H H H H H
42 N（COCH 3）CH（CH 3） H H H H H
43 CH 2NH H H H H H
44 CH 2N（CH 3） H H H H H
45 CH 2N（COCH 3） H H H H H
46 CH（CH 3）NH H H H H H
47 CH（CH 3）N（CH 3） H H H H H
The table I (continuous/D)
Compound
X D G A B E olefinic +Fusing point (℃)
Numbering
48 CH（CH 3）N（COCH 3） H H H H H
49 CO 2H H H H H 7.46 94-95
50 O 2C H H H H H 7.47 oil
51 SO 2O H H H H H 7.40 glue
52 OSO 2H H H H H
53 CO.CO H H H H H
54 COCH 2H H H H H
55 COCH（CH 3） H H H H H
56 CH 2CO H H H H H
57 CH（CH 3）CO H H H H H
58 CH（OH）CH 2H H H H H
59 CH（OH）CH（CH 3） H H H H H
60 CH 2CH（OH） H H H H H
61 CH（CH 3）CH（OH） H H H H H
62 CONH H H H H H, 7.46 glue
63 CON（CH 3） H H H H H
64 CON（CH 2CH 2CH 3） H H H H H
65 CON（CHO） H H H H H
66 CON（COCH 3） H H H H H
67 NHCO H H H H H, 7.40 glue
68 N（CH 3）CO H H H H H
69 N（CH 2CH 3）CO H H H H H
70 N（CHO）CO H H H H H
71 N（COCH 3）CO H H H H H
72 CSN（CH 3） H H H H H
73 CSNH H H H H H
The table I (continuous/D)
Compound
X D G A B E olefinic +Fusing point (℃)
Numbering
74 NHCS H H H H H
75 N（CH 3）CS H H H H H
76 SO 2NH H H H H H
77 SO 2N（CH 3） H H H H H
78 NHSO 2H H H H H 7.43 oil
79 N（CH 3）SO 2H H H H H
80 N（CH 2CH 3）SO 2H H H H H
81 CS 2H H H H H
82 S 2C H H H H H
83 COS H H H H H 7.38 87-91
84 SCO H H H H H, 7.50 glue
85 （E）-N：N H H H H H
86 (E)-N:CH H H H H H 7.49 or glue
7.50
87 （E）-N：C（CH 3） H H H H H
88 （E）-CH：N H H H H H
89 （E）-C（CH 3）：N H H H H H
90 CH 2CH 2CH 2H H H H H
91 CH（CH 3）CH 2CH 2H H H H H
92 CH 2CH（CH 3）CH 2H H H H H
93 CH 2CH 2CH（CH 3） H H H H H
94 OCH 2CH 2H H H H H
95 CH 2OCH 2H H H H H
96 CH 2CH 2O H H H H H 7.48 oil
97 SCH 2CH 2H H H H H
98 S（O）CH 2CH 2H H H H H
99 S（O） 2CH 2CH 2H H H H H
The table I (continuous/D)
Compound
X D G A B E olefinic +Fusing point
Numbering (℃)
100 CH 2SCH 2H H H H H
101 CH 2S（O）CH 2H H H H H
102 CH 2S（O） 2CH 2H H H H H
103 CH 2CH 2S H H H H H
104 CH 2CH 2S（O） H H H H H
105 CH 2CH 2S（O） 2H H H H H
106 （E）-CH：NNH H H H H H
107 （E）-C（CH 3）：NNH H H H H H
108 （E）-CH：NN（CH 3） H H H H H
109 （E）-NHN：CH H H H H H
110 （E）-NHN：C（CH 3） H H H H H
111 （E）-N（CH 3）N：CH H H H H H 7.50 121.5-
123.5
112 CH 2CONH H H H H H
113 CH（CH 3）CON（CH 3） H H H H H
114 CH（CH 3）CON（CH 3） H H H H H
115 (E)-CH:CHCH 2O H H H H H 7.47 glue
116 COCH 2CH 2O H H H H H
117 is trans H H H H H
118 is trans
Figure 881072702_IMG31
H H H H H
119 O 2-Cl H H H H 7.48 51-54
120 O 3-Cl H H H H, 7.48 glue
121 O 4-Cl H H H H
122 O 2-F H H H H, 7.50 glue
The table I (continuous/D)
Compound
X D G A B E olefinic +Fusing point (℃)
Numbering
123 O 3-F H H H H, 7.51 glue
124 O 4-F H H H H, 7.35 glue
125 O 2-CH 3H H H H 7.51 glue
126 O 3-CH 3H H H H 7.49 glue
127 O 4-CH 3H H H H 7.49 glue
128 O 2-CH 3O H H H H 7.46 glue
129 O 3-CH 3O H H H H 7.48 glue
130 O 4-CH 3O H H H H 7.48 glue
131 O 2-NO 2H H H H 7.47 glue
132 O 3-NO 2H H H H 7.49 glue
133 O 4-NO 2H H H H 7.44 67-71
134 O 2-CN H H H H 7.51 108-110
135 O 3-CN H H H H, 7.51 glue
136 O 4-CN H H H H
137 O 2-Br H H H H
138 O 3-Br H H H H, 7.48 glue
139 O 4-Br H H H H
140 O 2-CF 3H H H H
141 O 3-CF 3H H H H 7.49 oil
142 O 4-CF 3H H H H
143 O 2-C 6H 5O H H H H 7.46 glue
144 O 3-C 6H 5O H H H H 7.48 glue
145 O 4-C 6H 5O H H H H 7.50 glue
146 O 2-CH 3CH 2O H H H H
147 O 3-CH 3CH 2O H H H H
148 O 4-CH 3CH 2H H H H
The table I (continuous/D)
Compound
X D G A B E olefinic +Fusing point (℃)
Numbering
149 O 2-C 6H 5H H H H
150 O 3-C 6H 5H H H H 7.50 glue
151 O 4-C 6H 5H H H H
152 O 2-Cl 3-Cl H H H
153 O 2-Cl 4-Cl H H H
154 O 2-Cl 5-Cl H H H
155 O 2-Cl 6-Cl H H H
156 O 3-Cl 4-Cl H H H
157 O 3-Cl 5-Cl H H H, 7.53 glue
158 O 2-Cl 3-CH 3O H H H
159 O 2-Cl 4-CH 3O H H H
160 O 2-Cl 5-CH 3O H H H
161 O 2-Cl 6-CH 3O H H H
162 O 3-Cl 4-CH 3O H H H
163 O 3-Cl 5-CH 3O H H H
164 O 2-CH 3O 3-Cl H H H
165 O 2-CH 3O 4-Cl H H H
166 O 2-CH 3O 5-Cl H H H
167 O 3-CH 3O 4-Cl H H H
168 O
Figure 881072702_IMG32
Figure 881072702_IMG33
H H H
169 O
Figure 881072702_IMG34
H H H
170 O H H 2-F H H
171 O H H 4-F H H, 7.51 glue
172 O H H 5-F H H
173 O H H 6-F H H
174 O H H 4-Cl H H
The table I (continuous/D)
Compound
X D G A B E olefinic +Fusing point
Numbering (℃)
175 O H H 5-Cl H H, 7.41 glue
176 O H H 4-CH 3H H
177 O H H 5-CH 3H H 7.47 glue
178 O H H 4-CH 3O H H
179 O H H 5-CH 3O H H 7.42 glue
180 *O H H 4-Br H H 7.47 glue
181 O H H 5-Br H H
182 O H H 4-CF 3H H
183 O H H 5-CF 3H H
184 O H H 4-NO 2H H
185 O H H 5-NO 2H H
186 O H H 4-CN H H
187 O H H 5-CN H H
188 O H H 4-F 5-F H
189 O H H 4-Cl 5-Cl H
190 O H H 4-F 5-Cl H
191 O H H 4-Cl 5-F H
192 O H H 4-CH 3O 5-Cl H
193 O H H 4-CH 3O 5-F H
194 O H H H H 5-F
195 O H H H H 6-Cl
196 （E）-N：N H H 4-CH 3O H H
197 （E）-N：N H H 4-CH 3CH 2O H H
198 CH 2O 2-Cl H H H H
199 CH 2O 3-Cl H H H H
200 CH 2O 4-Cl H H H H
The table I (continuous/D)
Compound
X D G A B E olefinic +Fusing point
Numbering (℃)
201 CH 2O 2-F H H H H
202 CH 2O 3-F H H H H
203 CH 2O 4-F H H H H
204 CH 2O 2-CH 3H H H H 7.25 108-110
205 CH 2O 3-CH 3H H H H 7.24 glue
206 CH 2O 4-CH 3H H H H 7.40 88-90
207 CH 2O 2-CH 3O H H H H
208 CH 2O 3-CH 3O H H H H 7.39 glue
209 CH 2O 4-CH 3O H H H H
210 CH 2O 2-NO 2H H H H
211 CH 2O 3-NO 2H H H H
212 CH 2O 4-NO 2H H H H 7.42 109
213 CH 2O 2-CN H H H H
214 CH 2O 3-CN H H H H 7.41 89-92.5
215 CH 2O 4-CN H H H H
216 CH 2O 2-Br H H H H 7.41 78-80
217 CH 2O 3-Br H H H H 7.45 glue
218 CH 2O 4-Br H H H H 7.4 86-88.5
219 CH 2O 2-CF 3H H H H
220 CH 2O 3-CF 3H H H H blurs glue
221 CH 2O 4-CF 3H H H H
222 CH 2O 2-C 6H 5O H H H H
223 CH 2O 3-C 6H 5O H H H H
224 CH 2O 4-C 6H 5O H H H H
225 CH 2O 2-CH 3CH 2O H H H H
The table I (continuous/D)
Compound
X D G A B E olefinic +Fusing point
Numbering (℃)
226 CH 2O 3-CH 3CH 2O H H H H
227 CH 2O 4-CH 3CH 2O H H H H
228 CH 2O 2-C 6H 5H H H H
229 CH 2O 3-C 6H 5H H H H
230 CH 2O 4-C 6H 5H H H H blurs glue
231 CH 2O 2-Cl 3-Cl H H H
232 CH 2O 2-Cl 4-Cl H H H
233 CH 2O 2-Cl 5-Cl H H H
234 CH 2O 2-Cl 6-Cl H H H
235 CH 2O 3-Cl 4-Cl H H H
236 CH 2O 3-Cl 5-Cl H H H
237 CH 2O 2-Cl 3-CH 3O H H H
238 CH 2O 2-Cl 4-CH 3O H H H
239 CH 2O 2-Cl 5-CH 3O H H H
240 CH 2O 2-Cl 6-CH 3O H H H
241 CH 2O 3-Cl 4-CH 3O H H H
242 CH 2O 3-Cl 5-CH 3O H H H
243 CH 2O 2-CH 3O 3-Cl H H H
244 CH 2O 2-CH 3O 4-Cl H H H
245 CH 2O 2-CH 3O 5-Cl H H H
246 CH 2O 3-CH 3O 4-Cl H H H
247 CH 2O
Figure 881072702_IMG36
Figure 881072702_IMG37
H H H 7.42 100-102.5
248 CH 2O
Figure 881072702_IMG38
Figure 881072702_IMG39
H H H 7.42 102-106
249 CH 2O H H 2-F H H
250 CH 2O H H 4-F H H
The table I (continuous/D)
Compound
X D G A B E olefinic +Fusing point
Numbering (℃)
251 CH 2O H H 5-F H H
252 CH 2O H H 6-F H H
253 CH 2O H H 4-Cl H H
254 CH 2O H H 5-Cl H H
255 CH 2O H H 4-CH 3H H
256 CH 2O H H 5-CH 3H H
257 CH 2O H H 4-CH 3O H H
258 CH 2O H H 5-CH 3O H H
259 CH 2O H H 4-Br H H
260 CH 2O H H 5-Br H H
261 CH 2O H H 4-CF 3H H
262 CH 2O H H 5-CF 3H H
263 CH 2O H H 4-NO 2H H
264 CH 2O H H 5-NO 2H H
265 CH 2O H H 4-CN H H
266 CH 2O H H 5-CN H H
267 CH 2O H H 4-F 5-F H
268 CH 2O H H 4-Cl 5-Cl H
269 CH 2O H H 4-F 5-Cl H
270 CH 2O H H 4-Cl 5-F H
271 CH 2O H H 4-CH 3O 5-Cl H
272 CH 2O H H 4-CH 3O 5-F H
273 CH 2O H H H H 5-F
274 CH 2O H H H H 6-Cl
275 O 4-NH.COCH 3H H H H
The table I (continuous/D)
Compound
X D G A B E olefinic +Fusing point
Numbering (℃)
276 O 4-NH.SO 2C 6H 5H H H H
277 O 4-NH.COC 6H 5H H H H
278 O 4-NH.SO 2CH 3H H H H
279 O 4-N（CH 3） 2H H H H
280 SO 2O 4-NH.COCH 3H H H H
281 SO 2O 3-NO 24-Cl H H H
282 （E）-N：N 4-Cl H 4-HO H H 7.38 143-144
283 SO 2O 2-Cl H H H H 7.37 glue
284 SO 2O 3-Cl H H H H 7.45 glue
285 SO 2O 4-Cl H H H H 7.45 53-59
286 SO 2O 2-F H H H H
287 SO 2O 3-F H H H H
288 SO 2O 4-F H H H H 7.45 glue
289 SO 2O 2-CH 3H H H H
290 SO 2O 3-CH 3H H H H 7.34 glue
291 SO 2O 4-CH 3H H H H 7.38 70-76
292 SO 2O 2-CH 3O H H H H
293 SO 2O 3-CH 3O H H H H
294 SO 2O 4-CH 3O H H H H 7.39 96-97
295 SO 2O 2-NO 2H H H H 7.40 glue
296 SO 2O 3-NO 2H H H H 7.41 90-93.5
297 SO 2O 4-NO 2H H H H
298 SO 2O 2-CN H H H H
299 SO 2O 3-CN H H H H
300 SO 2O 4-CN H H H H
301 SO 2O 2-Br H H H H
The table I (continuous/D)
Compound
X D G A B E olefinic +Fusing point
Numbering (℃)
302 SO 2O 3-Br H H H H
303 SO 2O 4-Br H H H H
304 SO 2O 2-CF 3H H H H
305 SO 2O 3-CF 3H H H H
306 SO 2O 4-CF 3H H H H
307 SO 2O 2-C 6H 5O H H H H
308 SO 2O 3-C 6H 5O H H H H
309 SO 2O 4-C 6H 5O H H H H
310 SO 2O 2-CH 3CH 2O H H H H
311 SO 2O 3-CH 3CH 2O H H H H
312 SO 2O 4-CH 3CH 2O H H H H
313 SO 2O 2-C 6H 5H H H H
314 SO 2O 3-C 6H 5H H H H
315 SO 2O 4-C 6H 5H H H H
316 SO 2O 2-Cl 3-Cl H H H
317 SO 2O 2-Cl 4-Cl H H H
318 SO 2O 2-Cl 5-Cl H H H 7.53 glue
319 SO 2O 2-Cl 6-Cl H H H
320 SO 2O 3-Cl 4-Cl H H H
321 SO 2O 3-Cl 5-Cl H H H
322 SO 2O 2-Cl 3-CH 3O H H H
323 SO 2O 2-Cl 4-CH 3O H H H
324 SO 2O 2-Cl 5-CH 3O H H H
325 SO 2O 2-Cl 6-CH 3O H H H
326 SO 2O 3-Cl 4-CH 3O H H H
327 SO 2O 3-Cl 5-CH 3O H H H
328 SO 2O 2-CH 3O 3-Cl H H H
The table I (continuous/D)
Compound
X D G A B E olefinic +Fusing point
Numbering (℃)
329 SO 2O 2-CH 3O 4-Cl H H H
330 SO 2O 2-CH 3O 5-Cl H H H
331 SO 2O 3-CH 3O 4-Cl H H H
332 SO 2O
Figure 881072702_IMG40
H H H 7.34 glue
333 SO 2O
Figure 881072702_IMG42
H H H 7.35 98-100
334 SO 2O H H 2-F H H
335 SO 2O H H 4-F H H
336 SO 2O H H 5-F H H
337 SO 2O H H 6-F H H
338 SO 2O H H 4-Cl H H
339 SO 2O H H 5-Cl H H
340 SO 2O H H 4-CH 3H H
341 SO 2O H H 5-CH 3H H
342 SO 2O H H 4-CH 3H H
343 SO 2O H H 5-CH 3H H
344 SO 2O H H 4-Br H H
345 SO 2O H H 5-Br H H
346 SO 2O H H 4-CF 3H H
347 SO 2O H H 5-CF 3H H
348 SO 2O H H 4-NO 2H H
349 SO 2O H H 5-NO 2H H
350 SO 2O H H 4-CN H H
351 SO 2O H H 5-CN H H
352 SO 2O H H 4-F 5-F H
353 SO 2O H H 4-Cl 5-Cl H
354 SO 2O H H 4-F 5-Cl H
The table I (continuous/D)
Compound
X D G A B E olefinic +Fusing point
Numbering (℃)
355 SO 2O H H 4-Cl 5-F H
356 SO 2O H H 4-CH 3O 5-Cl H
357 SO 2O H H 3-CH 3O 5-F H
358 SO 2O H H H H 5-F
359 SO 2O H H H H 6-Cl
360 CH(C 6H 5) H H H H H 7.44 glue
361 O 3-Cl H 4-Cl H H
362 O 3-CH 3O 4-Cl 5-F H H
363 CH 2O 4-F H 5-CH 3O H H
364 SO 2O 3-CH 3H 4-F H H
365 O H H 4-CH 3CO H H 7.43 90-92
366
Figure 881072702_IMG45
O H H 6-CH 3CO H H 7.48 82-85
367 *O H H 6-Br H H 7.45 glue
368 O H H 5-C 6H 5O H H 7.46 glue
369 SO 2O 3-NH 2H H H H 7.43 88-92
370 COCH 2O H H H H H 7.47 49-52
371 OCH 24-CH 3O H H H H 7.49 66-69
372 OCH 23-CH 3O H H H H 7.47 glue
373 OCH 23-CN H H H H 7.48 71-75
374 OCH 24-CN H H H H 7.48 glue
375 OCH 24-NO 2H H H H 7.48 108-110
376 OCH 22-Cl H H H H 7.46 8
Figure 881072702_IMG46
-
Figure 881072702_IMG47
7
377 OCH 22-CH 3O H H H H 7.48 glue
378 OCH 22-CN H H H H 7.47 95-10
379 (E)-N:N 4-Cl H 4-CH 3O H H fuzzy 61
380 CH(OH) H H H H H 7.45 glue
The table I (continuous/D)
Compound
X D G A B E olefinic +Fusing point
Numbering (℃)
381 OCH 22-NO 2H H H H 7.48 glue
382 OCH 23-NO 2H H H H 7.48 glue
383 OCH 23-Br H H H H 7.47 oil
384 OCH 23-Cl H H H H 7.40 oil
385 OCH 23-C 6H 5O H H H H 7.47 oil
386 OCH 24-Cl H H H H 7.47 72-76
387 S（O）CH 24-Cl H H H H 7.42 105-11
388 S（O） 2CH 24-Cl H H H H 7.47 126-130.5
389 OCH 22-Br H H H H 7.46 87.5-9
390 O 2-NO 24-NO 2H H H 7.46 54-57
391 O 2-Me 3-Me H H H, 7.50 glue
392 O 2-Me 4-Me H H H, 7.51 glue
393 O 2-Me 5-Me H H H, 7.50 glue
394 O 2-Me 6-Me H H H, 7.50 glue
395 O 3-Me 4-Me H H H, 7.50 glue
396 O 3-Me 5-Me H H H, 7.51 waxes
397 OCH 24-Br H H H H 7.47 oil
398 CO 2CH 2H H H H H 7.47 glue
399 SCH 22-Cl H H H H 7.47 74-78
400 SCH 24-NO 2H H H H 7.48 glue
401 S(O) CH 22-Cl H H H H 7.60 glue
402 S(O) 2CH 22-Cl H H H H 7.59 glue
403 (E/Z)-CH=CH
Figure 881072702_IMG48
4-NO 2H H H H 7.49 glue
404 Ph 2 +PCH 2Br -H H H H H 7.40 176-177
405 CH 2O 4-tert-C 4H 9H H H H 7.31 glue
406 CH 2OCO H H H H H 7.46 glue
The table I (continuous/D)
Compound
X D G A B E olefinic +Fusing point
Numbering (℃)
407 CH 2NHCO H H H H H 7.41 glue
408 CH 2SCO H H H H H 7.45 glue
409 O 2C 3-NO 2H H H H 7.50 glue
410 OCH 2O 4-Cl H H H H 7.47 oil
411 S(O) CH 2O H H H H H 7.47 oil
412 COCH(CH 3) O H H H H H 7.45 oil
413 (E)-CH 2ON:CH H H H H H 7.49 glue
414 (Z)-CH 2ON:CH H H H H H 7.46 glue
415 (CH 2) 3O H H H H H 7.48 oil
416 (CH 2) 4O H H H H H 7.47 oil
417 (CH 2) 5O H H H H H 7.48 oil
418 (E)-N:N 4-OH H H H H, 7.50 oil
419 (E)-N:N 4-CH 3O H H H H 7.49 glue
420 CO.NH 2-Br H H H H, 7.49 foams
421 CO.NH 3-Br H H H H, 7.47 foams
422 CO.NH 3-CH 3O H H H H 7.48 foams
423 OCH 2CH 2O H H H H H 7.45 glue
424 SO 2O
Figure 881072702_IMG49
H H H 7.29 glue
425 SCH 2O H H H H H 7.47 oil
426 CH 2O 2-(CH 3O 2C-H H H H 7.40 or glue
C＝CH.OCH 3） 7.52
427 SO 2O 4-CF 3C H H H H blurs glue
428 SO 2O 2-CH 3O 2C H H H H 7.41 glue
429 CH 2CH 2CH（OH） H H H H H
430 （E）-CH 2CH＝CH H H H H H
The table I (continuous/D)
Compound
X D G A B E olefinic +Fusing point
Numbering (℃)
431 C（CH 3）（OH） H H H H H
432 CH（OH） 2-Cl H H H H
433 CH（OH） 4-Cl H H H H
434 CH（OH） 2-CH 3O H H H H
435 CH（OH） 3-CF 3H H H H
436 CH（OH） 3-CN H H H H
437 CH（OH） 4-NO 2H H H H
438 CH 2OSO 2H H H H H
439 CH 2NHCO.NH H H H H H
440 CH 2NH H H H H H
441 OCO.NH H H H H H
442 NHCO.NH H H H H H
443 CH 2OCO.NH H H H H H 7.47 glue
444 SO 2NH 4-Br H H H H
445 CH 2NH 3-CH 3H H H H
The table I is explained:
+: 'beta '-methoxy acrylic acid ester group (p.p.m, tetramethoxy-silicane) is gone up the single line displacement study of olefinic proton.
Solvent: CDCl 3(unless otherwise noted).
Figure 881072702_IMG51
: substituent group D and G link the formation condensed ring, like this, compound 168,169,247,248,332 and 333 are:
The X compound number
O 168
CH 2O 247
SO 2O 332
Figure 881072702_IMG53
The X compound number
O 169
CH 2O 248
SO 2O 333
Compound number 424 is:
Figure 881072702_IMG54
Figure 881072702_IMG55
Representing in all cases that structure is arranged can be opposite.In fact the characteristic of compound 180 can be a compound 367 also, and vice versa.Equally also can be applicable to compound 365 and 366.
≠ (E): (Z)=85: 15(sees example 20)
Ph is a phenyl.
The table II
Figure 881072702_IMG56
Compound
Z X A B E olefinic +Fusing point (℃)
Numbering
1 pyridine-2-base O H H H 7.48 glue
2 pyridines-2-base S H H H
3 pyridines-2-base N(CH 3) H H H
4 pyridines-2-base SO 2O H H H
5 pyridines-2-base CH 2CH 2H H H
6 pyridines-2-base OCH 2H H H 7.48 glue
7 pyridines-2-base CH 2O H H H
8 pyridin-3-yl O H H H, 7.48 glue
9 pyridin-3-yl S H H H
10 pyridin-3-yl N(CH 3) H H H
11 pyridin-3-yl SO 2O H H H
12 pyridin-3-yl CH 2CH 2H H H
13 pyridin-3-yl OCH 2H H H
14 pyridin-3-yl CH 2O H H H
The table II (continuous/D)
Compound
Z X A B E olefinic +Fusing point (℃)
Numbering
15 pyridin-4-yl O H H H, 7.48 glue
16 pyridin-4-yl S H H H
17 pyridin-4-yl N(CH 3) H H H
18 pyridin-4-yl SO 2O H H H
19 pyridin-4-yl CH 2CH 2H H H
20 pyridin-4-yl OCH 2H H H
21 pyridin-4-yl CH 2O H H H
22 pyrimidine-2-base O H H H, 7.38 glue
23 pyrimidine-2-base S H H H, 7.49 glue
24 pyrimidines-4-base N(CH 3) H H H
25 pyrimidines-4-base SO 2O H H H
26 pyrimidines-5-base CH 2CH 2H H H
27 pyrimidines-5-base CH 2O H H H
28 1,2,4-three OCH 2H H H
Piperazine-3-base
29 1,3,5-three O H H H
Piperazine-2-base
30 pyrazines-2-base O H H H 7.49 glue
31 pyrazines-2-base S H H H
32 pyrazines-2-base N(CH 3) H H H
33 pyrazines-2-base SO 2O H H H
The table II (continuous/D)
Compound
Z X A B E olefinic +Fusing point (℃)
Numbering
34 pyrazines-2-base CH 2O H H H
35 pyridazines-3-base O H H H 7.49 glue
36 pyridazines-3-base S H H H
37 pyridazines-3-base SO 2O H H H
38 quinoline-2-base O H H H 7.43 109-110
39 quinoline-2-base CH 2O H H H
40 quinoline-3-base O H H H
41 quinoline-3-base SO 2O H H H
42 benzoxazolyls-2-base O H H H
43 benzoxazolyls-2-base S H H H
44 benzoxazolyls-2-base N(CH 3) H H H
45 benzoxazolyls-2-base SO 2O H H H
46 benzothiazoles-2-base CH 2CH 2H H H
47 benzothiazoles-2-base OCH 2H H H 7.49 glue
48 benzothiazoles-2-base CH 2O H H H
49 thiophene-2-base CH 2O H H H
50 thiophene-2-base CH 2CH 2H H H
51 thiene-3-yl-O H H H
52 thiophene-2-base SO 2O H H H 7.40 glue
53 5-CF 3-pyrrole O H H H 7.49 oil
Pyridine-2-base
The table II (continuous/D)
Compound
Z X A B E olefinic +Fusing point (℃)
Numbering
54 5-CF 3-pyrrole S H H H
Pyridine-2-base
55 5-CF 3-pyrrole CH 2O H H H
Pyridine-2-base
56 3-F-pyridine O H H H
-2-base
57 3-F-pyridine O H H H
-2-base
58 4-Br-pyrrole O H H H
Pyridine-2-base
59 5-CH 3-pyrrole O H H H
Pyridine-2-base
60 6-CH 3O- O H H H
Pyridine-2-base
61 2-F-pyridine O H H H
-3-base
62 3-CF 3-pyrrole O H H H
Pyridine-4-base
63 4,6-two fluoro-O H H H
Pyridine-2-base
The table II (continuous/D)
Compound
Z X A B E olefinic +Fusing point (℃)
Numbering
64 3-NO 2-5- O H H H
CF 3-pyridine-2-base
65 5-（CH 3O 2C） O H H H
-pyridine-2-base
66 3-CH 3-pyridine O H H H
-2-base
67 4-CH 3-pyridine O H H H
-2-base
68 6-CH 3-pyridine O H H H
-2-base
69 5-(CN)-pyridine O H H H 7.49 glue
-2-base
70 3-Cl-5- O H H H
（C 6H 5O）-1，
3,5-triazine-2-base
71 pyridines-2-base O 2-F H H
72 pyridines-2-base O 4-Cl H H
73 pyridin-4-yl O 5-CH 3H H
74 pyridin-4-yl O 4-CH 3O H H
The table II (continuous/D)
Compound olefinic fusing point
Z X A B E
Numbering +(℃)
75 5-CF 3- O 5-CN H H
Pyridine-2-base
76 5-CF 3- O 4-F 5-CH 3O H
Pyridine-2-base
77 pyrimidine-2-base O H H 5-Cl
78 pyrimidine-2-base O H H 6-F
79 benzoxazole O 4-CF 3O H 5-F
Base-2-base
80 benzoxazole O 5-NO 2H H
Base-2-base
81 1,2,4-CH 2H H H 7.48 glue
Triazol-1-yl
82 1，2，3- CH 2H H H
Triazol-1-yl
83 benzothiazole O H H H, 7.38 glue
-2-base
84 3-chloro quinoline O H H H, 7.50 117-119
Quinoline base-2-base
85 pyrimidine-2-base OCH 2H H H 7.49 oil
86 3,5-dichloro O H H H 7.52 glue
-1，3，5-
Triazine-2-base
The table II (continuous/D)
Compound
Z X A B E olefinic +Fusing point (℃)
Numbering
87 pyrimidines-5-base O H H H 7.47 oil
88 3-Cl, 5-O H H H 7.50 glue
（CH 3O）-
1,3,5-triazines
89 6-Cl-pyrimidine O H H H, 7.49 oil
-4-base
90 5-Br-pyrimidine O H H H, 7.48 glue
-2-base
91 5-Cl-pyrimidine O H H H, 7.48 oil
-2-base
92 pyrimidines-4-base O H H H 7.48 oil
93 2,6-dimethoxy O H H H 7.48 oil
Base-pyrimidine-4-base
94 2-Cl-6- O H H H 7.50 113-118
CH 3-pyrimidine-4-base
95 2,6-two chloro-O H H H 7.50 113-115
Pyrimidine-4-base
96 2,5,6-trichlorine O H H H 7.49 glue
-pyrimidine-4-base
97 2-Cl-pyrimidine O H H H * oil
-4-base
The table II (continuous/D)
Compound
Z X A B E olefinic +Fusing point (℃)
Numbering
98 2-CH 3-thiazole CH 2O H H H 7.48 oil
-4-base
99 benzoxazoles-2 OCH 2H H H 7.50 glue
100 pyrazines-2-base OCH 2H H H 7.49 glue
101 6-Cl-pyrazine OCH 2H H H 7.49 glue
-2-base
102 quinoline-2-base OCH 2H H H 7.49 glue
103 6-Cl-pyridazine OCH 2H H H 7.49 glue
-3-base
104 pyridines-4, OCH 2H H H 7.49 foams
The N-oxide
105 5-CF 2-pyrrole OCH 2H H H 7.48 glue
Pyridine-2-base
106 3-cyanopyridine O H H H, 7.48 glue
-2-base
107 5-NO 2-pyrrole O H H H 7.49 glue
Pyridine-2-base
108 pyrimidine-2-base CH 2O H H H
109 pyrimidine-2-base SO 2O H H H
110 pyrimidine-2-base NH H H H
111 pyrimidine-2-base N(CH 3) H H H
The table II (continuous/D)
Compound
Z X A B E olefinic +Fusing point (℃)
Numbering
112 pyrimidine-2-base CH 2H H H
113 pyrimidine-2-base CH(OH) H H H
114 pyrimidine-2-base CH 2CH 2H H H
115 pyrimidines-4-base O H H H
116 pyrimidines-4-base CH 2O H H H
117 pyrimidines-4-base OCH 2H H H
118 pyrimidines-4-base NH H H H
119 pyrimidines-4-base S H H H
120 pyrimidines-4-base CH 2H H H
121 pyrimidines-4-base CH(OH) H H H
122 pyrimidines-4-base CH 2CH 2H H H
123 pyrimidines-5-base SO 2O H H H
124 pyrimidines-5-base OCH 2H H H
125 pyrimidines-5-base NH H H H
126 pyrimidines-5-base N(CH 3) H H H
127 pyrimidines-5-base S H H H
128 pyrimidines-5-base CH 2H H H
129 pyrimidines-5-base CH(OH) H H H
130 6-chlorine pyridazines-3-base O H H H 7.50 glue
131 6-chlorine pyridazines-3-base CH 2O H H H
132 6-chlorine pyridazines-3-base NH H H H
The table II (continuous/D)
Compound
Z X A B E olefinic +Fusing point (℃)
Numbering
133 6-chlorine pyridazines-3-base N(CH 3) H H H
134 6-chlorine pyridazines-3-base CH(OH) H H H
135 pyridazines-4-base O H H H
136 pyridazines-4-base OCH 2H H H
137 pyridazines-4-base NH H H H
138 pyridazines-4-base SO 2O H H H
139 1,3,5-triazines NH H H H
-2-base
140 1,3,5-triazines N(CH 3) H H H
-2-base
141 1,2,4-triazine O H H H
-2-base
142 1,2,4-triazine NH H H H
-3-base
143 1,2,4-triazine N(CH 3) H H H
-3-base
144 1,2,4-triazine O H H H
-5-base
145 1,2,4-triazine NH H H H
-5-base
The table II (continuous/D)
Compound
Z X A B E olefinic +Fusing point (℃)
Numbering
146 1,2,4-triazine O H H H
-6-base
147 1,2,4-triazine N(CH 3) H H H
-6-base
148 pyrimidines-2, O H H H
The N-oxide
149 pyrimidines-4,1-O H H H
The N-oxide
150 pyrimidines-4,3-O H H H
The N-oxide
151 pyridines-2, O H H H
The N-oxide
152 pyridines-3, O H H H
The N-oxide
153 pyrazines-2,1-O H H H
The N-oxide
154 pyrazines-2,4-O H H H
The N-oxide
155 pyridazines-3,1-O H H H
The N-oxide
The table II (continuous/D)
Compound
Z X A B E olefinic +Fusing point (℃)
Numbering
156 pyridazines-3,2-O H H H
The N-oxide
157 isoquinolyl-1 O H H H
158 isoquinolyl-1 NH H H H
159 isoquinolyl-1 CH 2O H H H
160 isoquinolyl-1 OCH 2H H H
161 isoquinolyl-1 CH(OH) H H H
162 isoquinolyl-1 S H H H
163 isoquinolyl-1 SO 2O H H H
164 quinolyl-4 O H H H
165 quinolyl-4 NH H H H
166 quinolyl-4 CH 2O H H H
167 quinolyl-4 OCH 2H H H
168 quinolyl-4 CH(OH) H H H
169 quinolyl-4 S H H H
170 quinolyl-4 SO 2O H H H
171 quinazolines-4-base O H H H
172 quinazolines-4-base NH H H H
173 quinazolines-4-base CH 2O H H H
174 quinazolines-4-base OCH 2H H H
175 quinazolines-4-base CH(OH) H H H
The table II (continuous/D)
Compound
Z X A B E olefinic +Fusing point (℃)
Numbering
176 quinazolines-4-base S H H H
177 quinazolines-4-base SO 2O H H H
178 7-chloro quinoline O H H H
-4-base
179 7-chloro quinoline S H H H
-4-base
180 7-chloro quinoline NH H H H
-4-base
181 purine-6-base O H H H
182 2-chloro-purine S H H H
-6-base
183 2-chloro-purine NH H H H
-6-base
184 5-NO 2-thiophene OCH 2H H H
Fen-2-base
185 5-NO 2-thiophene O H H H
Fen-2-base
186 thiazolyls-2-base CH 2O H H H
187 thiazolyls-2-base O H H H
188 thiazolyls-2-base NH H H H
189 thiazolyls-4-base CH 2O H H H
The table II (continuous/D)
Compound
Z X A B E olefinic +Fusing point (℃)
Numbering
190 thiazolyls-4 O H H H
191 thiazolyls-4 NH H H H
192 thiazolyls-5 CH 2O H H H
193 thiazolyls-5 O H H H
194 thiazolyls-5 NH H H H
195 oxazoles-2 CH 2O H H H
196 oxazoles-4 O H H H
197 oxazoles-5 NH H H H
198 5-CF 3-1，3，4 O H H H
-thiadiazoles-2
199 5-CF 3-1，3，4 OCH 2H H H
-thiadiazoles-2
200 4-Cl-1，2，5 O H H H
-thiadiazoles-3
201 O H H H 7.49 115-116
202
Figure 881072702_IMG58
NH H H H
203
Figure 881072702_IMG59
N（CH 3） H H H
The table II (continuous/D)
Compound
Z X A B E olefinic +Fusing point (℃)
Numbering
204 4-Cl-pyrimidine-2-base O H H H
205 4-Br-pyrimidine-2-base O H H H
206 4-F-pyrimidine-2-base O H H H
207 4-CH 3-pyrimidine-2-base O H H H
208 4-CH 3O-pyrimidine-2-base O H H H
209 4-CH 3CH 2The phonetic O H of O-H H
Pyridine-2-base
210 4-NO 2-pyrimidine-2-base O H H H
211 4-cyano group-pyrimidine-2-base O H H H
212 4-CF 3-pyrimidine-2-base O H H H
213 4-C 6H 5-pyrimidine-2-base O H H H
214 4-C 6H 5O-pyrimidine O H H H
-2-base
215 5-F-pyrimidine-2-base O H H H
216 5-CH 3-pyrimidine-2-base O H H H
217 5-CH 3O-pyrimidine-2-base O H H H
218 5-CH 3CH 2O-pyrimidine O H H H
-2-base
219 5-NO 2-pyrimidine-2-base O H H H
220 5-cyano group-pyrimidine-2-base O H H H
The table II (continuous/D)
Compound
Z X A B E olefinic +Fusing point (℃)
Numbering
221 5-CF 3-pyrimidine-2-base O H H H
222 5-C 6H 5-pyrimidine-2-base O H H H
223 5-C 6H 5O-pyrimidine O H H H
-2-base
224 4,5-dichloro pyrimidine-2-base O H H H
225 4,6-dichloro pyrimidine-2-base O H H H
226 4-Cl-6-CH 3-phonetic O H H H
Pyridine-2-base
227 4-Cl-5-CH 3O- O H H H
Pyrimidine-2-base O
228 2-F-pyrimidine-4-base O H H H
229 2-Br-pyrimidine-4-base O H H H
230 2-CH
Figure 881072702_IMG60
-pyrimidine-4-base O H H H
231 2-CH 3O-pyrimidine-4-base O H H H
232 2-CH 3CH 2O-pyrimidine O H H H
-4-base
233 2-NO 2-pyrimidine-4-base O H H H
234 2-CH 3S-pyrimidine-4-base O H H H
235 2-cyano group-pyrimidines-4-base O H H H
236 2-CF 3-pyrimidine-4-base O H H H
The table II (continuous/D)
Compound
Z X A B E olefinic +Fusing point (℃)
Numbering
237 2-C 6H 5O-pyrimidine O H H H
-4-base
238 2-C 6H 5-pyrimidine O H H H
-4-base
239 6-F-pyrimidine-4-base O H H H
240 6-Br-pyrimidine-4-base O H H H
241 6-CH 3-pyrimidine O H H H
-4-base
242 6-CH 3O-pyrimidine O H H H
-4-base
243 6-CH 3CH 2O- O H H H
Pyrimidine-4-base
244 6-NO 3-pyrimidine O H H H
-4-base
245 6-cyano group-pyrimidine O H H H
-4-base
246 6-CF 3-pyrimidine O H H H
-4-base
247 6-C 6H 5O- O H H H
Pyrimidine-4-base
The table II (continuous/D)
Compound
Z X A B E olefinic +Fusing point (℃)
Numbering
248 6-C 6H 5-pyrimidine-4-base O H H H
249 5-F-pyrimidine-4-base O H H H
250 5-Cl-pyrimidine-4-base O H H H
251 5-Br-pyrimidine-4-base O H H H
252 5-CH 3-pyrimidine-4-base O H H H
253 5-CH 3O-pyrimidine-4-base O H H H
254 5-CH 3CH 2O- O H H H
Pyrimidine-4-base
255 5-NO 2-pyrimidine-4-base O H H H
256 5-cyano group-pyrimidines-4-base O H H H
257 5-CF 3-pyrimidine-4-base O H H H
258 5-C 6H 5O-pyrimidine O H H H
-4-base
259 5-C 6H 5-pyrimidine-4-base O H H H
260 2-Cl-pyrimidine-5-base O H H H
261 2-CH 3-pyrimidine-5-base O H H H
262 2-F-pyrimidine-5-base O H H H
263 2-CH 3O-pyrimidine-5-base O H H H
264 2-cyano group-pyrimidines-5-base O H H H
265 4-CH 3-pyrimidine-5-base O H H H
266 4-CH 3O-pyrimidine-5-base O H H H
The table II (continuous/D)
Compound
Z X A B's +Fusing point (℃)
Numbering
267 4-CF 3-pyrimidine O H H H
-5-base
268 2,4-dimethyl O H H H
-pyrimidine-5-base
269 2-CH 3S-4- O H H H
CH 3O-pyrimidine-5-base
270 pyrrole radicals-2-base CONH H H H 7.48 foams
271 6-Cl-3-NO 2O H H H 7.50 glue
-pyridine-2 He
6-Cl-5-NO 2
-pyridine-2-base
1:1 mixes
272 3,6-dimethyl pyrazole O H H H 7.49 glue
Piperazine-2-base
273 6-Cl-pyrazine-2-base O H H H 7.50 glue
274 6-CH 3O-pyridazine O H H H 7.50 glue
-2-base
275 6-Cl-4-CH 3O H H H
-pyridazine-3-base
276 6-Cl-5-CH
Figure 881072702_IMG61
O H H H
-pyridazine-3-base
The table II (continuous/D)
Compound
Z X A B E olefinic +Fusing point (℃)
Numbering
277 4-CF 3-pyridine-2-base O H H H
278 6-cyanopyridine-2-base O H H H
279 4-cyanopyridine-2-base O H H H
280 4-acetylpyridine-2 O H H H
281 6-C 6H 5-pyridazine O H H H
-2-base
282 3-(CH 3O 2C)-pyrrole O H H H
Pyridine-2-base
283 5-(CH 3O 2C)-pyrrole O H H H
Pyridine-3-base
284 4-CF 2Cl-pyridine O H H H
-2-base
285 3,5-two-CF 3-O H H H
Pyridine-2-base
286 6-CF 3-pyridine-2-base O H H H
287 5-CF 3-pyridin-3-yl O H H H
288 2-Cl-pyridin-3-yl O H H H
289 2-CH 3O-pyridin-3-yl O H H H
290 2-Cl-pyridin-4-yl O H H H
291 2-CH 3O-pyridin-4-yl O H H H
292 2-Cl-pyridine-5-base O H H H
The table II (continuous/D)
Compound
Z X A B E olefinic +Fusing point (℃)
Numbering
293 2-CH 3O-pyridine O H H H
-5-base
294 3-CH 3S-pyridine O H H H
-2-base
295 4-CF 3O-pyridine O H H H
-2-base
296 4-CON（CH 3） 2O H H H
-pyridine-2-base
297 3-Cl-1，2，4 O H H H
-oxadiazoles-5-base
298 3-Cl-1，2，4 S H H H
-oxadiazoles-5-base
299 5-CH
Figure 881072702_IMG62
S-1，2，4 O H H H
-oxadiazoles-3-base
300 pyridines-2-base CH(OH) H H H
301 pyridin-3-yl CH(OH) H H H
302 pyridin-4-yl CH(OH) H H H
303 pyridines-2-base CO H H H
304 pyridin-3-yl CO H H H
305 pyridin-4-yl CO H H H
306 thiophene-2-base CH(OH) H H H
The table II (continuous/D)
Compound
Z X A B E olefinic +Fusing point (℃)
Numbering
307 furans-2-base CH(OH) H H H
308 N-CH 3-pyrroles CH(OH) H H H
-2-base
309 N-CH
Figure 881072702_IMG63
-pyrroles CO H H H
-2-base
310 6-Br-pyridine OCH 2H H H 7.49 oil
-2-base
311 4-Cl-pyrimidine OCH 2H H H 7.49 oil
-2-and 2-Cl
-pyrimidine-4-base
(3:1 mixes, no
Must separate)
312 2,6-fluoropyrimidine O H H H
-4-base
313 2-CH S-6-O H H H 7.48 glue
CH
Figure 881072702_IMG65
-pyrimidine-4
314 2-CH S-pyrimidine O H H H
-4-base
315 N-CH 3-pyrroles CON-CH 3H H H 7.47 glue
-2-base
The table II (continuous/D)
Compound
Z X A B E olefinic +Fusing point (℃)
Numbering
316 5-CF 3-pyridine NH H H H
-2-base
317 2-Cl-pyrimidine NH H H H
-4-base
318 4-Cl-pyrimidine NH H H H
-2-base
319 5-NO 2-6-O H H H 7.48 glue
(CH 3) 2The N-pyrrole
Pyridine-2-base
320 6-Cl-4-CH 3O H H H 7.50 glue
-pyridazine-3 and 6-
Cl-5-CH 3-rattle away
Piperazine-3-base
(the 3:2 mixture,
Needn't separate)
Annotate:
+: the single line displacement study of olefinic proton (p.p.m, tetramethylsilane) on the 'beta '-methoxy acrylic acid ester group.
Solvent: CDCl 3(unless otherwise noted).
*: carbon-13n.m.r. data see Table V.
The table III
Figure 881072702_IMG67
The table III contains the compound of 446 kinds of said structure formulas.The X of preceding 445 kinds of compounds, D, G, A, the implication of B and E is listed in the I at table, promptly shows No. 1 to 445, compound in the III, except K is an oxygen in the table I, is beyond the sulphur in the table III, and all the compound with the table I is identical for all the other.Compound has top structure No. 446, and wherein X is an oxygen, A, and B, D, E and G are hydrogen.The preparation method of No. 446 compounds is described in example 11.
The table III
The compound olefinic +Fusing point (℃)
X D G A B E
Numbering
23 CH 2O H H H H H 7.49 glue
51 SO 2O H H H H H 7.46 glue
131 O 2-NO 2H H H H 7.48 glue
212 CH 2O 4-NO 2H H H H 7.49 glue
446 O H H H H H 7.48 48-51.5
The table IV
Figure 881072702_IMG68
The table IV comprises the compound of 320 kinds of said structure formulas, all substituting group Z, and X, A, the implication of B and E all is listed in the table II, promptly shows 1 in the IV to No. 320 compounds, except K is an oxygen in the table II, is outside the sulphur in the table IV, and all the other are identical with the table II all.
Compound
Z X A B E olefinic +Fusing point (℃)
Numbering
22 Pyrimidin-2-yl O H H H, 7.49 glue
87 Pyrimidin-5-yl O H H H, 7.48 glue
Table V: the NMR value of selecting proton
The table V is represented the his-and-hers watches I, II, the n.m.r value of the selected proton of narrating in III and the IV of some compound.From tetramethylsilane, measure chemical shift, all use deuterochloroform to make solvent with p.p.m.Hurdle topic " frequency " is meant the n.m.r(nuclear magnetic resonnance) operating frequency of spectrometer.Use following abbreviation:
The br=bandwidth
The s=single line
The d=two-wire
The t=triplet
The q=quartet
The m=multiplet
Table sequence number compound number frequency
（MHz）
Ⅰ 2 60 3.36（3H，s），3.46（3H，s），
6.6-7.6（14H，m）ppm.
Ⅰ 7 60 1.98（3H，s），3.48（3H，s），
3.59（3H，s），6.6-7.3（13H，
m），7.39（1H，s）ppm.
Ⅰ 15 270 2.88（4H，s），3.60（3H，s），
3.77（3H，s），6.76-3.93
（4H，m），7.07-7.33（9H，m），
7.49（1H，s）ppm.
Ⅰ 25 270 3.59（3H，s），3.74（3H，s），
4.05（2H，s），6.80-7.32
（13H，m），7.47（1H，s）ppm.
Ⅰ 27 270 3.60（3H，s），3.77（3H，s），
3.98（2H，q），6.60-6.90
（4H，m），7.10-7.30（4H，m），
7.39-7.50（5H，m），7.48
（1H，s）ppm.
Ⅰ 29 400 3.59（3H，s），3.77（3H，s），
4.26（2H，s），6.70-6.90
（4H，m），7.10-7.30（5H，m），
7.45-7.52（1H，m），7.48
（1H，s），7.60-7.70（3H，m）
ppm.
Ⅰ 38 270 2.99（3H，s），3.56（3H，s），
3.69（3H，s），4.46（2H，s），
Table sequence number compound number frequency
（MHz）
6.65-6.73（3H，t），6.79
（1H，d），6.85-6.95（3H，t），
7.10（1H，t），7.16-7.29
（5H，m），7.44（1H，s）ppm.
Ⅰ 62 270 3.61（3H，s），3.78（3H，s），
6.7-7.6（11H，m），7.46（1H，
s），7.8（3H，m）ppm.
Ⅰ 67 270 3.59（3H，s），3.79（3H，s），
7.02-7.40（10H，m），7.40
（1H，s），7.70（2H，d），8.32
（1H，s）ppm.
Ⅰ 84 270 3.60（3H，s），3.75（3H，s），
6.97（1H，d），7.14-7.53
（11H，m），7.50（1H，s），
7.59（1H，d），7.70（1H，d）
ppm.
Ⅰ 86 400 3.60（3H，s），3.74（3H，s），
6.99（1H，d），7.09（1H，d），
7.12-7.41（9H，m），7.49
（1H，s），7.50（1H，s），7.59
（1H，d），8.38（1H，s）ppm.
Ⅰ 96 400 3.07（2H，t），3.60（3H，s），
3.75（3H，s），4.10（2H，t），
6.5-7.4（13H，m），7.48
（1H，s）ppm.
Table sequence number compound number frequency
（MHz）
Ⅰ 115 270 3.60（3H，s），3.75（3H，s），
4.63（2H，d），6.3-7.4（15H，
m），7.47（1H，s）ppm.
Ⅰ 119 270 3.60（3H，s），3.76（3H，s），
6.58-6.72（3H，m），6.96-
7.32（8H，m），7.41-7.50
（1H，m），7.48（1H，s）ppm.
Ⅰ 120 270 3.60（3H，s），3.76（3H，s），
6.62-7.36（12H，m），7.48
（1H，s）ppm.
Ⅰ 122 90 3.61（3H，s），3.77（3H，s），
6.5-6.8（3H，m），6.9-7.4
（9H，m），7.50（1H，s）ppm.
Ⅰ 123 90 3.64（3H，s），3.79（3H，s），
6.6-6.9（2H，m），6.9-7.5
（10H，m），7.51（1H，s）ppm.
Ⅰ 125 90 2.23（3H，s），3.61（3H，s），
3.77（3H，s），6.5-6.8（3H，m），
6.8（3H，m），6.8-7.5（9H，m），
7.51（1H，s）ppm.
Ⅰ 126 400 2.33（3H，s），3.61（3H，s），
3.76（3H，s），6.62-7.3
（12H，m），7.49（1H，s）ppm.
Table sequence number compound number frequency
（MHz）
Ⅰ 127 90 2.32（3H，s），3.60（3H，s），
3.75（3H，s），6.62-7.40
（12H，m），7.49（1H，s）ppm.
Ⅰ 128 270 3.58（3H，s），3.74（3H，s），
3.82（3H，s），6.56-6.65
（3H，m），6.84-7.00（4H，m），
7.06-7.28（5H，m），7.46
（1H，s）ppm.
Ⅰ 130 60 3.6（3H，s），3.75（3H，s），
3.8（3H，s），6.57-7.3（12H，
m），7.48（1H，s）ppm.
Ⅰ 131 270 3.61（3H，s），3.76（3H，s），
6.62-6.79（3H，m），6.97-
7.34（7H，m），7.47（1H，s），
7.48-7.56（1H，m），7.94
（1H，d）ppm.
Ⅰ 135 90 3.62（3H，s），3.78（3H，s），
6.6-6.9（3H，m），6.9-7.6
（9H，m），7.51（1H，s）ppm.
Ⅰ 138 270 3.60（3H，s），3.76（3H，s），
6.62-6.76（3H，m），6.90-
7.02（2H，m），7.12-7.38
（7H，m），7.48（1H，s）ppm.
Table sequence number compound number frequency
（MHz）
Ⅰ 141 250 3.59（3H，s），3.70（3H，s），
6.6-6.8（3H，m），6.9-7.1
（1H，m），7.1-7.5（8H，m），
7.49（1H，s）ppm.
Ⅰ 143 90 3.56（3H，s），3.68（3H，s），
6.54-7.36（17H，m），7.46
（1H，s）ppm.
Ⅰ 144 400 3.60（3H，s），3.75（3H，s），
6.65-6.76（5H，m），6.97（1H，
d），7.02（2H，d），7.10-7.38
（9H，m），7.48（1H，s）.
Ⅰ 145 90 3.62（3H，s），3.77（3H，s），
6.64-7.49（17H，m），7.50
（1H，s）ppm.
Ⅰ 150 90 3.59（3H，s），3.74（3H，s），
6.6-6.9（3H，m），6.9-7.7
（14H，m），7.50（1H，s）ppm.
Ⅰ 157 90 3.64（3H，s），3.79（3H，s），
6.6-7.5（11H，m），7.53
（1H，s）ppm.
Ⅰ 171 90 3.61（3H，s），3.76（3H，s），
6.6-6.8（2H，m），6.8-7.5
（10H，m），7.51（1H，s）ppm.
Table sequence number compound number frequency
（MHz）
Ⅰ 175 90 3.57（3H，s），3.73（3H，s），
6.50（1H，t），6.58（2H，d），
6.9-7.4（9H，m），7.41（1H，
s）ppm.
Ⅰ 177 90 2.25（3H，s），3.60（3H，s），
3.76（3H，s），6.4-6.6（3H，
m），6.9-7.4（9H，m），7.47
（1H，s）ppm.
Ⅰ 179 90 3.57（3H，s），3.68（3H，s），
3.72（3H，s），6.20（3H，m），
6.8-7.4（9H，m），7.42（1H，
s）ppm.
Ⅰ 180 250 3.61（3H，s），3.76（3H，s），
6.4-6.6（2H，m），6.9-7.0
（3H，m），7.07（1H，t），7.16
（1H，t），7.2-7.4（4H，m），
7.46（1H，d），7.47（1H，s）
ppm.
Ⅰ 205 60 2.11（3H，s），3.35（3H，s），
3.40（3H，s），4.71（2H，s），
6.2-7.2（12H，m），7.24
（1H，s）ppm.
Ⅰ 206 90 2.32（3H，s），3.55（3H，s），
3.7（3H，s），4.9（2H，s），
6.45-7.28（12H，m），7.40
（1H，s）ppm.
Table sequence number compound number frequency
（MHz）
Ⅰ 208 90 3.54（3H，s），3.7（3H，s），
3.77（3H，s），6.44-7.3
（12H，m），7.39（1H，s）ppm.
Ⅰ 214 90 3.56（3H，s），3.73（3H，s），
5.0（2H，s），6.5-7.65（12H，
m），7.41（1H，s）ppm.
Ⅰ 216 90 3.56（3H，s），3.69（3H，s），
5.04（2H，s），6.49-7.57
（12H，m），7.41（1H，s）ppm.
Ⅰ 217 60 3.55（3H，s），3.65（3H，s），
4.90（2H，s），7.45（1H，s），
6.4-7.5（12H，m）ppm.
Ⅰ 218 90 3.54（3H，s），3.7（3H，s），
4.9（2H，s），6.42-7.48
（12H，m），7.4（1H，s）ppm.
Ⅰ 220 60 3.40（3H，s），3.49（3H，s），
4.85（2H，s），6.2-7.5（13H，
m）ppm.
Ⅰ 230 60 3.44（3H，s），3.52（3H，s），
4.87（2H，s），6.3-7.6（18H，
m）ppm.
Table sequence number compound number frequency
（MHz）
Ⅰ 247 90 3.5（3H，s），3.61（3H，s），
5.07（2H，s），6.41-7.79
（15H，m），7.42（1H，s）ppm.
Ⅰ 248 90 3.56（3H，s），3.7（3H，s），
5.4（2H，s），6.5-8.4（15H，
m），7.42（1H，s）ppm.
Ⅰ 283 60 3.45（3H，s），3.59（3H，s），
6.5-8.0（13H，m）ppm.
Ⅰ 284 60 3.45（3H，s），3.57（3H，s），
6.3-7.8（13H，m）ppm.
Ⅰ 285 250 3.57（3H，s），3.72（3H，s），
6.55-7.78（12H，m），7.45
（1H，s）ppm.
Ⅰ 288 60 3.39（3H，s），3.52（3H，s），
6.4-7.4（10H，m），7.45（1H，
s），7.7-8.0（2H，m）ppm.
Ⅰ 290 60 2.25（3H，s），3.43（3H，s），
3.55（3H，s），6.4-7.7（13H，
m）ppm.
Ⅰ 291 90 2.43（3H，s），3.54（3H，s），
3.71（3H，s），6.5-7.68
（12H，m），7.38（1H，s）ppm.
Table sequence number compound number frequency
（MHz）
Ⅰ 295 60 3.52（3H，s），3.67（3H，s），
6.6-8.0（13H，m）ppm.
Ⅰ 296 90 3.54（3H，s），3.72（3H，s），
6.48-8.69（12H，m），7.41
（1H，s）ppm.
Ⅰ 318 60 3.59（3H，s），3.72（3H，s），
6.7-8.0（12H，m）ppm.
Ⅰ 332 90 3.48（3H，s），3.63（3H，s），
6.48-8.3（15H，m），7.34
（1H，s）ppm.
Ⅰ 333 90 3.44（3H，s），3.61（3H，s），
6.41-8.71（15H，m），7.35
（1H，s）ppm.
Ⅰ 360 250 3.55（3H，s），3.71（3H，s），
6.15（1H，s），6.48-7.39
（14H，m），7.44（1H，s）ppm.
Ⅰ 367 250 3.56（3H，s），3.70（3H，s），
6.5-6.7（2H，m），6.95（3H，
t），7.12（2H，q），7.2-7.4
（4H，m），7.45（1H，s），7.48
（1H，d）ppm.
Table sequence number compound number frequency
（MHz）
Ⅰ 368 90 3.57（3H，s），3.73（3H，s），
6.33（3H，s），6.9-7.5（14H，
m），7.46（1H，s）ppm.
Ⅰ 369 60 3.5（3H，s），3.6（3H，s），
4.1（2H，br s），6.6-7.3
（12H，m），7.43（1H，s）ppm.
Ⅰ 370 90 3.6（3H，s），3.76（3H，s），
5.24（2H，s），6.51-8.04
（13H，m），7.47（1H，s）ppm.
Ⅰ 371 400 3.60（3H，s），3.75（3H，s），
3.76（3H，s），4.95（2H，s），
6.80-6.94（6H，m），7.03
（1H，s），7.08-7.16（2H，q），
7.24-7.30（3H，m），7.49
（1H，s）ppm.
Ⅰ 373 270 3.60（3H，s），3.76（3H，s），
5.02（2H，s），6.88-6.96
（2H，d），6.98-7.40（10H，
m），7.48（1H，s）ppm.
Ⅰ 374 270 3.61（3H，s），3.76（3H，s），
5.05（2H，s），6.76-7.60
（m），7.48（s）ppm.
Table sequence number compound number frequency (MHz)
Ⅰ 376 270 3.59（3H，s），3.73（3H，s），
5.08（2H，s），6.84-6.96
（4H，m），7.04-7.40（8H，m），
7.46（1H，s）ppm.
Ⅰ 377 400 3.59（3H，s），3.75（3H，s），
3.87（3H，s），5.10（2H，s），
6.8-6.95（6H，m），7.05-7.15
（3H，m），7.22-7.30（3H，m），
7.48（1H，s）ppm.
Ⅰ 378 400 3.60（3H，s），3.75（3H，s），
5.14（2H，s），6.90-7.04
（5H，m），7.13-7.19（2H，m），
7.24-7.32（3H，m），7.47
（1H，s），7.48-7.60（2H，m）
ppm.
Ⅰ 381 270 3.59（3H，s），3.75（3H，s），
5.17（2H，s），6.75（1H，d），
6.88-7.35（11H，m），7.48
（1H，s），7.50（1H，m），7.85
（1H，d）ppm.
Ⅰ 382 400 3.60（3H，s），3.77（3H，s），
5.10（2H，s）6.94（2H，d），
7.50（1H，s），7.10-7.18
（2H，m），7.40-7.33（4H，m），
7.42（1H，t），7.48（1H，s），
7.78（1H，s），7.84（1H，d）
ppm.
Table sequence number compound number frequency (MHz)
Ⅰ 383 270 3.60（3H，s），3.72（3H，s），
4.97（2H，s），6.84-7.36
（12H，m），7.47（1H，s）ppm.
Ⅰ 384 400 3.53（3H，s），3.68（3H，s），
4.91（2H，s），6.73-7.26
（12H，m），7.40（1H，s），ppm.
Ⅰ 385 270 3.58（3H，s），3.73（3H，s），
4.95（2H，m），6.58（2H，m），
6.66（1H，d），6.86-7.35
（14H，m）ppm.
Ⅰ 386 270 3.59（3H，s），3.73（3H，s），
4.97（2H，s），6.80-6.92
（4H，m），7.0-7.32（8H，m），
7.47（1H，s）ppm
Ⅰ 387 270 3.60（3H，s），3.77（3H，d），
3.96（2H，s），6.60（1H，s），
6.70-6.90（3H，m），7.18
（2H，q），7.24-7.36（3H，m），
7.27（1H，s），7.40-7.48
（3H，m）ppm.
Ⅰ 388 400 3.60（3H，s），3.78（3H，s），
4.25（2H，d），6.68（1H，s），
6.75（1H，d），6.82（1H，d），
6.90（1H，d），7.13（4H，m），
7.27（1H，s），7.42-7.48
（3H，m），7.57（2H，d）ppm
Table sequence number compound number frequency (MHz)
Ⅰ 389 270 3.58（3H，s），3.72（3H，s），
5.08（2H，s），6.80-6.96（4H，
m），7.08-7.32（7H，m），7.46
（1H，s），7.54（1H，d）ppm.
Ⅰ 391 250 2.22（6H，s），3.65（3H，s），
3.75（3H，s），6.60-7.30
（11H，m），7.50（1H，s），ppm
Ⅰ 392 90 2.17（3H，s），2.34（3H，s），
3.55（3H，s）3.70（3H s），
6.50-7.24（11H，m），7.51
（1H，s）ppm.
Ⅰ 393 90 2.14（3H，s），2.27（3H，s），
3.59（3h，s），3.76（3H，s），
6.53-7.28（11H，m），7.50
（1H，s）ppm.
Ⅰ 394 250 2.08（6H，s），3.52（3H，s），
3.75（3H，s），6.40-7.20
（11H，m），7.50（1H，s）ppm.
Ⅰ 395 90 2.24（6H，s），3.61（3H，s），
3.77（3H，s），6.63-7.30
（11H，m）7.50（1H，s）ppm
Ⅰ 396 90 2.28（6H，s），3.60（3H，s），
3.77（3H，s），6.63-7.24
（11H，m），7.51（1H，s），ppm.
Table sequence number compound number frequency (MHz)
Ⅰ 397 270 3.58（3H，s），3.73（3H，s），
4.96（2H，s），6.80（2H，d），
6.86-6.92（2H，m），7.0-7.16
（3H，m），7.20-7.38（5H，m），
7.47（1H，s）ppm.
Ⅰ 399 270 3.60（3H，s），3.76（3H，s），
4.08（2H，s），6.80-7.58
（12H，m），7.47（1H，s），ppm
Ⅰ 400 400 3.59（3H，s），3.75（3H，s），
4.18（2H，s），6.85（2H，d），
7.00（1H，s），7.05（1H，d），
7.10-7.35（5H，m），7.48
（1H，s），8.10（2H，d）ppm.
Ⅰ 401 400 3.72（3H，s），3.88（3H，s），
4.22（2H，q），6.83（1H，s），
6.88-7.0（3H，m），7.21-7.42
（4H，m），7.50（3H，d），7.60
（1H，s），7.66（1H，m）ppm.
Ⅰ 402 400 3.70（3H，s），3.87（3H，s），
4.70（2H，s）6.80（1H，d），
6.95-7.05（3H，m），7.22-
7.48（5H，m），7.59（1H，s），
7.65（2H，s），7.92（1H，d）
ppm
Table sequence number compound number frequency (MHz)
Ⅰ 405 60 1.21（9H，s），3.42（3H，s），
3.46（3H，s），4.80（2H，s），
6.3-7.3（12H，m），7.31（1H，
s）ppm.
Ⅰ 406 270 3.57（3H，s），3.71（3H，s），
5.32（2H，s），6.92（1H，d），
7.16（2H，t），7.24-7.43（8H，
m），7.46（1H，s），7.66（1H，
d），7.76（1H，d）ppm.
Ⅰ 407 270 3.51（3H，s），3.73（3H，s），
4.59（2H，d），6.70（1H，t），
6.96（1H，d），7.08（1H，
dd），7.19（1H，d），7.22-
7.37（9H，m），7.41（1H，s），
7.48（1H，d）ppm.
Ⅰ 408 270 3.59（3H，s），3.71（3H，s），
4.29（2H，s），6.94（1H，d），
7.13-7.38（10H，m），7.45
（1H，s），7.51（1H，t），7.63
（1H，d）ppm.
Ⅰ 409 270 3.61（3H，s），3.78（3H，s），
6.99（1H，d），7.15-7.36
（4H，m），7.44（1H，t），7.50
（1H，s），7.53-7.65（2H，m），
7.78（1H，t），7.89（1H，d），
8.10-8.19（2H，m）ppm.
Table sequence number compound number frequency (MHz)
Ⅰ 410 400 3.60（3H，s），3.75（3H，s），
5.63（2H，s），6.6-7.3（12H，
m），7.47（1H，s）ppm.
Ⅰ 411 400 3.60（3H，s），3.75（3H，s），
4.8（1H，d），4.94（1H，d），
6.6-7.7（13H，m），7.47（1H，
s）ppm.
Ⅰ 412 270 1.67（3H，d），3.55（3H，s），
3.70（3H，s），5.45（1H，q），
6.5-8.1（13H，m），7.45（1H，
s）ppm.
Ⅰ 413 270 3.59（3H，s），3.73（3H，s），
5.17（2H，s），6.90-6.99
（2H，m），7.12-7.43（1H，m），
7.49（1H，s），8.08（1H，s）
ppm.
Ⅰ 414 270 3.55（3H，s），3.70（3H，s），
5.21（2H，s），6.91-7.0（2H，
m），7.10-7.19（1H，m），
7.21-7.38（9H，m），7.46
（1H，s），7.53-7.60（2H，m）
ppm.
Ⅰ 415 270 2.05（2H，m），2.78（2H，t），
3.60（3H，s），3.75（3H，s），
3.90（2H，t），6.5-7.3（13H，
m），7.48（1H，s）ppm.
Table sequence number compound number frequency (MHz)
Ⅰ 416 270 1.78（4H，m），2.65（2H，m），
3.60（3H，s），3.75（3H，s），
3.9（2H，m），6.5-7.3（13H，
m），7.47（1H，s）ppm.
Ⅰ 417 270 1.44-1.85（6H，m），2.62
（2H，t），3.60（3H，s），3.75
（3H，s），3.87（2H，t），
6.48-7.31（13H，m），7.48
（1H，s）ppm.
Ⅰ 418 270 3.61（3H，s），3.76（3H，s），
5.68（1H，s），6.8-7.6（10H，
m），7.50（1H，s），7.8（2H，
m）ppm.
Ⅰ 419 270 3.60（3H，s），3.74（3H，s），
3.89（3H，s），6.9-7.6（10H，
m），7.49（1H，s），7.9（2H，
m）ppm.
Ⅰ 420 270 3.62（3H，s），3.78（3H，s），
6.72-7.67（13H，m），7.49
（1H，s）ppm.
Ⅰ 422 270 3.62（3H，s），3.80（3H，s），
3.87（3H，s），6.72-7.48
（12H，m），7.48（1H，s），
7.78（1H，s）ppm.
Table sequence number compound number frequency (MHz)
Ⅰ 423 270 3.60（3H，s），3.70（3H，s），
4.23（4H，m），6.53-7.3
（13H，m），7.45（1H，s）
ppm.
Ⅰ 424 60 3.40（3H，s），3.50（3H，s），
6.40-8.4（15H，m），8.95
（1H，s）ppm.
Ⅰ 425 270 3.60（3H，s），3.75（3H，s），
5.40（2H，s），6.55-7.5
（13H，m），7.47（1H，s）ppm.
Ⅰ 426 90 3.53（3H，s），3.61（3H，s），
3.63（3H，s），3.66（3H，s），
4.90（2H，s），6.40-7.6
（14H，m）ppm.
Ⅰ 427 90 3.43（3H，s），3.61（3H，s），
6.4-7.4（10H，m），7.32（1H，
s），7.77（2H，d）ppm.
Ⅰ 428 90 3.55（3H，s），3.65（3H，s），
3.85（3H，s），6.7-8.0（13H，
m）ppm.
Ⅰ 443 270 3.59（3H，s），3.74（3H，s），
5.17（2H，s），6.6-7.4（14H，
m），7.47（1H，s）ppm.
Table sequence number compound number frequency (MHz)
Ⅱ 23 270 3.63（3H，s），3.74（3H，s），
6.97-7.05（3H，m），7.10
（1H，d），7.22-7.33（4H，m），
7.48（1H，d），7.49（1H，s），
8.54（2H，d）ppm.
Ⅱ 30 270 3.60（3H，s），3.74（3H，s），
6.73-7.35（8H，m），7.49
（1H，s），8.10（1H，m），8.25
（1H，m），8.38（1H，m）ppm.
Ⅱ 47 270 3.60（3H，s），3.75（3H，s），
5.52（2H，s），6.96（2H，d），
7.07-7.40（8H，m），7.49
（1H，s），7.61-7.71（2H，q）
ppm.
Ⅱ 52 60 3.51（3H，s），3.64（3H，s），
7.40（1H，s），6.5-7.8（11H，
m）ppm.
Ⅱ 53 270 3.60（3H，s），3.75（3H，s），
6.74-7.35（9H，m），7.49
（1H，s），7.88（1H，m），8.43
（1H，m）ppm.
Ⅱ 69 270 3.60（3H，s），3.75（3H，s），
6.73-7.36（9H，m），7.49
（1H，s），7.89（1H，m），8.45
（1H，m）.
Table sequence number compound number frequency (MHz)
Ⅱ 81 270 3.63（3H，s），3.78（3H，s），
5.32（2H，s），6.84-6.92
（4H，m），7.10-7.30（4H，m），
7.48（1H，s），7.98（1H，s），
8.08（1H，s）ppm.
Ⅱ 83 90 3.54（3H，s），3.65（3H，s），
6.76-7.68（12H，m），7.38
（1H，s）ppm.
Ⅱ 86 90 3.62（3H，s），3.79（3H，s），
6.8-7.5（8H，m），7.52（1H，
s）ppm.
Ⅱ 87 270 3.61（3H，s），3.76（3H，s），
6.66-6.74（2H，m），6.79
（1H，dd），7.00（1H，d），
7.16（1H，m），7.24-7.34
（3H，m），7.47（1H，s），8.47
（2H，s），8.96（1H，s）ppm.
Ⅱ 88 90 3.62（3H，s），3.76（3H，s），
4.30（3H，s），6.80-7.42
（8H，m），7.50（1H，s）ppm.
Ⅱ 90 270 3.61（3H，s），3.76（3H，s），
6.77（1H，t），6.86（2H，m），
7.04（1H，d），7.15（1H，m），
7.29（3H，m），7.48（1H，s），
8.55（2H，s）ppm.
Table sequence number compound number frequency (MHz)
Ⅱ 91 270 3.61（3H，s），3.75（3H，s），
6.77（1H，t），6.83-6.89
（2H，m），7.04（1H，d），7.15
（1H，t），7.25-7.35（3H，m），
7.48（1H，s），8.47（2H，s）
ppm.
Ⅱ 93 270 3.60（3H，s），3.75（3H，s），
3.90（3H，s），3.94（3H，s），
5.67（1H，s），6.76（1H，t），
6.84（2H，m），7.00（1H，d），
7.15（1H，m），7.25-7.32
（2H，m），7.48（1H，s）ppm.
Ⅱ 96 270 3.61（3H，s），3.75（3H，s），
6.75（1H，t），6.83（1H，
dd），6.95（1H，dd），7.07
（1H，d），7.18（1H，m），
7.29-7.37（3H，m），7.49
（1H，s）ppm.
Ⅱ 97 Proton-decoupled Carbon -
13 n.m.r.at 67.7 MHz：
delta 51.25，61.59，106.54，
107.41，110.85，114.96，
115.45，119.58，123.72，
125.06，128.90，130.05，
132.41，152.29，153.57，
158.81，160.03，160.13，
160.22，167.49，169.95 ppm.
Table sequence number compound number frequency (MHz)
Ⅱ 98 270 2.72（3H，s），3.60（3H，s），
3.77（3H，s），5.08（2H，s），
6.5-7.4（9H，m），7.48（1H，
s）ppm.
Ⅱ 99 270 3.60（3H，s），3.74（3H，s），
5.50（2H，s），6.92-7.0（2H，
m），7.09-7.36（9H，m），7.47
（1H，s），7.50（1H，d）ppm.
Ⅱ 100 270 3.60（3H，s），3.75（3H，s），
5.33（2H，s），6.90-6.96
（2H，m），7.06-7.18（3H，m），
7.24-7.34（3H，m），7.49
（1H，s），8.07（1H，d），8.14
（1H，d），8.28（1H，s）ppm.
Ⅱ 101 270 3.60（3H，s），3.75（3H，s），
5.31（2H，s），6.90-6.99
（2H，m），7.06（1H，s），
7.10-7.18（2H，m），7.25-
7.34（3H，m），7.49（1H，s），
8.17（2H，s）ppm.
Ⅱ 102 270 3.60（3H，s），3.75（3H，s），
5.50（2H，s），6.89-6.99
（3H，m），7.1-7.42（7H，m），
7.49（1H，s），7.62（1H，t），
7.71（1H，d），7.83（1H，d），
8.0（1H，d）ppm.
Table sequence number compound number frequency (MHz)
Ⅱ 103 270 3.60（3H，s），3.77（3H，s），
5.49（2H，s），6.90-6.98
（2H，m），7.0（1H，d），7.08-
7.20（3H，m），7.24-7.33
（3H，m），7.39（1H，d），7.49
（1H，s）ppm.
Ⅱ 104 270 3.44（3H，s），3.70（3H，s），
5.09（2H，s），6.82（2H，d），
6.90（1H，s），7.0-7.14（4H，
m），7.16-7.36（3H，m），7.49
（1H，s），8.05（2H，d）ppm.
Ⅱ 105 270 3.60（3H，s），3.75（3H，s），
5.38（2H，s），6.82-6.98
（3H，m），7.05-7.20（3H，m），
7.20-7.35（3H，m），7.48
（1H，s），7.78（1H，d），8.43
（1H，s）ppm.
Ⅱ 106 270 3.60（3H，s），3.76（3H，s），
6.74-7.38（9H，m），7.48
（1H，s），7.98（1H，m），8.30
（1H，m）ppm.
Ⅱ 107 270 3.60（3H，s），3.76（3H，s），
6.75-7.37（9H，m），7.49
（1H，s），8.45（1H，m），9.03
（1H，m）ppm.
Compile sequence number compound number frequency (MHz)
Ⅱ 270 270 3.61（3H，s），3.78（3H，s），
6.28（1H，m），6.70（2H，m），
6.9-7.5（9H，m），7.48（1H，
s），9.55（1H，br，s）ppm.
Ⅱ 271 270 3.60（3H，s），3.74（3H，s），
6.74-7.39（9H，m），7.50
（1H，s），8.32（1H，m）ppm.
Ⅱ 272 270 2.32（3H，s），2.54（3H，s），
3.60（3H，s），3.76（3H，s），
6.72-7.35（8H，m），7.49
（1H，s），8.00（1H，s）ppm.
Ⅱ 273 270 3.60（3H，s），3.72（3H，s），
6.72-7.36（8H，m），7.50
（1H，s），8.26（2H，m）ppm.
Ⅱ 274 270 3.60（3H，s），3.75（3H，s），
4.04（3H，s），6.74-7.36
（10H，m），7.50（1H，s）ppm.
Ⅱ 310 270 3.60（3H，s），3.75（3H，s），
5.30（2H，s），6.72（1H，d），
6.87-7.35（9H，m），7.43
（1H，t），7.49（1H，s）ppm.
Ⅱ 311 270 Data in common for both
regioisomers：3.60（3H，
s），3.77（3H，s），5.38（2H，
Table sequence number compound number frequency (MHz)
s），6.90-7.18（5H，m），
7.23-7.33（3H，m），7.49
（1H，s）ppm.Data for
major isomer：6.70（1H，
d），8.32（1H，d）ppm.Data
for minor isomer：6.98
（1H，d），8.38（1H，d）ppm.
Ⅱ 315 270 3.39（3H，s），3.60（3H，s），
3.73（3H，s），3.84（3H，s），
5.63（1H，m），5.85（1H，m），
6.59（1H，m），6.7-7.3（8H，
m），7.47（1H，m）ppm.
Ⅱ 8 270 3.60（3H，s），3.75（3H，s），
6.62-7.36（10H，m），7.48
（1H，s），8.38（2H，m）ppm.
Ⅱ 15 270 3.60（3H，s），3.74（3H，s），
6.62-7.36（10H，m），7.48
（1H，s），8.45（2H，m）ppm.
Ⅱ 35 270 3.60（3H，s），3.74（3H，s），
6.70-7.50（10H，m），7.49
（1H，s），8.92（1H，m）ppm.
Ⅱ 313 270 2.38（3H，s），2.41（3H，s），
3.59（3H，s），3.75（3H，s），
6.29（1H，s），6.75（1H，t），
6.84（2H，t of d），6.98
（1H，d），7.15（1H，t），
Table sequence number compound number frequency (MHz)
7.25-7.34（3H，m），7.48
（1H，s）ppm.
Ⅱ 319 270 2.90（6H，s），3.60（3H，s），
3.77（3H，s），6.18（1H，d），
6.75-7.37（8H，m），7.48
（1H，s），8.22（1H，d）ppm.
Ⅱ 320 270 Data in common for both
regioisomers：3.61（3H，s），
3.74（3H，s），7.50（1H，s）
ppm.Data for major
isomer：2.35（3H，s）ppm.
Data for minor isomer：2.38
（3H，s）ppm.
Ⅲ 23 270 3.65（3H，s），3.75（3H，s），
4.97（2H，s），6.75-6.87（3H
m），7.14（1H，t），7.21-7.40
（9H，m），7.49（1H，s）ppm.
Ⅲ 51 270 3.61（3H，s），3.73（3H，s），
6.75-6.82（2H，m），7.02-
7.17（2H，m），7.22-7.38
（3H，m），7.46（1H，s），
7.47-7.59（4H，m），7.62-
7.72（1H，m），7.80（1H，d）
ppm.
Ⅲ 131 270 3.63（3H，s），3.74（3H，s），
6.80（1H，d），6.86（1H，s），
Table sequence number compound number frequency (MHz)
6.99（2H，d），7.15-7.37
（6H，m），7.48（1H，s），7.46
（1H，d），7.93（1H，d）ppm.
Ⅲ 212 270 3.65（3H，s），3.77（3H，s），
5.08（2H，s），6.74-6.80
（2H，m），6.85-6.89（1H，d），
7.16（1H，t），7.20-7.38
（4H，m），7.49（1H，s），7.54
（2H，d），8.21（2H，d）ppm.
Ⅳ 87 270 3.64（3H，s），3.75（3H，s），
6.80（1H，d），6.86（1H，s），
7.03（1H，d），7.21-7.38
（4H，m），7.47（1H，d），7.48
（1H，s），8.44（2H，s），8.95
（1H，s）ppm.
The compound of general formula of the present invention (I) can prepare with several different methods, and some method is described in VIII in the schematic diagram I.By these schematic diagrames, defined term Z, X, A, B, E, K, R 1, R 2, R 3, R 4And R 5, R 6Be hydrogen or a kind of metal (for example sodium or potassium), R is an alkyl, and L is a leaving group, halide (chloride, bromide or iodide) for example, CH 3SO - 4Anion or sulfonyloxy anion.Under suitable temperature and The suitable solvent in or do not have under the situation of solvent, finish the schematic diagram I to the described multiple conversion of VIII.
The schematic diagram I has illustrated the whole bag of tricks, and wherein the 'beta '-methoxy acrylic acid carbomethoxy is to be formed in the final step of preparation The compounds of this invention by the precursor of preformed three aromatic ring frame structures.Or at the initial stage of preparation feedback formation 'beta '-methoxy acrylic acid carbomethoxy, in this case, the other parts that final step or a few step comprise The compounds of this invention are processed to form three aromatic ring frame structures.The example of this method is represented to VIII with the schematic diagram III.
No matter press which kind of order, reactions steps always proceeds to and makes compound of the present invention, can be prepared as all compounds of the present invention common hexichol ehter bond or thioether bond by a kind of coupling reaction shown in the schematic diagram II.For the synthetic comment of Ullmann ether referring to A.A.Moroz and M.S.Shrartsberg, Russian Chem, Reviews, 1974,43,679.Also visible D.Hands, H.Marley, S.J.Skittrall, S.H.B.Wright and T.R.Verhoeuen, J.Heterocyclic Chem., 1986,23,1333.Usually finish these coupling reactions in the presence of catalyzer, this catalyzer is by the salt or the compound of transition metal or transition metal, as copper, and perhaps mantoquita or copper compound, or their mixture is formed.In the schematic diagram II, W represents Z-X-group (the wherein definition of Z and X such as above-mentioned), represents that perhaps the standard method described in the available Chemistry Literature is transformed into a kind of group of Z-X-group; For example W can be-OH ,-SH or-NHR 4Y represents the 'beta '-methoxy acrylic acid carbomethoxy of α-connection in the The compounds of this invention, represents that perhaps standard method described in the available Chemistry Literature and/or schematic diagram I and the described method of following each section are transformed into a kind of group of this group, and for example Y can be-CH 2COOH ,-CH 2COOMe or-CHO.In the schematic diagram II, L is halogen preferably.Therefore under the Ullmann reaction condition of having narrated, the reaction of the compound of the compound of general formula (XI) and general formula (XII) obtains the intermediate of general formula (VIII).As an example of the coupling reaction shown in the schematic diagram II, the 3-phenoxy group phenol that replaces, as its salt, with 2-bromine or the coupling of 2-chlorophenylacetic acid salt, after acidifying, obtaining the 2-(3-phenoxy group phenoxy group that replaces) phenylacetic acid is (for example, referring to GB2078-743, Ihara Chem.Ind., on June 27th, 80).Another kind method is under the Ullmann reaction condition of having narrated, compound prepared in reaction general formula (VIII) intermediate of the compound of general formula (IX) and general formula (X).
Under a kind of concrete condition, the present invention is the method for the compound of preparation general formula (I), this method is included in alkali and exists down, general formula (XII compound and general formula (XI phenol or thiophenols reaction a) a), or be preferably in the catalyzer existence down, (XII compound a) and the reactant salt of phenol or thiophenols, this catalyzer contains suitable transition metal to general formula, transition metal salt or compound or their mixture.
Figure 881072702_IMG69
Y in the formula 1It is halogen
Figure 881072702_IMG70
The compound of general formula of the present invention (I) can be made by the phenylacetic acid ester of general formula (III) or the ketone ester of general formula (VI) by the step shown in the graphic I.
Compound available bases of general formula (I) (for example sodium hydride or sodium methoxide) and methyl formate are handled the phenylacetic acid ester and are made.If a kind of molecular formula CH 3L(is L definition as above-mentioned wherein) compound be added in the reactant mixture, then can obtain the compound of general formula (I).If Protic acid is added in the reactant mixture, can obtain the compound (R wherein of general formula (II) 6Be hydrogen).Another kind method is to isolate the compound of general formula (II), R in the formula from reactant mixture 6Be metal (for example sodium).
Available a kind of general formula is CH 3L(is the definition of L such as above-mentioned wherein) compound treatment, with the compound (R in the formula of general formula (II) 6Be metal) be transformed into the compound of general formula (I).Available bases (for example sodium carbonate) and a kind of general formula CH 3The compound of L is handled one by one, with the compound (R in the formula of general formula (II) 6Be hydrogen) be transformed into the compound of general formula (I).
Another kind method is under acidity or alkali condition, and cancellation methyl alcohol prepares the compound of general formula (I) from the acetal of general formula (IV).Spendable reactant of this transformationreation or reactant admixture are the diisopropyl amide lithiums, potassium acid sulfate (for example, see T Yamada, H Hagiwara and H Uda, J.Chem.Soc., Chemical Communications, 1980,838 reach list of references wherein), and triethylamine, usually for example (for example carry out in the presence of the titanium tetrachloride at lewis acid, see K Nsunda and L Heresi, J.Chem.Soc., Chemical Communications, 1985,1000).
At lewis acid for example in the presence of the titanium tetrachloride, the methyl silicane ethyl ketene acetal (wherein R is an alkyl) of handling general formula (V) with trimethyl orthoformate can prepare the acetal of general formula (IV) and (see K Saigo, M Osaki and T Mukaigama, Chemistry Letters, 1976,769).
With alkali and general formula R 3SiCl or R 3The trialkylsilkl halide of SiBr, for example trimethylsilyl chloride is perhaps used alkali (for example triethylamine) and general formula R 3Si-OSO 2CF 3The trialkylsilkl trifluoride handle, the methyl silicane ethyl ketene acetal that can prepare general formula (V) from the phenylacetic acid ester of general formula (III) (for example, is seen C Ainsworth, F Chen and Y KuO, J.Organometallic Chemistry, 1972,46,59).
Usually needn't separation of intermediates (IV) and (V), under suitable condition, by adding above-named suitable reactions agent one by one, can prepare the compound of general formula (I) by the phenylacetic acid ester of general formula (III) with " single still method ".
Another kind method, with methoxyl group methylenation reactant, methoxyl group methylene tri phenyl phosphorane for example, handle the ketone ester of general formula (VI), the compound that can prepare general formula (I) (for example, is seen W Steglich, G Schramm, T Anke and F Oberwinkler, EP on July 4th, 0044448,1980).
Method described in the available document prepares the ketone ester of general formula (VI).Useful especially method comprises: (I) uses L M Weinstock, R B Currie and A V Lovell, Synth.Commun., 1981,11,943 and list of references wherein described in method, with suitable phenyl magnesium halide or phenyl lithium and the reaction of dimethyl grass ester; (II) is usually solvent-free, under the temperature more than 100 ℃, with the phenylacetic acid ester of selenium dioxide oxidation general formula (III); (III) for example uses magnesia oxidation mandelate in suitable solvent.
Many other method preparations described in the also available Chemistry Literature of the corresponding phenylacetic acid of the phenylacetic acid ester of general formula (III) and general formula (VII).For example, with D C Atkinson, K E Godfreg, B Meek, J F Saville and M R Stillings, J.Med.Chem., 1983,26,1353 and D C Atkinson K E Godfrey, P L Megers, N C Rhillips, M R Stillings and A P Welbourn, J.Med.Chem., several effective methods of narration in 1983,26,1361.Use suitable precursor (wherein the phenoxy group substituting group and the substituting group E of ortho position replacement exist), by J-P Rieu, A Boucherle, H Cousse and G Mouzin, Tetrahedron, 1986,42, many methods of preparation 2-arylprop acid esters described in 4095 and acid also can be used for preparing the phenylacetic acid ester of general formula (III) and the phenylacetic acid of general formula (VII).
Figure 881072702_IMG71
The schematic diagram III, IV, V, VI and VII illustrate the intermediate that contains first 'beta '-methoxy acrylic acid carbomethoxy with diagram, and show they are how to be transformed into some true-to-shape of The compounds of this invention (I).
The explanation of schematic diagram III is in the presence of alkali, sometimes at transition metal or transition metal salt catalyst, for example copper or copper salt catalyst exist down, the compound of general formula (X III) and the reaction of following compound obtain the compound of general formula (X IV), these compounds are that the virtue of general formula ZL belongs to or assorted virtue belongs to compound, and wherein the definition of Z and L as mentioned above; Or general formula Z 2I +T -Salt compounded of iodine, wherein the definition of Z as mentioned above, T -Be counter ion, halide ion for example; Or aryl or heteroaryl bismuth.In addition, in the presence of alkali, the compound of general formula (VIII) and general formula ZSO 2The aryl of Q or heteroarylsulfonyl halide (wherein the definition of Z as mentioned above, Q is a halogen) reaction obtains the compound of general formula (X V).Also have, in the presence of alkali, the compound of general formula (X III) also can with general formula ZCHR 1The aryl alkyl of L or heteroaryl alkyl compound (Z wherein, R 1With the definition of L as mentioned above) reaction, obtain the compound of general formula (X VI).
Schematic diagram (IV), generally in the presence of alkali, according to shown in the schematic diagram III with the corresponding similar reactive mode of phenol of general formula (X III), the mercaptan of general formula (X VII) virtue with general formula ZL is belonged to or assorted virtue genus compound, perhaps with general formula Z 2I +T -Salt compounded of iodine, perhaps with the reaction of aryl or heteroaryl bismuth, obtain the compound of general formula (X VIII).Similarly, in the presence of alkali, the mercaptan and the general formula ZCHR of general formula (X VII) 1The aryl alkyl of L or heteroaryl alkyl compound react, and obtain the compound of general formula (X IX).The sulphur compound of general formula (X VIII) and (XI X) can be oxidized to corresponding sulfoxide or sulfone with the standard method described in the Chemistry Literature.
The schematic diagram V, the compound of general formula (XX) in the presence of alkali, reacts the compound of formation general formula (X XI) with the virtue genus of general formula ZOH or the hydroxy derivatives (wherein the definition of Z as mentioned above) of assorted virtue genus compound usually.In addition, the compound of general formula (XX) and general formula P(OR) 3Inferior microcosmic salt of trialkyl or formula M +P -(O) (OR) 2The compound reaction of (wherein the definition of R as mentioned above, M is a metal, for example sodium or lithium) obtains the phosphonate ester of general formula (X XII).The phosphonate ester of general formula (X XII) is in the presence of alkali, with general formula ZR 1C:O(is Z and R wherein 1Definition as mentioned above) aldehydes or ketones reaction, obtain the alkene of general formula (XX IV).In addition, the aldehydes or ketones of general formula (XX III) is used general formula ZR 1C -P(O) (OR) 2M +(Z in the formula, R, R 1With the definition of M as mentioned above) the phosphonate ester anionic treatments, perhaps handle with corresponding phosphorane, also can obtain the alkene of general formula (XX IV).The alkene of general formula (XX IV) is reduced into the compound of general formula (XX V) by the appropriate catalyst hydrogenation reaction.
The schematic diagram VI, the compound of general formula (XX VI), in the presence of alkali, with the definition of Z and Q in the general formula ZCOQ(formula as mentioned above) the acyl halide reaction, perhaps in the presence of suitable dehydrating agent, with general formula ZCO 2The definition of Z is as mentioned above in the H(formula) acid reaction, obtain the compound of general formula (XX VII).
The intermediate of general formula (XX VI) also can use the method described in the Chemistry Literature, is transformed into the compound of other type of general formula of the present invention (I).For example, R in the general formula (XX VI) 4Be the compound of hydrogen, can be transformed into corresponding sulfonic acid chloride (referring to Qrganic Synthesis, 1981,60,121), in the presence of alkali, handle then, change sulphonic acid ester with alcohol or phenol by diazotization.
In the general formula of the present invention (I) at least one of A and B be the compound of hydrogen, by the method that the electrophilic described in the Chemistry Literature replaces, can being transformed in the general formula (I) at least, one of A and B are the compound of certain substituting group (for example hydrogen or nitro or acyl group).
General formula (X III), (X VII), (XX), the intermediate of (XX III) and (XX VI) can use method described in the Chemistry Literature and graphic I and the described method of II to prepare.For example, L is that the compound of bromine can be the compound of H by L in the general formula (XX) in the general formula (XX), and in light radiation or do not have under the condition of light radiation, with N-bromosuccinimide or N, N-two bromos-dimethyl hydantion reaction makes.
General formula (IX), (X), (XI), (XII), ZL, Z 2T +T -, ZCHR 1L, ZSO 2Q, ZOH, ZR 1C:O, ZR 1C -P(O) (OR) 2M +, ZCOQ and ZCO 2The intermediate of H can prepare with the method for narrating in the Chemistry Literature.
Figure 881072702_IMG73
Figure 881072702_IMG74
Figure 881072702_IMG76
In the schematic diagram VII, for example can use two chromic acid pyridines (for example carrene) or oxalyl chloride in suitable solvent in dimethyl sulfoxide (DMSO), in the presence of alkali, the compound oxidation of general formula (XX VIII) to be become the aldehyde (R in the formula of general formula (XX III) 2Be H) or ketone (R in the formula 2Be alkyl).The aldehydes or ketones of general formula (XX III) can with general formula ZONH 2Or ZCHR 1ONH 2Hydroxylamine reaction, or with general formula ZNR 1NH 2(Z and R in the formula 1Definition as mentioned above) hydrazine reaction, obtain the compound of general formula of the present invention (I), X is respectively ON=CR in the formula 2, CHR 1ON=CR 2Or NR 1N=CR 2Group.The compound of general formula (XX III) also can with general formula ZMgHal or ZCHR 1Hal is a chlorine in the MgHal(formula, bromine or iodine, Z and R 1Definition as mentioned above) that reagent reacting of Green, obtain the compound of general formula I of the present invention, X is respectively CR in the formula 2(OH) or CHR 1CHOH.In the presence of reductant (for example hydrogen boronation cyanogen sodium or hydrogen) and suitable metallic catalyst, the compound of general formula (XX III) also can with general formula ZNHR 10(definition of Z as mentioned above and R in the formula 10Be hydrogen or C 1-4Alkyl) a kind of amine reacts, and generates a kind of compound of general formula of the present invention (I), and X is NR in the formula 10CHR 2When removing reductant and working as R 10During for H, the back reaction can obtain the compound of general formula of the present invention (I) immediately, and X is N=CR in the formula 2Perhaps as application formula ZCHR 1ONH 2Shi Zewei CHR 1ON=CR 2
Use Jones reagent (chromium trioxide in sulfuric acid), R in the formula 2Can be oxidized to the carboxylic acid of general formula (XX IX) for the compound of the general formula (XX VIII) of H.In suitable solvent, use known a kind of standard coupling agent in the document, for example dicyclohexyl carbodiimide or diimidazole carbonyl, this carboxylic acid (XX IX) can directly be transformed into the compound of general formula of the present invention (I), and X is O in the formula 2C, CHR 1OCO, SCO, CHR 1SCO, NR 4CO or CHR 1NR 4CO.
Another kind method is handled with for example thionyl chloride or oxalyl chloride, and the carboxylic acid of general formula (XX IX) can be transformed into the acid chloride of general formula (XXX).Alkali exists down, in suitable solvent, the acid chloride of general formula (XXX) can with general formula ZOH, ZCHR 1OH, ZSH, ZCHR 1SH, ZNR 4H or ZCHR 1NR 4The compound of H reacts, and obtains the compound of general formula of the present invention (I), and X is respectively O in the formula 2C, CHR 1CO, SCO, CHR 1SCO, NR 4CO or CHR 1NR 4CO.
The compound of general formula (XX VIII), in the alkali existence or not, also can be directly and the reaction of the compound of general formula ZL, Z be that active virtue belongs to base (as nitrobenzophenone) or assorted virtue belongs to basic (as 2-pyridine or 2-pyrimidine radicals) in the formula, obtains the compound of general formula (X XI).Must produce the oxygen anion of the compound of general formula (XX VIII) earlier with highly basic (as sodium hydride) reaction.
In addition, in the presence of acid acceptor, with for example thionyl chloride or phosphorus tribromide processing (when L in the formula is chlorine or bromine) of halogenating agent, perhaps use sulfonic acid halide (to handle as paratoluensulfonyl chloride, when L is sulfonyloxy), the compound of general formula (XX VIII) can be transformed into the compound of general formula (XX).Then, the compound of general formula (XX) also can be employed shown in the schematic diagram V.In addition, when L is halogen, they can with general formula Z(R 5) 2R in the P(formula 5Definition as mentioned above) phosphine reaction, be transformed into the compound of general formula of the present invention (I), X is (R in the formula 5) 2P +CHR 2Q -These compounds can be one by one and alkali and general formula ZCOR 1(Z and R in the formula 1Definition as mentioned above) carbonyls reaction, obtain the alkene of general formula (XX IV).
The schematic diagram VIII intermediate of the general formula (VIII) shown in the marginal data schematic diagram II, wherein W is any group that can be transformed into ZX-, Y is any group that can be transformed into the 'beta '-methoxy acrylic acid carbomethoxy.
Use general formula (XI) the compound reaction described in detail in the schematic diagram II general Ullmann coupling condition, the compound of general formula (XX XI) can with the compound reaction of general formula (XX XII), obtain the compound of general formula (XXX III).The acid of general formula (XXX III) can be reacted the methyl ester that is transformed into general formula (XXX IV) with methyl alcohol in the presence of acid (example hydrochloric acid).Then, the compound of general formula (XXX IV) can be transformed into the 'beta '-methoxy acrylic acid methyl esters of general formula (XX VIII) with the method that is described in detail in the schematic diagram I.
Also have, use the acrylate described in the schematic diagram VII to be transformed into general formula (XX III) about general formula (XX VIII), (XX), (XX IX), the method of the compound of (XXX) and (I) can be transformed into the intermediate of general formula (XXX IV) general formula (XXX VIII), (XXX V), (XXX VI), the intermediate of (XXX VII) and (III).The compound of general formula (III) can be transformed into the compound of the general formula shown in the schematic diagram I (I).
Figure 881072702_IMG77
On the other hand, the invention provides the method for preparing molecular formula (I) compound described in the literary composition, and provide molecular formula (II) to (VII), (X III) to (XXX) and (XXX III) is to the intermediate of (XXX VIII).
These compounds are effective bactericide, can be used for controlling one or more following cause of diseases: the rice blast downy midew of rice of rice; The wheat leaf rust of wheat, yellow rust and other rust, the leaf rust of barley of barley, yellow rust and other rust, the rust of plant is tasted in other hosta such as coffee, pears, apple, peanut, vegetables and other sight; Other powdery mildew on powdery mildew of wheat and barley of barley and wheat (powdery mildew (Powderymildew)) and the various hosta, the smut of hop for example, melon belongs to the red bean powdery mildew of (as cucumber), the apple mildew of apple and grape powdery mildew; The length of the cereal spore of wriggling is mould, chews the mould genus of spore, the mould genus of septoria musiva, Pseudocercosporella herepotrichoides and Gaeumannomyces graminis; The cercospora brown spot of peanut on the peanut and the cercospora leaf spot of groundnut, the tail spore of other hosta such as beet, banana, soybean and rice is mould; Tomato, grass is mould, vegetables, the tomato gray mold (grey mould) of grape and other Hosta; Vegetables (as cucumber), rape, apple, the interlink spore genus on tomato and other Hosta; Apple scab on the apple; The mould frost of grape on the grape is sick; Other downy mildew such as downy mildew of lettuce on the lettuce; Soybean, tobacco, the downy mildew on onion and other Hosta; The false downy mildew of hop and the cucumber downy mildew of Cucurbita; The potato late blight of potato and tomato; Vegetables, grass is mould, pear, pepper is seen and tastes plant, tobacco, the cotton boll blight of coconut palm and other Hosta; Thanatephorus cucumeris on the rice and other Hosta such as wheat and barley, vegetables, the Rhizoctonia on cotton and the meadow.
Some compound has very wide field of activity to the fungi on the plant corpus, disease harvest time of various Hostas such as fruit also had activity (the citrus edge mildew on the orange for example, scutellum rot of orange and Trichoderma Viride, banana anthracnose dish garden spore on the banana and the grape grey mould on the grape).
And some compound is effectively to seed selection, to all kinds of fusariums, the mould genus of septoria musiva, Tilletia (Tilletia foetida, a kind of wheat seed seedbed disease), Ustilago, Helminthosporium, cotton seedling blight of cotton and the rice blast of rice are effective.
These compounds are systematic scope of activities in plant, and is volatile, is highly effective to plant epiphyte in gas phase.
The compound of many general formulas (I) comprises that X in the formula is those compounds of 0, and is more safer than the allied compound of known structure to some crops (as vine).
The invention provides a kind of fungicidal method, this method comprises the compound mentioned above of effective dose or the composition that contains it is applied to plant, the seed of plant, the perhaps location of plant or seed.
These compounds also can be used as industry (corresponding with agricultural) bactericide, for example prevent fungus attack wood, green hide, leather, particularly paint film.
These compounds can be directly used in the sterilization purpose, but more suitably are to be mixed with composition with carrier or thinner.Therefore, the invention provides a kind of bactericidal composition, said composition contains compound and the sterilization acceptable carrier or the thinner of general formula defined above (I).
During as bactericide, these compounds can be used with many modes.For example, form that they can be prepared or not preparation directly applies to the leaf of plant, in other medium of the plant that seed or the plant of planting or preparation will be planted, they can spraying, dustings or are made into emulsion or paste uses, and can use their steam or discharge granule slowly.Can be applicable to any part of plant, comprise leaf, stem, branch or root, perhaps be applied to root soil on every side, the seed before perhaps being applied to plant perhaps is applied to general soil, paddy field water either or solution bacterial culture system.Also can use electric atomizing technology or other low capacity method, be injected into The compounds of this invention in the plant or be sprayed on the vegetables.
Term used herein " plant " comprises seedling, shrub and tree.And method for disinfection of the present invention comprises prevention, protection and eradicates and handle.
Be used for agricultural and gardening purpose, these compounds preferably use with the form of composition.Under any circumstance, the type of composition therefor all is decided by the specific purpose estimated.
Composition can dust form or particle form use, these dust and particle contain effective ingredient (compound of invention) and diluent or carrier, kaolin for example, bentonite, diatomite (Kiesselguhr), dolomite, calcium carbonate, talcum, powder magnesia, Fuller soil, gypsum, diatomite (Diatomaceous) and potter's clay.Make the particle that is fit to be applied to soil in advance, do not need further processing.Available active ingredient dipping filler powder is perhaps made ball to the mixture of active ingredient and powder filler, to make particle.The composition of seed selection usefulness can contain a kind of additive (as mineral oil), helps the bonding of composition and seed, perhaps uses organic solvent (as N-Methyl pyrrolidone, propane diols or dimethyl formamide) to be modulated to seed selection purpose active ingredient.Composition can be the moistening powder type that contains the water dispersible granular of wetting agent or dispersant, is beneficial to the dispersion in liquid.Powder and particle also can contain filler and suspending agent.
Active ingredient is dissolved in the organic solvent that contains wetting agent or emulsifier, then mixture is added in the water that contains wetting agent or emulsifier, make emulsible concentrate or emulsion.Appropriate organic solvent is that virtue belongs to solvent, as alkylbenzene and Fluhyzon; Ketone, isophorone for example, cyclohexanone and methyl cyclohexanone; Chlorated hydro carbons is as chlorobenzene and trichloroethanes; And alcohols, as benzyl alcohol, furfuryl alcohol, butanols and glycol ether.
Basically insoluble solid suspension concentrate carries out ball milling with dispersant and the suspending agent that stops the solid sedimentation or the bead mill is made.
Being used for sprayed composition can be aerosol form, under pressure, in the presence of propellant such as fluoro trichloromethane or dicholorodifluoromethane, prescription is packed in the container.
Compound of the present invention can dry state mix with firework mixture, and formation can produce the composition of the smog that contains compound in confined space.
Another kind method, compound can microencapsulation form be used, and they are formulated in the biological degradation polyalcohol prescription, make that working substance mass-energy is controlled slowly to be discharged.
Contain suitable additive, for example improve distribution, bonding force and prevent from treatment surface, to drop down next additive, make different compositions can be applicable to various uses better.
Compound of the present invention can mix use (for example containing nitrogen, the chemical fertilizer of phosphorus or potassium) with fertilizer.The composition that only contains the chemical fertilizer granule that mixes (for example with the method that clads) this compound is best.Such particle can contain the compound up to 25% weight.Therefore the present invention also provides a kind of the have compound of chemical fertilizer and general formula (I) or the fertilizer composition of its salt or metal complex.
Wettable powder, emulsifiable concentrate and suspension-concentrates contain surfactant usually, wetting agent for example, dispersant, emulsifier or suspending agent, these reagent can be cationic, and be anionic or non-ionic.
Suitable cationics is the season ammoniate, for example cetyl front three ammonia bromide.Suitable anionics are soap classes, sulfated fatty belongs to monoesters (as lauryl sodium sulfate) and the sulfonic acid virtue belongs to the salt of compound (as neopelex, sodium lignosulfonate, calcium or ammonia, dibutyl naphthalene sulphonic acid ester and a kind of diisopropyl-and the mixture of triisopropyl-sodium naphthalene sulfonate).
Suitable nonionics is the condensation product of oxirane and fatty alcohol such as oleyl alcohol or hexadecanol, or the condensation product of oxirane and alkyl phenol such as octyl phenol or nonyl phenol and octyl cresol.Another kind of nonionics is the part ester of being derived by long-chain fatty acid and hexitan, the condensation product of described part ester and oxirane, and lecithin.Suitable suspending agent is hydrophilic colloid (as polyvinylpyrrolidone and sodium carboxymethylcellulose) and swelling clay such as bentonite or atlapulgite.
Composition as aqueous dispersions or emulsion use uses with the concentrate form that contains high active ingredient usually, this concentrate of dilute with water before using.The best ability long term storage of these concentrates after the storage, keeps uniform water formulation in order to be formed in long enough in the time, dilutable water is used its available common sprayer unit.This concentrate contains usually up to 95% weight active ingredient, and 10-85% is comparatively suitable, for example 25-60% weight.After being diluted to water formulation, application target on the estimation, content of effective is transformable in the water formulation, can use the water formulation that contains 0.00055 or 0.01% to 10% weight active ingredient.
Composition of the present invention can contain other compound of biologically active, for example has the compound of similar or complementary bactericidal activity, perhaps makes plant have the compound of growth regulating, deweeding or insecticidal activity.
The Fungicidal compounds that exists in the composition of the present invention is such compound, it can eliminate cereal (as wheat) fringe disease, the mould genus of septoria musiva for example, Gibberella and Helminthosporium, can eliminate the disease of seed seedbed and soil base soil, mould and the white powdery mildew of originality on the grape, the white powdery mildew on the apple and scar or the like.After containing another kind of bactericide, said composition has wideer field of activity than the compound of single general formula (I).And the bactericidal activity of this another kind bactericide mutual-through type (I) compound has synergy.The example that can be included in the Fungicidal compounds in the present composition is as follows: carbendazim, benomyl, thiophanate methyl, thiabendazole, furidazol, Grandox fumigant, Euparen, Cymoxanil, Oxadixyl, Ofurace, metalaxyl, furalaxyl, benalaxyl, fosetyl-aluminium, nuarimol, iprodione, prothiocarb, the agent of diformazan sclerotium, the agent of ethene sclerotium, Penconazole, myclobutanil, propionamide, diniconazole, the phonetic phosphorus of pyrrole, the phonetic phenol of second is detested bacterium phosphorus, tridemorph, triforine, nuarimol, triazbutgl, seed-grain is fixed, and 1,1 '-triacetate of imino group (octyl group methylene) two guanidines, fourth Saite, propiconazole, prochloraz, flutriafol, hexaconazole, (2RS, 5RS)-5-(2, the 4-dichlorophenyl) tetrahydrochysene-5-(1H-1,2,4-triazol-1-yl methyl)-2-furyl-2,2,2-trifluoroethyl ether, Cyproconazole, terbuconazole, pyrrolnitrin, 1-((2RS, 4RS; 2RS, 4RS)-4-bromo-2-(2, the 4-dichlorophenyl) tetrahydrofuran base)-1H-1,2; the 4-triazole, 5-ethyl-5,8-dihydro-8-oxo (1; 3)-Er Evil cyclopentadienyls-(4,5-g) quinoline-7-carboxylic acid, (RS)-1-aminopropyl phosphonic acids; 3-(2, the 4-dichlorophenyl)-2-(1H-1,2; the 4-triazol-1-yl) quinazoline-4(3H)-～, fluzilazole, triazolone; Triadimenol, diclobutrazol, butadiene morpholine; Pyrifenox, fenpropidin, Chlorozolinate; press down mould azoles, first furan anilide, carboxin; oxycarboxin, methfuroxam, dodemorph; BAS454, blasticidin-S S, kasugarnycin; Hinosan, kitazine P, cycloheximide; Rabcide, probenazole, Fujione; tricyclazole, 4-chloro-N-(cyano group (ethyoxyl) methyl) benzamide, Pyroquilon; Chlorbenzthiazone, neoasozin, Polyoxin D; validamycin A, happy rust amine, flutolanil; Pencycuron, diclomezine, phenazine oxide; Sankel, techlofthalam, Bitertanol; the phonetic fen sulphonic acid ester of second, etaconazole is disliked mould spirit; streptomycin, Cyprofuram, Bitertanol; quinomethionate, dimethirimol, 1-(2-cyano group-2-methoxyl group acetimidoyl)-the 3-ethyl carbamide; fenapanil, tolelofos-methyl, chlorine pyrrole furan ether; Carbatene, maneb, mancozeb; difoltan, tpn, anilazine; tmtd, captan, folpet; Zineb, Propineb, sulphur; dinitrocrotonate, dichlone, chloroneb; binapacryl, a nitre phthalein isopropyl ester, dodine; the Delan, fentin hydroxide, fentinacetate; tecnazene, pcnb, botran; the compound of cupric such as copper oxychloride, copper sulphate and purplish red mixture, and organomercurial compound.
For protective plant, eliminate the seed seedbed, soil base mycosis soil or leaf, general formula (I) compound can mix with soil, peat or other medium that can take root.
The suitable bactericide that can mix in the present composition comprises: Aphox, Rogor, different suction phosphorus, peace fruit, sevin, isoprocarb, XMC (XMC), Bassa (BPMC), the furans pellet, carbosulfan, ground industry farming, fenthion kills the snout moth's larva powder, phenthoate dimephenthoate cidial, chlopyrifos, isoxathion, ethoprop, nuvacron, Buprofezin, ethroproxyfen and cycloprothrin.
Plant growth regulating compound can be controlled the growth of weeds or grain ear, perhaps the growth of the unwanted plant of Selective Control (as weeds).
The plant growth regulating compound that uses with The compounds of this invention has gibberellin (as gibberellin-3, gibberellin-4 or gibberellin-7), and auxin is (as heteroauxin, indolebutyric acid, naphthoxyacetic acid or naphthyl acetic acid), and the basic element of cell division (as kinetin, diphenylurea, benzimidazole, benzyl line purine or benayl aminopurine), phenoxyacetic acid (as 2,4-drips or 2 first, 4 chlorine), substituted benzoic acid (as Triiodobenzoic acid), morphactin (as Chlorfluoroecol), maleic acid hydrazide, glyphosate, glyphosine, the pure and mild acid of long-chain fat, dikegulac, Paclobutrazol, amine fluoride, mefluidiede replaces quaternary ammonium and phosphorus compound (as the chlormequat anion, phosphorus chloride or mepiquatchloride), ethrel, carbetamide, 3, the fragrant sour methyl esters of 6-dichloro seedling, daminozide, asulam, abscisic acid, isopyrimol, the 1-(4-chlorphenyl)-4,6-dimethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid, 4-hydroxy-benzonitrile (as Brominal), the grass pyrazoles, benzoyl third-ethyl 3,6-lontrel, fenpentezol, inabenfide, triapenthenol and tecnazene.
Following Example explanation the present invention.In all examples, term " ether " refers to diethyl ether, uses dried over mgso solution, and solution under reduced pressure concentrates.Relate to being reflected in the nitrogen atmosphere of water-sensitive intermediate and carry out, dry solvent suitably before the use.Unless otherwise indicated, all fix and carry out chromatography mutually with silicagel column.Represented data, infrared and nuclear magnetic resonnance (n.m.r) data are selectively, in all cases all attempt list each absworption peak.Unless otherwise noted, 1Hn.m.r spectrum all uses CDCl 3The solution record.Use following abbreviation:
The DME=dimethoxy-ethane
THF=tetrafluoro furans
DMF=N, dinethylformamide
The n.m.r=nuclear magnetic resonnance
IR=is infrared
The S=single line
The d=two-wire
The t=triplet
The m=multiplets
The m.p.=fusing point
The GC=gas-chromatography
The TLC=thin layer chromatography
The HPLC=high performance liquid chromatography
Br=is wide
Ppm=1,000,000/
Embodiment 1
Present embodiment explanation (E)-2-(2-(3-benzyloxy phenoxy group) phenyl)-preparation method of 3-methoxy-methyl acrylate (table I compound 23).
Figure 881072702_IMG79
With 2-bromobenzene formaldehyde (100 grams, 0.54 mole), ethylene glycol (67.03 grams, 1.08 moles), the mixture heating of right-toluene sulfonic acide (0.5 gram) and toluene kept reflux temperature 6 hours.During this period, remove through azeotropic distillation and anhydrate/ethylene glycol (23 milliliters).With the mixture cooling, add ether (1 liter).This diethyl ether solution washs with saturated sodium bicarbonate solution (200 milliliters), water (3 * 150 milliliters) and saturated brine (1 * 150 milliliter), after drying, the filtration, diethyl ether solution is evaporated, obtain oily 2-(2-bromo phenyl)-1,3-dioxolanes (121.96 grams, productive rate 98.6%).
1Hn.m.r.（60MHz）δ：3.4（4H，m），6.0（1H，S），6.9-7.6（4H，m）ppm。
This raw material need not further be purified and promptly be can be used for following steps.
In potassium hydroxide pellets (35.2 grams, 0.63 mole) water-soluble (50 milliliters), add trimethoxy phenol (78 grams, 0.63 mole) and toluene (250 milliliters).With mixture heating and maintain reflux temperature, distilled (collecting 65 milliliters in water altogether) until water.Mixture is chilled to 80 ℃, adds 2-(2-bromo phenyl)-1,3-dioxolanes (120 grams, 0.524 mole), DMF(200 milliliter) and stannous chloride (0.2 gram).Mixture slowly is heated to 150～155 ℃, and toluene is removed in distillation.Mixture was kept 6 hours down at 150～155 ℃, be cooled to 25 ℃ then, add 500 ml waters.Mixture is filtered, with ether (200 milliliters) washing residue.With ether (3 * 150 milliliters) extraction filtrate, the ether extraction liquid of collection washs with 2N sodium hydroxide solution (2 * 150 milliliters), water (4 * 150 milliliters) and saturated brine (1 * 200 milliliter).After drying, the filtration,, obtain oily 2-(2-(3-methoxyl group phenoxy group) phenyl with the diethyl ether solution evaporation)-1,3-dioxolanes (124.1 grams, productive rate 87.1%).
1Hn.m.r.（60MHz）δ：3.65（3H，S），3.95（4H，d），6.12（1H，S），6.6-7.6（8H，m）ppm。
This raw material need not further be purified and promptly be can be used for following reaction.
With 2-(2-(3-methoxyl group phenoxy group) phenyl)-1,3-dioxolanes (32.7 grams, 0.12 mole) place the mixture of water (95 milliliters) and concentrated hydrochloric acid (5 milliliters), at room temperature stirred 19 hours, extract this mixture with ether (2 * 60 milliliters), the ether extraction liquid of collecting washs with saturated sodium bicarbonate aqueous solution (30 milliliters), water (3 * 30 milliliters) and saturated brine (30 milliliters).Gained solution drying, filtration also concentrate, and obtain pure basically oily 2-(3-methoxyl group phenoxy group)-benzaldehyde (A) (26.17 grams, productive rate 95.4%).This raw material need not be purified and promptly be can be used for following step.Separate the preparation analytic sample with chromatography, make elutriant with the mixture of ether and hexane, products obtained therefrom is amber oily thing.
1Hn.m.r.（90MHz）δ：3.79（3H，S），6.58-7.97（8H，m），10.49（1H，d）ppm。
IR maximum peak (film): 1691,1599Cm -1
With 2-(3-methoxyl group phenoxy group) benzaldehyde (25.0 grams, 0.109 mole), methyl methylthiomethyl sulfoxide (13.64 grams, 0.11 mole), the mixture of benzyltrimethylammonium hydroxide (8.0 milliliters, 30% methanol solution) and oxolane (THF) (150 milliliters) stirred 45 minutes under reflux temperature.The gained solution evaporation is to doing, and carries out chromatography with the mixed liquor of ether and hexane as elutriant, obtains the sulfoxide compound (B) (27.67 restrain productive rate 75.3%) of amber colloid shape.
1Hn.m.r.（60MHz）δ：2.2（3H，S），2.55（3H，S），3.65（3H，S），6.35-8.15（9H，m）ppm。
Chloroacetic chloride (20 milliliters) was added drop-wise in 15 minutes in the absolute methanol (200 milliliters), with water-bath cooling and maintain 20-25 ℃.Add sulfoxide compound (B) (27.67 grams again, 0.083 solution in methyl alcohol (40 milliliters) mole) stirred 18 hours under the room temperature, under the decompression with this methanol solution evaporate to dryness, obtain sepia jelly (22.78 gram), it is dissolved in the ether (200 milliliters).This diethyl ether solution washs with saturated sodium bicarbonate aqueous solution, filter a small amount of insoluble matter, diethyl ether solution is evaporated to dried, residue separates with chromatography, mixed liquor with ether and hexane is made elutriant, obtain the 2-(3-methoxyl group phenoxy group of viscosity oily) methyl phenylacetate (C) (15.62 grams, productive rate 69.3%).
1Hn.m.r.（60MHz）δ：3.5（3H，S），3.59（2H，S），3.63（3H，S），6.35-7.32（8H，m）ppm。
With Boron tribromide (12.89 grams, 0.051 mole) be dissolved in the carrene (50 milliliters), be cooled to 0-5 ℃, under agitation, dropping 2-(3-methoxyl group phenoxy group in one hour) carrene (80 milliliters) solution of methyl phenylacetate (7.0 grams, 0.026 mole).At 0-5 ℃ this mixture was stirred 20 minutes, then this mixture is added drop-wise in the absolute methanol (100 milliliters) that maintains 0-5 ℃.Gained solution is poured in the water (250 milliliters) that contains sodium bicarbonate (12 gram), uses ether (500 milliliters) extraction then.Organic facies water (3 * 200 milliliters) and saturated brine (150 milliliters) washing.After drying, the filtration, evaporate this diethyl ether solution, obtain the 2-(3-hydroxyphenoxy of sepia glue) methyl phenylacetate (D) (6.12 grams, productive rate 92.3%).This raw material does not need further purification promptly to can be used for following step.Make elutriant with ether and hexane mixed liquor, carry out chromatography and separate, make high-purity raw, this raw material is the golden yellow viscous oil that is exposed to rapid blackening in the air.
In addition, 2-(3-hydroxyphenoxy) methyl phenylacetate (D) also can prepare by the following method:
At 140 ℃, the stannous chloride of catalytic amount exists down, heated and stirred 2-chlorophenyl acetic acid (30 grams, 0.18 mole), the mixture of potash (48.6 grams, 0.34 mole) and 3-metoxyphenol (43.5 grams, 0.35 mole).After three hours, GC and TLC the analysis showed that initial carboxylic acid does not exist.With reactant mixture cooling (become too sticking for preventing mixture, add dry DMF(5 milliliter) at 70 ℃), pour in the water, use the concentrated hydrochloric acid acidifying.Gained mixture extracted with diethyl ether, the ether extraction liquid of collection washes with water to neutrality.With the ether extraction liquid drying, evaporation obtains 3-metoxyphenol (49%) and 2-(3-methoxyl group phenoxy group) mixture of phenylacetic acid (41%).This mixture is the flowable grease of sepia, does not need further purification promptly to can be used for next step reaction.
This sepia oil was refluxed 2 1/2 hours in the methyl alcohol that contains the concentrated sulfuric acid (2 milliliters) (70 milliliters) solution.Reactant mixture is chilled to room temperature, pour in the water, with extracted with diethyl ether (* 2), the ether extraction liquid of collecting washs with dilute sodium hydroxide aqueous solution, wash with water then to neutrality and dry, evaporate to dryness obtains tenne oily crude product 2-(3-methoxyl group phenoxy group) methyl phenylacetate (34.9 gram), (it is 86% that GC records purity).This crude product with use another batch crude product made from quadrat method (8.2 gram) altogether, carry out repeatedly short-path distillation (50-120 ℃, 4 * 10 -2Millibar), obtain oily 2-(3-methoxyl group phenoxy group) methyl phenylacetate (calculating productive rate by the 2-chlorophenyl acetic acid is 60% for 37.1 grams, purity 95%), prepare more product subsequently.
Under 110 ℃, with 2-(3-methoxyl group phenoxy group) methyl phenylacetate (97 grams, 0.36 mole) heated 8 hours with concentrated hydrobromic acid (194 milliliters) (150 milliliters) in acetate, under room temperature, place a night, and then the denseer hydrobromic acid (100 milliliters) of adding, reactant mixture is heated to 110 ℃ again, after reacting 7 hours again, all initiation material total overall reactions are fallen, reactant mixture is chilled to room temperature, pours in the salt solution, use carrene (* 2) extraction then, carrene is evaporated, get a grease.This grease heated 2 hours with the methyl alcohol (400 milliliters) and the concentrated sulfuric acid (2 milliliters) at 70 ℃.Reactant mixture is chilled to room temperature, pours in the salt solution, with carrene (* 2) extraction.The extract of collecting washes (to neutral) with water, and drying, filtration, evaporate to dryness obtain a kind of brown oil (92.8 gram).Short-path distillation portion of product (72.8 gram) obtains the 2-(3-hydroxyphenoxy) to calculate productive rate be 57% to methyl phenylacetate (D) (41.4 grams are from 2-(3-methoxyl group phenoxy group) methyl phenylacetate), product is golden yellow slurries.
1Hn.m.r.（60MHz）δ：3.57（3H，S），3.63（2H，S），5.82（1H，S），6.4-7.35（8H，m）ppm。
IR maximum peak (film): 3408,1713Cm -1
Toward sodium hydride (0.558 gram, 0.023 DMF(20 milliliter mole)) drip the 2-(3-hydroxyphenoxy in the suspension) methyl phenylacetate (D) (2.0 grams, 0.0077 solution and methyl formate (10 grams DMF(10 milliliter mole)), 0.167 mole), stir after 45 minutes, add entry (100 milliliters), this mixture extracts with ether (50 milliliters), water to PH3-4, is used extracted with diethyl ether (2 * 40 milliliters) with hcl acidifying.Ether extraction liquid water of collecting (3 * 30 milliliters) and saturated brine (1 * 30 milliliter) washing, dry then.Ether is evaporated, and residue is dissolved in the DMF(20 milliliter) in, add Anhydrous potassium carbonate (0.64 gram, 0.0046 mole) and dimethyl suflfate (0.55 gram, 0.0044 mole).Mixture stirred under room temperature one hour, added entry (100 milliliters), with ether (2 * 40 milliliters) extraction.Ether extraction liquid water of collecting (3 * 20 milliliters) and saturated brine (20 milliliters) washing, dry, filter, be evaporated to dried, separate with chromatography then, mixed liquor with ether and hexane is made elutriant, obtain amber jelly (E)-2-(2-(3-hydroxyphenoxy) phenyl)-3-methoxy-methyl acrylate (E), this compound obtains a kind of white solid (0.7 gram with hexane and dichloromethane mixture development, from the 2-(3-hydroxyphenoxy) to calculate productive rate be 30% to methyl phenylacetate (D)), fusing point is 115-116 ℃.
In addition, (E)-2-(2-(3-hydroxyphenoxy) phenyl)-3-methoxy-methyl acrylate (E) also can be by the preparation of following method:
In 45 minutes, stir down, with the 2-(3-hydroxyphenoxy) methyl phenylacetate (D) (12 grams, 0.0465 mole) and methyl formate (55.8 grams, 0.93 dry DMF(35 milliliter mole)) solution is added to sodium hydride (6.696 grams, 50% dispersed oil, is crossed with 40-60 milliliter petroleum ether in advance by 0.1395 mole) dry DMF(65 milliliter) in the suspension.Reactant mixture stirred under room temperature 2 1/2 hours, poured in the water (200 milliliters), was acidified to PH3 with concentrated hydrochloric acid, with ether (2 * 200 milliliters) extraction.The organic extract of collecting washs with salt solution (2 * 200 milliliters), and drying is filtered, and evaporate to dryness obtains a kind of yellow oil (12.5 grams, 0.0433 mole).Should oil (12.5 grams, 0.0433 mole) be dissolved in dry DMF(100 milliliter) in, add potash (5.98 grams, 0.0433 mole).Stir after 10 minutes, add the DMF(10 milliliter of dimethyl suflfate (5.19 grams, 0.042 mole)) solution (once adding).The mixture that obtains at room temperature stirs a night, pours in the water (200 milliliters), with ether (2 * 200 milliliters) extraction.The ether extraction liquid of collecting washs with salt solution (3 * 200 milliliters), and drying is filtered, and evaporate to dryness obtains viscoloid.Crystallization obtains (E)-2-(2-(3-hydroxyphenoxy) phenyl in carrene-hexane)-3-methoxy-methyl acrylate (E) (9.54 grams, 73%), fusing point 117-118 ℃.
1Hn.m.r.（90MHz）δ：3.58（3H，S），3.75（3H，S），5.38（1H，S），6.39-7.33（8H，m），7.4（1H，S）ppm。
IR maximum peak (atoleine): 3295,1672,1630Cm -1
With (E)-2-(2-(3-hydroxyphenoxy) phenyl)-3-methoxy-methyl acrylate (1.0 grams, 0.0033 mole), bromomethyl benzene (0.57 gram, 0.0033 mole), potash (0.8 gram, 0.0053 mole) and dry DMF(15 milliliter) mixture at room temperature stirred 3 hours, add entry (50 milliliters), extract with ether (2 * 30 milliliters).Organic extract water (2 * 20 milliliters) washing of collecting is after drying, the filtration, with the diethyl ether solution evaporate to dryness, make elutriant with the mixture of ether and hexane then, carry out chromatography and separate, the desire that obtains colourless glue prepares compound (F) (1.11 grams, productive rate 85%).
1Hn.m.r（90MHz）δ：3.55（3H，S），3.7（3H，S），4.97（2H，S），6.5-7.32（13H，m），7.44（1H，S）ppm。
IR maximum peak (film): 1710,1638Cm -1
Embodiment 2
The preparation method of present embodiment explanation (E)-3-methoxyl group-2-(2-(3-phenylsulfonyloxy phenoxy group)-phenylacrylic acid methyl esters (table I compound 51).
With (E)-2-(2-(3-hydroxyphenoxy)-phenyl)-3-methoxy-methyl acrylate (0.5 gram, 0.00166 mole, method preparation by embodiment 1), benzene sulfonyl chloride (0.36 gram, 0.002 mole) and the mixture of pyridine (10 milliliters) 60-70 ℃ of stirring 3 hours down, mixture is chilled to 25 ℃, adds water (60 milliliters), extract this mixture with ether (2 * 30 milliliters).The ether extraction liquid water of collecting (20 milliliters), watery hydrochloric acid (20 milliliters), water (93 * 200 milliliters) and saturated brine (20 milliliters) washing.The diethyl ether solution drying is filtered, and after concentrating, makes elutriant with chloroform and hexane mixed liquor, carries out chromatography and separates, and the desire that obtains colourless glue prepares compound (0.21 gram, productive rate 28.7%).
1Hn.m.r.（90MHz）δ：3.56（3H，S），3.75（3H，S），6.52-7.96（13H，m），7.40（1H，S）ppm。
Embodiment 3
Present embodiment explanation (E)-3-methoxyl group-2-(2-(3-(4-nitro-phenoxy) phenoxy group) phenyl)-preparation method of methyl acrylate (compound 133 in the table I).
With (E)-2-(2-(3-hydroxyphenoxy) phenyl)-3-methoxy-methyl acrylate (1.2 grams, 0.004 mole, press the method preparation of embodiment 1), 4-nitro fluorobenzene (0.68 gram, 0.008 mole), potash (1.1 gram, 0.008 mole) and DMF(15 milliliter) mixture at room temperature stirred 16 hours, pour into then in the water (80 milliliters), with ether (2 * 30 milliliters) extraction.Saturated brine (25 milliliters) washing is used in organic extract water (3 * 25 milliliters) washing of collecting then.Carry out drying then, filter, concentrate, make elutriant with the mixture of chloroform and hexane, carry out chromatography and separate, the desire that obtains amber glue prepares compound (0.93 gram, productive rate 55.2%).
1H NMR（90MHz）δ：3.55（3H，S），3.72（3H，S），6.67-8.41（12H，m），7.44（1H，S）ppm。
Embodiment 4
Present embodiment explanation (E)-2-(2-(3-(4-fluorinated phenoxy) phenoxy group) phenyl)-preparation method of 3-methoxy-methyl acrylate (table I compound 124).
With (E)-2-(2-(3-hydroxyphenoxy) phenyl)-3-methoxy-methyl acrylate (1.0 grams, 0.0033 mole, method preparation by embodiment 1), two (4-fluoro phenyl) IBr (2.63 grams, 0.0069 mole), triethylamine (0.5 milliliter), the copper powder (0.5 gram) and the mixture of absolute methanol (15 milliliters) added hot reflux 6 hours, add two (4-fluoro phenyl) IBrs (1 gram, 0.0069 mole) again, continued stirring and refluxing 3 hours.Cooling after the filtration, adds water (80 milliliters) in filtrate, extract this mixture with ether (2 * 30 milliliters).Ethereal extract water of collecting (3 * 15 milliliters) and saturated brine (15 milliliters) washing, drying is filtered, and this diethyl ether solution is concentrated, and the desire that obtains amber glue prepares compound (0.16 gram, productive rate 12.3%).
1Hn.m.r.（60MHz）δ：3.42（3H，S），3.51（3H，S），6.35-7.30（12H，m），7.35（1H，S）ppm。
IR maximum peak (film): 1710,1641Cm -1
Embodiment 5
Present embodiment explanation (E)-2-(2-(3-benzoyloxy phenoxy group) phenyl)-preparation method of 3-methoxy-methyl acrylate (table I compound 49).
With (E)-2-(2-(3-hydroxyphenoxy) phenyl)-3-methoxy-methyl acrylate (0.5 gram, 0.00166 mole, press the method preparation of embodiment 1), chlorobenzoyl chloride (0.26 gram, 0.00185 mole), potash (0.23 gram, 0.00166 mole) and DMF(10 milliliter) mixture at room temperature stirred 1 1/2 hours.Add chlorobenzoyl chloride (0.26 gram, 0.00166 mole) and potash (0.23 gram, 0.00166 mole) again, under room temperature, mixture was stirred 16 hours.Add entry (80 milliliters), mixture extracts with ether (2 * 40 milliliters).Ether extraction liquid water of collecting (3 * 20 milliliters) and saturated brine (20ml) washing, dry then, filter, concentrate, carry out chromatography with the mixture of ether and hexane as elutriant and separate, obtain a kind of white solid, in aqueous methanol the recrystallization obtain pure desire prepare compound (0.32 the gram, productive rate 47.7%), is white solid, fusing point 94-95 ℃.
1Hn.m.r.（90MHz）δ：3.62（3H，S），3.74（3H，S），6.76-8.38（13H，m），7.46（1H，S）ppm。
IR maximum peak (atoleine): 1741,1698,1627Cm -1
Embodiment 6
The preparation method of present embodiment explanation (E, E)-2-(2-(3-(4-chlorobenzene azo group)-4-hydroxyphenoxy) phenyl)-3-methoxy-methyl acrylate (table I compound 282).
1M hydrochloric acid (2.5ml) is added in the trichloroaniline hydrochloric acid (the 0.25M aqueous solution of 6.64ml), and mixture is cooled to below 10 ℃, drips natrium nitrosum (the 0.5M aqueous solution of 3.32ml), and this mixture was being stirred 10 minutes below 10 ℃.The 3-chlorobenzene diazonium chloride solution that obtains under agitation is added drop-wise to (E)-2-(2-(4-hydroxyphenoxy) phenyl)-3-methoxy-methyl acrylate (0.5 gram, 0.00166mol, with the preparation of the corresponding 3-hydroxy compounds of embodiment 1 described preparation similar methods), in the mixture of sodium hydroxide (the 0.1M aqueous solution of 16.6ml) and acetone (30ml).Meanwhile, add sodium hydrate aqueous solution again, make pH value remain on 8-10, simultaneous temperature maintains below 10 ℃, stir after 20 minutes, mixture is with ether (2 * 40ml) extractions, the ethereal extract water of collection (3 * 15ml) and saturated brine (15ml) washing, drying then, filter, concentrate, carry out chromatography with the mixture of ether and hexane as elutriant and separate, obtain orange solids.In the mixture of hexane and carrene, be recrystallized, obtain pure desire and prepare compound (99.3mg, productive rate 13.6%), fusing point 143-144 ℃.
Embodiment 7
Present embodiment explanation (E)-2-(2-(3-(3-methoxyl group phenoxy group) phenoxy group) phenyl)-preparation method of 3-methoxy-methyl acrylate (table I compound 129).
Under agitation, disposable adding resorcinol in methyl alcohol (10ml) solution of sodium (0.61 gram) (4.34 gram), at room temperature stirred 1/2 hour, excessive methanol is removed in decompression then, in the orange oil that obtains, add pyridine (6.6ml) again, 3-bromoanisole (14.74 gram) and stannous chloride (192 milligrams).This mixture stirred 66 hours at 125 ℃, cooling, then reactant mixture is poured in the watery hydrochloric acid, use extracted with diethyl ether, ether extraction liquid extracts with dilute sodium hydroxide aqueous solution again, and these water extracts are with the watery hydrochloric acid acidifying and use extracted with diethyl ether, and these ether extraction liquids are water and salt water washing successively, dry then and concentrated, obtain 3.72 gram reddish oil.Bubbling distills this oil (170 ℃ of temperature of reactor 0.05mmHg), obtain the faint yellow oily thing 3-(3-methoxyl group phenoxy group of thickness) phenol (1.71 gram).
1Hn.m.r.δ：3.78（3H，S），4.93（1H，S）ppm。
Under agitation, disposable adding 3-(3-methoxyl group phenoxy group in methyl alcohol (4ml) solution of sodium (0.18 gram)) phenol (1.70 gram), at room temperature stirred this mixture 1/2 hour, excessive methanol is removed in decompression.In the orange oil that obtains, add neighbour-bromobenzene acetate (0.85 gram) and stannous chloride (40 milligrams), at 130 ℃ reactant mixture was stirred 1 hour, add neighbour-bromobenzene acetate (0.4 gram) and caustic alcohol (0.13 gram) again, mixture continues to stir 3 hours at 130 ℃, place cooling, use the watery hydrochloric acid acidifying then, use extracted with diethyl ether.Ether extraction liquid is water and salt water washing successively, and is dry then, concentrates, and obtains containing 2-(3-(3-methoxyl group phenoxy group) phenoxy group) reddish oil (3.12 gram) of phenylacetic acid.Add methyl alcohol (40ml) and 3 concentrated sulfuric acids in the thick product of this acid (3.12 gram), this reactant mixture was stirred 1 hour at 90 ℃, placement is cooled off, and pours in the water and uses extracted with diethyl ether.Ether extraction liquid is used dilute sodium hydroxide aqueous solution successively, water and salt water washing, dry then, concentrate, obtain 1.33 the gram yellow oils, bubbling distill this oil (160 ℃ of temperature of reactor, 0.07mmHg), obtain 2-(3-(3-methoxyl group phenoxy group) phenoxy group) to calculate productive rate be 36% to methyl phenylacetate (1.03 gram, from 3-(3-methoxyl group phenoxy group) phenol).
1Hn.m.r.δ：3.62（3H，S），3.68（2H，S），3.78（3H，S）ppm。
With 2-(3-(3-methoxyl group phenoxy group) phenoxy group) methyl phenylacetate (1.00 gram) and methyl formate (3.34ml) be dissolved in DMF(1ml) mixed liquor, in 10 minutes, under stirring, be added drop-wise to the DMF(10ml of the sodium hydride (0.13 restrains) that water is chilled to (effervesce) below 10 ℃) in the suspension.After adding, reactant at room temperature stirred 2 hours, poured in the water, used the watery hydrochloric acid acidifying, used extracted with diethyl ether then, and extract washes with water, and drying concentrates, and obtained yellow oil (1.09 gram).Stirring down successively the DMF(20ml that potash (0.76 gram) and dimethyl suflfate (0.33 restrains) is joined this yellow oil) in the solution, reactant stirred under room temperature 2 1/2 hours, poured in the water, used extracted with diethyl ether then.Extract washes with water, and drying concentrates, make elutriant with 1: 1 ether and gasoline mixed liquor, carry out chromatography and separate, the desire that obtains colourless thickness oily prepares compound (0.61 gram is from 2-(3-(3-methoxyl group phenoxy group) phenoxy group) methyl phenylacetate, and to calculate productive rate be 55%).
1Hn.m.r.δ：3.60（3H，S），3.75（3H，S），3.78（3H，S），6.55-6.72（5H，m），6.97（1H，d），7.10-7.30（6H，m），7.48（1H，S）ppm。
IR maximum peak (atoleine): 1713,1638Cm -1
Embodiment 8
Present embodiment explanation (E)-3-methoxyl group-2-(2-(3-(phenoxymethyl) phenoxy group) phenyl) preparation method of methyl acrylate (table I compound 21).
(E)-and 3-methoxyl group-2-(2-(3-methylphenoxy) phenyl) methyl acrylate (0.50 gram, press embodiment 1 described method by 3-methylphenol and 2-bromobenzene prepared formaldehyde) and N-bromo-succinimide (0.30 gram), in containing the carbon tetrachloride of micro-azodiisobutyronitrile (25ml), refluxed 4.5 hours, added once micro-AIBN every 1.5 hours.Reaction is monitored by GC.At room temperature place a night, in reactant, add micro-AIBN again, continue to reflux, the analysis showed that almost all disappearances (1 hour) of initiation material up to GC.Reactant filters through C salt (diatomite), washing, and evaporation obtains faint yellow gluey thing (0.69 gram).GC and NMR the analysis showed that this jelly is made of following composition: (E)-and 2-(2-(3-bromomethyl phenoxy group) phenyl)-3-methoxy-methyl acrylate (80%), corresponding dibromo methyl compound (11%) and unreacted acrylate initiation material (8%).
1Hn.m.r. Main Ingredients and Appearance data, δ: 3.61(3H, S), 3.77(3H, S), 4.42(2H, S), 6.90-7.40(8H, m), 7.48(1H, S) ppm.
This raw material does not need further purification to use.
The thick product of part material (0.42 gram, purity 80%) and phenol (0.105 gram) and potash (0.077 gram) are at DMF(20ml) in stirring, be heated to 60 ℃, reacted 1 hour.Place a night under the room temperature, be heated to 60 ℃ of reactions 1 hour again, cooling is poured in the water, uses ethyl acetate extraction.Organic facies washes with water, drying, and evaporation obtains faint yellow oily thing (0.42 gram).Purify with high performance liquid chromatography, with 3: 1 gasoline and the elution of ethyl acetate mixed liquor, the desire that obtains colourless glue prepares compound (0.13 gram), wherein contains 20% impurity (E)-2-(2-(3-xylylene bromide oxygen base) phenyl)-the 3-methoxy-methyl acrylate.
1Hn.m.r (desire prepares the compound data) δ: 3.58(3H, S), 3.70(3H, S), 4.98(2H, S), 6.88-7.36(13H, m), 7.46(1H, S) ppm.
Embodiment 9
Present embodiment explanation (E)-2-(2-(2-acetyl group-5-phenoxy group phenoxy group) phenyl)-3-methoxy-methyl acrylate and (E)-2-(2-(4-acetyl group-3-phenoxy group phenoxy group) phenyl)-preparation method of 3-methoxy-methyl acrylate (table I compound 366 and compound 365).
Preparation 2-(3-methoxyl group phenoxy group according to description among the embodiment 1) step of methyl phenylacetate prepares 2-(3-phenoxy group phenoxy group by 3-phenoxy phenyl and 2-bromobenzaldehyde) methyl phenylacetate.This compound can be by preparation (E)-2-(2-(3-hydroxyphenoxy) phenyl described in the embodiment 1)-step of 3-methoxy-methyl acrylate, with sodium hydride and methyl formate reaction, then with potash and dimethyl suflfate reaction, just the sodium hydride consumption is equivalent to the twice of embodiment 1 consumption, is converted into compound (E)-3-methoxyl group-2-(2-(3-phenoxy group phenoxy group) phenyl) methyl acrylate ( 1Hn.m.r.(250MHz), 3.61(3H, S), 3.78(3H, S), 6.68-7.35(13H, m), 7.48(1H, S) ppm).
Aluminium chloride (0.512 gram with grind into powder, 3.84 mM), under agitation, 0～5 ℃, adding (E)-3-methoxyl group-2-(2-(3-phenoxy group phenoxy group) phenyl) in the dry methylene chloride solution of methyl acrylate (0.722 gram, 1.92 mMs).Then, the dry methylene chloride solution (3ml) of dripping acetyl chloride in 10 minutes (0.151 gram, 1.92 mMs) stirs a night with the gained mixture, makes its temperature recovery to room temperature.Reactant mixture is with ether (125ml) dilution, and with 2N hydrochloric acid (* 2), the washing of 10% aqueous sodium carbonate washes with water at last.Except that after desolvating, the gained residue separates with the flash chromatography method purifies, mixture with ether and gasoline is made elutriant, and two kinds of desires that obtain colourless glue prepare about 3: 1 mixture of compound (0.424 gram), (characteristic of independent a kind of compound is not determined).Part jelly (0.400 gram) separates with high performance liquid chromatography, adopt silicagel column, hexane with 70: 25: 5: carrene: the methyl tert butyl ether mixture is made elutriant, obtain (I) regional isomer A(RegioisomerA) (0.179 gram), at first wash out, be white crystalline solid, fusing point 90-92 ℃ is the Main Ingredients and Appearance of mixture.
1Hn.m.r.（250MHz）δ：2.52（3H，S），3.56（3H，S），3.72（3H，S），6.48（1H，d），6.64（1H，q），6.9-7.4（9H，m），7.43（1H，S），7.84（1H，d）ppm。
(II) regional isomer B(RegioisomerB) (0.061 gram contains 5% regional isomer A as calculated), second washes out, and is composition less in the mixture, is white crystalline solid, fusing point 82-85 ℃.
1Hn.m.r.（250MHz）δ：2.51（3H，S），3.60（3H，S），3.75（3H，S），6.45（1H，d），6.59（1H，q），6.9-7.4（9H，m），7.48（1H，S），7.82（1H，d）ppm。
Embodiment 10
Present embodiment explanation (E)-3-methoxyl group-2-(2-(3-pyrimidine-2-oxygen phenoxyl) phenyl) preparation method of methyl acrylate (table II compound 22).
With (E)-2-(2-(3-hydroxyphenoxy) phenyl)-3-methoxy-methyl acrylate (0.5 gram, press embodiment 1 described method preparation), potash (0.46 gram), the mixture of 2-chlorine pyrimidine (0.23 gram) and stannous chloride (0.01 restrains) is at DMF(15ml) in added hot reflux 4 hours.After the cooling, pour in the water this mixture and filtration.Filtrate is used extracted with diethyl ether, and the ether extraction liquid of collection is water and salt water washing successively, and drying concentrates, and carries out chromatography with the mixture of ether and hexane as elutriant and separates, obtains the compound (0.26 restrains productive rate 41%) that gluey desire prepares.
The IR(film): 1707,1633Cm -1
1Hn.m.r.（90MHz）δ：3.54（3H，S），3.68（3H，S），6.74-7.34（9H，m），7.38（1H，S），8.28（2H，d）ppm。
Embodiment 11
Present embodiment explanation (E)-3-methoxyl group-2-(2-(3-phenoxy group thiophenyl) phenyl) preparation method of methyl acrylate (table III compound 446):
Figure 881072702_IMG80
According to the method described in the Chemistry Literature prepare 2-mercaptophenyl-acetate (see D.Papa etc., J.Org.Chem., 1949,24,723, R.H.Glauert and F.G.Mann, J.Chem.Soe., 1952,2127 and wherein list of references).Under agitation, 2-sulfydryl phenylacetic acid (1.68 gram) is joined in methyl alcohol (10ml) solution of sodium hydroxide (0.8 gram), (with reference to D.C.Atkinson etc., J.Med.Chem., 1983,26,1361).The orange solution that obtains was at room temperature stirred 90 minutes, and concentrating under reduced pressure through removing last remaining methyl alcohol with the methylbenzene azeotropic distillation, obtains yellow solid then.DMF(20ml in this yellow solid) adds stannous chloride (0.2 gram) and 3-phenoxy group bromobenzene (2.49 grams in the agitating solution successively, press J.P.Schaefer etc., Org.Synth., Coll.Vol.5, method described in 142 is by the preparation of 3-phenoxy phenyl and dibrominated triphenylphosphine) DMF(10ml) solution.The mixture that obtains, is poured reactant in the sodium hydrate aqueous solution into 125 ℃ of heating 2 hours 95 ℃ of heating 1 3/4 hours, uses ether (* 3) washing then, and aqueous solution concentrated hydrochloric acid acidifying is with extracted with diethyl ether (* 3).These extracts wash with water, and drying concentrates, and is mainly contained 2-(3-phenoxy group thiophenyl) violet oil (2.2 gram) of phenylacetic acid.Methyl alcohol (20ml) solution of this oil is added in the acid methyl alcohol (handle methyl alcohol (30ml) carefully and make with chloroacetic chloride (3.5ml)), the mixture that obtains at room temperature stirred 90 minutes.This reactant is concentrated, residue distributes between ether and sodium bicarbonate aqueous solution two-phase, organic facies is isolated, use the washing of sodium hydrate aqueous solution (* 2) and water (* 3) successively, dry then, concentrate, obtain the 2-(3-phenoxy group thiophenyl of purple oily) methyl phenylacetate crude product (2.06 gram).
IR maximum peak (film): 1740Cm -1, GC measures purity 94%.
Thick product 2-(3-phenoxy group thiophenyl) methyl phenylacetate, described by embodiment 7 with 2-(3-(3-methoxyl group phenoxy group) phenoxy group) the phenylacetic acid methyl esters is converted into (E)-2-(2-(3-(3-methoxyl group phenoxy group) phenoxy group) phenyl)-two-step reaction of 3-methoxy-methyl acrylate, be converted into the compound of desire preparation, productive rate is 53%, promptly, carry out the O monomethylization with dimethyl suflfate and potash then with methyl formate and sodium hydride reaction.Product is orange jelly, and it is 98% that GC measures purity, leaves standstill crystallization.Fusing point 48-51.5 ℃.
IR maximum peak (film): 1710 and 1632Cm -1
1Hn.m.r.（270MHz）δ：3.62（3H，S），3.73（3H，S），6.78（1H，dd），6.88-7.00（4H，m），7.05-7.36（7H，m），7.42（1H，d），7.48（1H，S）ppm。
Embodiment 12
Present embodiment explanation (E)-2-(2-(3-pyrimidine-2-oxygen base thiophenyl) phenyl)-preparation method of 3-methoxy-methyl acrylate (table IV compound 22).
The sodium salt of 3-methoxyl group thiophenol (is handled 3-methoxyl group thiophenol (2.8 gram) with sodium hydroxide (0.8 gram) in methyl alcohol (20ml), be evaporated to then and do and obtain), the mixed liquor of 2-bromobenzene acetate (4.3 gram) and stannous chloride (0.4 restrains) is at dry DMF(25ml) in add one night of hot reflux.With the reactant cooling, pour into and also use the watery hydrochloric acid acidifying in the water, with ether (* 3) extraction, diluted sodium hydroxide solution (* 3) extraction of the ether extraction liquid of collection.The sodium hydrate aqueous solution extract watery hydrochloric acid acidifying of collecting extracts with ether (* 3) again.With ether extraction liquid water (* 3) washing of these collections, dry and evaporation obtains orange oil (3.5 grams, it is 96.8% that GC records purity).Methanol solution with acidity is at room temperature handled a night with this oil.Through after the general processing, obtain 2-(3-methoxybenzene sulfenyl) methyl phenylacetate (2.9 grams, it is 91% that GC records purity) yellow liquid, product does not need further purification promptly to be used for next step reaction.
1Hn.m.r.δ：3.64（3H，S），3.74（3H，S），3.86（2H，S）ppm。
IR maximum peak (film): 1739Cm -1
With 2-(3-methoxybenzene sulfenyl) methyl phenylacetate (0.86 gram) and pyridine hydrochloride (2.08 grams, excessive) in 200 ℃ of heating together, after 3 hours, cool off reactant in nitrogen atmosphere, and it is distributed in watery hydrochloric acid and ethyl acetate.Acid water is further used ethyl acetate (* 2) extraction, and the organic facies of collection extracts with dilute sodium hydroxide (* 3), and ethyl acetate (* 3) extraction is used in the alkaline extraction liquid concentrated hydrochloric acid acidifying of collection then.Collect these organic extracts, merge, wash (* 3) with water, drying, evaporation obtains pale solid (0.64 gram), handle this pale solid with the methanol solution of hydrochloric acid, after general post processing, obtain 2-(3-hydroxy benzenes sulfenyl) methyl phenylacetate (0.44 gram) reddish oil (it is 90.5% that GC measures purity), product need not be further purified and promptly be used for next step reaction.
The IR maximum peak: 3384,1738Cm -1
With 2-(3-hydroxy benzenes sulfenyl) the thick product of methyl phenylacetate (0.44 gram) and methyl formate (1.92ml) be at dry DMF(2ml) in solution, at 0-5 ℃, be added drop-wise to sodium hydride (0.21 gram under stirring, 55% oily dispersion liquid is crossed with petroleum ether in advance) dry DMF(3ml) suspension in.After 15 minutes, temperature is risen to room temperature, after 2 1/2 hours, reactant is poured in the water, use the concentrated hydrochloric acid acidifying, use ether (* 3) extraction then.The ether extraction liquid of collecting washes (* 3) with water, drying, evaporation, obtain red jelly (0.49 gram), should the redness jelly be dissolved in DMF(5ml), be chilled to 0 ℃, add potash (0.132 gram), drip the DMF solution of dimethyl suflfate (0.111 gram) then.After stirring 4 1/2 hours, reactant is poured in the water, with extracted with diethyl ether (* 3).The ether extraction liquid of collecting washes (* 3) with water, drying, evaporation obtains 2-(2-(3-hydroxy benzenes sulfenyl) phenyl)-the red jelly of 3-methoxy-methyl acrylate (0.45 gram).
The IR maximum peak: 3240,1709,1665Cm -1; M +316
1Hn.m.r.δ：3.65（3H，S），3.76（3H，S），7.47（1H，S）ppm。
Dry DMF(10ml with 2-chlorine pyrimidine (0.45 gram) and potash (0.17 gram)) solution in nitrogen atmosphere, 80-90 ℃, is handled (E)-2-(2-(3-hydroxy benzenes sulfenyl) phenyl)-the thick product of 3-methoxy-methyl acrylate (0.4 gram).After 4 1/2 hours, GC the analysis showed that and is completed into single product.The reactant mixture cooling is poured in the water, uses extracted with diethyl ether (* 4) then, and the yellow ether extraction liquid of collection washes (* 2) with water, drying, and evaporation obtains orange jelly (0.39 gram).Make elutriant with ether, carry out chromatography and separate, obtain desire and prepare the orange thickness glue of compound (0.34 gram).
The IR maximum peak: 1706,1632Cm -1
1Hn.m.r.δ：3.64（3H，S），3.75（3H，S），6.97-7.06（3H，m），7.08-7.12（1H，d），7.25-7.35（4H，m），7.46-7.48（1H，d），7.49（1H，S），8.53-8.56（2H，d）ppm。
Embodiment 13
Present embodiment explanation (E)-2-(2-(3-thiophenyl phenoxy group) phenyl)-preparation method's (table I compound 1) of 3-methoxy-methyl acrylate.
With 3-hydroxy diphenyl thioether (2.02 grams, 0.01 mole), (E)-the 2-(2-bromophenyl)-3-methoxy-methyl acrylate (1.35 grams, 0.005 mole, press and the similar transformationreation of embodiment 7 described two-step reactions, with neighbour-bromo-acid methyl esters, methyl formate and sodium hydride, then with potash and dimethyl suflfate preparation), the stannous chloride of Anhydrous potassium carbonate (0.69 gram, 0.005 mole) and catalytic amount mixes, be heated to 175 ℃, after 10 hours, mixture is chilled to room temperature, is dissolved in DMF(50ml), the solution that obtains is poured in the water (100ml), with the ether (emulsion that 2 * 100ml) extractions obtain.The ether extraction liquid of collecting successively water (2 * 100ml), the 2M sodium hydroxide solution (2 * 100ml) and water (2 * 100ml) wash.With this diethyl ether solution drying, to filter, decompression is evaporated to dried down, carries out chromatography with hexane and chloroform give elutriant and separates, and the desire that obtains the thickness oily prepares compound (0.83 restrains).
1Hn.m.r.（60MHz）δ：3.52（3H，S），3.64（3H，S），6.5-7.3（13H，m），7.42（1H，S）ppm。
Embodiment 14
Present embodiment explanation (E)-2-(2-(3-thiophenyl phenoxy group) phenyl)-and 3-methoxy-methyl acrylate-S, the preparation method of S-dioxide (table I compound 3).
3-hydroxy diphenyl sulfone (3.66 grams, 0.0156 mole), (E)-the 2-(2-bromophenyl)-3-methoxy-methyl acrylate (1.5 grams, 0.0055 mole, press the described methods preparation of embodiment 13) and Anhydrous potassium carbonate (1.1 grams, 0.0079 mole) mix with bronze with the stannous chloride of catalytic amount.Mixture heated ten hours in 170 ℃ in nitrogen atmosphere.This melt is dissolved in DMF(50ml after being cooled to room temperature) in, gained solution removes by filter mineral salt with ether (100ml) dilution with solution.This solution is water (100ml) successively, and the 2M sodium hydroxide solution (2 * 100ml), water (100ml) and saturated brine (100ml) washing.The diethyl ether solution drying is filtered, and is evaporated to driedly under the reduced pressure, and with hexane and chloroform give elutriant, chromatography is separated residue, obtains desire and prepares compound (0.66 gram).
1Hn.m.r.（60MHz）δ：3.46（3H，S），3.57（3H，S），6.6-8.0（14H，m）ppm。
Embodiment 15
Present embodiment explanation (E)-2-(2-(3-anilino-phenoxy group) phenyl)-preparation method's (table I compound 4) of 3-methoxy-methyl acrylate.
3-hydroxy diphenylamine (1.365 grams, 0.0074 mole), (E)-the 2-(2-bromophenyl)-3-methoxy-methyl acrylate (1 gram, 0.0037 mole, press the described methods preparation of embodiment 13) and Anhydrous potassium carbonate (0.517 gram, 0.0037 mole) mix with bronze with the stannous chloride of catalytic amount.170 ℃ of heating nine hours, cooling was dissolved in DMF(20ml then with mixture) in.This solution is distributed between ether and the water.(2 * 100ml) wash the ether layer water, use (2 * 100ml) washings of 1M sodium hydroxide solution then.This diethyl ether solution drying is filtered, and decompression is evaporated to dried down, makes elutriant with hexane and carrene, and remaining jelly is separated purification with chromatography, obtains desire and prepares compound (0.40 restrains).
1Hn.m.r.（60MHz）δ：3.57（3H，S），3.67（3H，S），5.75（1H，brs），6.3-7.4（13H，m），7.44（1H，S）ppm。
Embodiment 16
Present embodiment explanation (E)-2-(2-(3-N-methylaniline phenoxyl) phenyl)-preparation method's (table I compound 5) of 3-methoxy-methyl acrylate.
(2 * 50ml) with (300 milligrams of sodium hydrides with hexane, 80% oily dispersion liquid, 0.01 the oil wash mole) goes, this hydride is suspended in dry DMF(10ml) in, in this suspension, add (E)-2-(2-(3-anilino-phenoxy group) phenyl)-(290 milligrams of 3-methoxy-methyl acrylates, press the described methods preparation of embodiment 15) dry DMF(10ml) solution, the speed of adding should be able to be kept stable effervesce.After effervesce stops, stirring again 15 minutes, in 5 minutes, be added dropwise to iodomethane (2ml, excessive greatly) then.Continue to stir 30 minutes, water (50ml) dilutes this suspension carefully then.(2 * 50ml), (2 * 50ml), these ether extraction liquids filter, and are evaporated to driedly under the decompression, and the desire that obtains the thickness oily prepares compound (211 milligrams) through washing by drying with extracted with diethyl ether for aqueous emulsion.
1H NMR（60MHz）δ：3.20（3H，S），3.54（3H，S），3.65（3H，S），6.3-7.4（13H，m），
7.44（1H，S）ppm。
Embodiment 17
Present embodiment explanation (E)-3-methoxyl group-2-(2-(3-(Alpha-hydroxy benzyl) phenoxy group) preparation method's (table I compound 380) of methyl acrylate phenyl).
3-salicylic alcohol (31.0 gram) is pulverized last, and with potash (34.6 gram), 2-bromobenzene acetate (26.9 gram) and stannous chloride (a full strockle) mix in nitrogen atmosphere.Mixture is heated to 140 ℃, the powerful stirring 3 1/2 hours.Then with DMF(60ml) be added in the fused mass of stirring, with this solution cooling, pour in the water, use the watery hydrochloric acid acidifying, the water extracted with diethyl ether, ether extraction liquid washes with water, dry, evaporate, obtain the 2-(3-hydroxy methyl phenyloxy of brown oily) phenylacetic acid (42.03 gram), product need not purified and can be used.
The crude product of above-mentioned acid (41.0 gram) refluxed 3.5 hours in the methyl alcohol that contains the concentrated sulfuric acid (2.5ml) (600ml).Behind the methyl alcohol evaporate to dryness, residue is dissolved in the ethyl acetate, with the dilute sodium hydroxide aqueous solution washing, wash with water then, and drying, evaporation obtains brown oil (26.31 gram).Get 1.31 grams and purify (elutriant ethyl acetate: hexane is 1: 1), obtain the pure 2-(3-hydroxy methyl phenyloxy of faint yellow oily with HPLC) methyl phenylacetate.
1Hn.m.r.（400MHz）δ：2.12（1H，S），3.60（3H，S），3.69（3H，S），4.62（2H，S），6.95（1H，S），6.85-6.90（2H，t），7.04-7.14（2H，m），7.21-7.32（3H，m）ppm。
IR maximum peak (film): 3450,1742Cm -1
At 5 ℃, in 30 minutes with the 2-(3-hydroxy methyl phenyloxy) the thick product of phenylacetic acid methyl esters (25.0 gram) and methyl formate (56ml) be at dry DMF(50ml) and in mixed liquor be added drop-wise to sodium hydride (7.35 restrain, 60% oily dispersion liquid is crossed with hexane wash) DMF(100ml) in the solution.At 5 ℃, stirred again 30 minutes, mixture is warmed to room temperature in several hrs, leave standstill a night then.Reactant is poured in the water, used extracted with diethyl ether.Water layer is with the watery hydrochloric acid acidifying and use extracted with diethyl ether.With the ether extraction liquid drying, evaporate, obtain 3-hydroxyl-2-(2-(3-hydroxy methyl phenyloxy) phenyl of orange oily) methyl acrylate crude product (32.19 gram).At 5-10 ℃, with this methyl esters crude product (32.10 gram) at DMF(80ml) in stir with potash (25.4 gram), in 10 minutes to the DMF(20ml that wherein is added dropwise to dimethyl suflfate (11.6 gram)) solution.Mixture was warmed to room temperature in several hours, leave standstill a night then.Reactant is poured in the water, used the watery hydrochloric acid acidifying, extracted with diethyl ether.Ethereal extract washes with water, drying, and evaporation obtains tenne grease (14.38 gram).Use the HPLC purifying, obtain (E)-3-methoxyl group-2-(2-(3-hydroxy methyl phenyloxy) phenyl) methyl acrylate, be slightly pinkish crystalline solid (7.8 gram).
1Hn.m.r.（270MHz）δ：2.55（1H，S），3.58（3H，S），3.74（3H，S），4.55（2H，S），6.8-7.28（8H，m），7.44（1H，S）ppm。
IR maximum peak (atoleine): 3515,1705,1625Cm -1
Getting a part should alcohol (0.314 gram), stirs in the carrene (5ml) of drying in, adds dichromic acid pyridine (0.564 restrains), and mixture stirred under room temperature 4 hours.Then mixture is filtered, use the ether washing precipitate.With the carrene and the evaporation of ether cleaning solution of collecting, obtain (E)-3-methoxyl group-2-(2-(3-formyl phenoxy group) phenyl of brown oily) methyl acrylate (0.309 gram).
1Hn.m.r.（270MHz）δ：3.59（3H，S），3.65（3H，S），6.98（1H，d），7.17-7.36（4H，m），7.40-7.47（3H，m），7.47（1H，S），7.55（1H，d）ppm。
IR maximum peak (film): 1710,1640Cm -1
With (E)-3-methoxyl group-2-(2-(3-formyl phenoxy group) phenyl) methyl acrylate (0.50 gram) is at-20 ℃, in the nitrogen atmosphere, in the oxolane (20ml) of drying, stir, with phenyl-magnesium-bromide (0.53ml, the 3M diethyl ether solution) weak solution in dry THF (5ml) is added drop-wise in the above-mentioned solution at leisure, after adding ,-20 ℃ of stirring reactions 30 minutes, in 1 hour, slowly be warmed to room temperature then, leave standstill a night.Then this mixture is chilled to 5 ℃, adds entry, the mixture ethyl acetate extraction that obtains is used the salt water washing, and drying obtains a kind of yellow oil with this ethyl acetate solution evaporation.With HPLC(elutriant hexane: ether, 2: 1) purifying, obtain the compound (0.340 gram) of colorless oil desire preparation.
1Hn.m.r.（400MHz）δ：2.30（1H，d），3.57（3H，S），3.72（3H，S），5.78（1H，d），6.82（1H，d），6.91（1H，d），7.02-7.08（2H，m），7.10-7.16（1H，m），7.20-7.38（8H，m），7.45（1H，S）ppm。
IR maximum peak (film): 3460,1715,1635Cm -1
Embodiment 18
Present embodiment explanation (E)-3-methoxyl group-2-(2-(3-(2-pyridine oxygen ylmethyl) phenoxy group) preparation method's (table II compound 6) of methyl acrylate phenyl).
Silver carbonate (0.28 gram) is joined (E)-3-methoxyl group-2-(2-(the 3-bromomethyl phenoxy group) phenyl in hexane) methyl acrylate (0.75 gram, purity 70%, press the described methods preparation of embodiment 8) and 2-pyridone (0.19 restrains) in, mixture refluxed 3 hours with metal forming parcel lucifuge, left standstill a night then.Boil off hexane, residue is dissolved in the carrene, filters through C salt.Filtrate is washed with sodium bicarbonate aqueous solution, washes with water then, and drying, evaporation obtains orange jelly (0.72 gram), and purifying with HPLC, (elutriant 1: 1, ether: hexane), the desire that obtains colourless glue prepares compound (0.188 gram).
1Hn.m.r.（270MHz）δ：3.60（3H，S），3.76（3H，S），5.32（2H，S），6.78（1H，d），6.84-6.96（3H，m），7.04-7.16（3H，m），7.21-7.31（3H，m），7.48（1H，S），7.52-7.60（1H，m），8.15（1H，d）ppm。
IR maximum peak (film): 1715,1670,1645,1600Cm -1
Embodiment 19
Present embodiment explanation (E)-3-methoxyl group-2-(2-(3-pyrimidine-2-oxygen ylmethyl phenoxy group) phenyl) preparation method of methyl acrylate (table II compound 85).
With (E)-3-methoxyl group-2-(2-(3-hydroxymethyl phenoxy group) phenyl) methyl acrylate (0.5 gram, by the described methods preparation of embodiment 17) several milliliters of dry DMF() solution at room temperature joins sodium hydride (0.072 gram of stirring, 60% oily dispersion liquid was washed with hexane) dry DMF(10ml) in the suspension.After adding, mixture was stirred 5 minutes, add 2-Chloropyrimide (0.92 gram) then, place a night.Be poured into then in the water, acidifying is also used extracted with diethyl ether.With the ether extraction liquid drying, evaporation obtains yellow oil (0.95 gram), obtains the pure desire of oily with HPLC purification (elutriant ethyl acetate: hexane, 1: 1) and prepares compound (0.104 gram).
1Hn.m.r.（270MHz）δ：3.60（3H，S），3.75（3H，S），5.39（2H，S），6.86-6.96（3H，m），7.03-7.31（6H，m），7.49（1H，S），8.50（2H，d）ppm。
IR maximum peak (film): 1713,1640Cm -1
Embodiment 20
Present embodiment explanation (E, E)-and (E, Z)-3-methoxyl group-2-(2-(3-(4-nitrostyrolene base) phenoxy group) phenyl) preparation method's (table I mixture 403) of methyl acrylate.
Dry DMF(5ml with dimethylphosphite (1.39 gram)) solution at 20 ℃, is added drop-wise to the dry DMF(10ml of the sodium hydride (0.61 gram, 50% oily dispersion liquid was washed with hexane) of stirring) in the suspension.Add the back and continue to stir 20 minutes, be added dropwise to (E)-3-methoxyl group-2-(2-(3-bromomethyl phenoxy group) phenyl) methyl acrylate (7.0 grams, purity is 70% raw material, presses embodiment 8 described method preparations).Reactant mixture was placed 60 hours, 55 ℃ of heating 10 hours, poured into then in the water then, used ethyl acetate extraction.With the extract drying; evaporation; obtain the yellow jelly of thickness, obtain almost colourless oily phosphonate ester (E)-3-methoxyl group-2-(3-(diformazan (phosphonomethyl)) phenoxy group with flash chromatography method purification (elutriant is the ethyl acetate solution that contains 5% methyl alcohol)) phenylacrylic acid methyl esters (1.50 gram).
1Hn.m.r.（400MHz）δ：3.13（2H，d），3.62（3H，S），3.66（3H，S），3.68（3H，S），3.78（3H，S），6.85（1H，d），6.92（2H，d），7.00（1H，d），7.13（1H，t），7.20-7.31（4H，m），7.48（1H，S）ppm。
IR maximum peak (film): 1715,1645Cm -1
At 5 ℃, in the nitrogen atmosphere, with this phosphonate ester (0.61 gram) at dry DME(5ml) in drips of solution be added to the dry DME(10ml of the sodium hydride (0.072 gram, 50% oily dispersion liquid was washed with hexane) of stirring) in the suspension.After adding, reactant mixture is warmed to room temperature, stirs 15 minutes.Dry DME(5ml with 4-nitrobenzaldehyde (0.227 gram)) solution slowly is added drop-wise in the above-mentioned reactant mixture, stirs a night under room temperature then.Add entry, with this mixture of extracted with diethyl ether, ether phase drying is evaporated, and obtains the yellow oil of thickness, with HPLC purification (elutriant hexane: ethyl acetate, 3: 1), obtain the compound that desire prepares, be 5: 1 (Z): (E)-1,2-talan mixture of isomers (yellow gluey, 0.20 gram).
1Hn.m.r.(270MHz) the δ data of isomer ((Z)-): 3.57(3H, S), 3.74(3H, S), 6.58(1H, d), 6.72(1H, d), 6.72-6.98(3H, m), 7.05-7.36(7H, m), 7.45(1H, S), 8.06(2H, d) ppm.
This mixture can add hot reflux in containing the toluene of micro iodine and isomerization becomes 85: 15 (E): (Z)-1, and 2-talan isomer mixture.
1Hn.m.r.(400MHz) the δ data of isomer ((E)-): 3.62(3H, S), 3.78(3H, S), 6.92-7.35(10H, m), 7.49(1H, S), 7.61(2H, d), 8.22(2H, d) ppm.
Embodiment 21
Present embodiment explanation (E)-3-methoxyl group-2-(2-(3-benzoyloxy methylphenoxy) phenyl) preparation method of methyl acrylate (table I compound 398).
With (E)-3-methoxyl group-2-(2-(3-bromomethyl phenoxy group) phenyl) methyl acrylate (0.5 gram, purity is 75% raw material, press the method preparation of embodiment 8), benzoic acid (0.13 gram) and potash (0.076 gram) at room temperature stir a night in the DMF of drying.Add entry then, mixture extracts with dilute aqueous solution of sodium bicarbonate, drying, and evaporation obtains yellow thickness grease (0.49 gram), purifies (elutriant hexane: ethyl acetate, 5: 2) with HPLC, obtains the compound (0.120 gram) of desire preparation.
1Hn.m.r.（400MHz）δ：3.60（3H，S），3.75（3H，S），5.31（2H，S），6.93（1H，d），6.96（1H，d），7.06（1H，S），7.12（1H，d），7.16（1H，d），7.44（2H，t），7.25-7.32（2H，m），7.47（1H，S），7.55（1H，d），8.05（2H，d）ppm。
Embodiment 22
Present embodiment explanation (E)-3-methoxyl group-2-(2-(3-(triphenyl phosphorus ylmethyl) phenoxy group) preparation method's (table I compound 404) of methyl acrylate bromine salt phenyl).
With (E)-3-methoxyl group-2-(2-(3-bromomethyl phenoxy group) phenyl) methyl acrylate (4.58 grams, purity is 70% raw material, press the method preparation of embodiment 8) and triphenylphosphine (2.33 gram) at room temperature in the THF(40ml of drying) in stirring 4 hours, place a night then.With the solvent evaporation, obtain the residue of thickness, itself and ether/ethyl acetate are ground, obtain the compound (4.38 gram) of white-yellowish solid shape desire preparation, fusing point 176-177 ℃.
1Hn.m.r.（270MHz）δ：3.56（3H，S），3.74（3H，S），5.28（2H，d），6.48（1H，S），6.62（1H，d），6.77（1H，d），6.97（1H，d），7.04（1H，t），7.10-7.28（3H，m），7.4（1H，S），7.54-7.80（15H，m）ppm。
Embodiment 23
Preparation method's (table I compound 18) of present embodiment explanation (E, E)-3-methoxyl group-2-(2-(3-styryl phenoxy group) phenyl) methyl acrylate.
With (E)-3-methoxyl group-2-(2-(3-(triphenyl phosphorus ylmethyl) phenoxy group) phenyl) methyl acrylate bromine salt (1.0 the gram, press the method preparation of embodiment 22) dry DMF(5ml) solution, be added drop-wise to sodium hydride (0.075 gram, 50% oily dispersion liquid, washed with hexane) dry DMF(5ml) in the solution, obtain orange solution.After hydrogen has discharged (2 hours), add the dry DMF(5ml of benzaldehyde (0.66 gram)) solution, reactant mixture at room temperature stirred 20 hours, then 60 ℃ of heating 2 hours.Add entry then, the mixture ethyl acetate extraction, with the organic extract liquid drying, evaporation, obtain yellow oil (1.3 gram), with HPLC(elutriant THF: hexane, 1: 4) purify, obtain 1: 1 mixture and corresponding (Z)-styrene base class isomer (0.362 gram) that desire prepares compound.
This (Z) and (E) mixture just can be isomerizated in the reflux in toluene a few hours that contain crystallization iodine and be (E)-isomer, (the E)-isomer that obtains is colourless jelly.
1Hn.m.r.（270MHz）δ：3.64（3H，S），3.77（3H，S），6.88（1H，d），6.96-7.40（10H，m），7.49（1H，S），7.48（2H，m）ppm。
IR maximum peak (film): 1710,1640Cm -1
Embodiment 24
Present embodiment explanation (E)-3-methoxyl group-2-(2-(3-phenyloxycarbonyl phenoxy group) phenyl) preparation method of methyl acrylate (table I compound 50).
At 5-10 ℃, stir down, to (E)-3-methoxyl group-2-(2-(3-hydroxy methyl phenyloxy) phenyl) methyl acrylate (2.43 grams, press the described methods preparation of embodiment 17) acetone (100ml) solution in, add chromic acid (chromium trioxide (6.5 gram) is dissolved in the 18.5ml water that contains the 5.5ml concentrated sulfuric acid), till rufous did not take off, GC the analysis showed that initial alcohol compound all disappears.Mixture is poured in the water, used extracted with diethyl ether.Ether extraction liquid washes with water, and drying is evaporated, and obtains (E)-3-methoxyl group-2-(2-(3-carboxyl phenoxy group) phenyl of faint yellow oily) methyl acrylate (2.495 gram).
1Hn.m.r.（270MHz）δ：3.60（3H，S），3.76（3H，S），6.95（1H，d），7.14-7.40（5H，m），7.50（1H，S），7.66（1H，S），7.78（1H，d），9.35（1H，brs）ppm。
IR maximum peak (film): 3500-2500,1725,1640Cm -1
Stir down; the carboxylic acid that will obtain in the above-mentioned steps in the dry THF (10ml) (0.33 gram) is handled with ethanedioly chloride (0.11ml) and the dry DMF of a drip-dry; reactant mixture stirred 45 minutes; place a night, obtain (E)-3-methoxyl group-2-(2-(3-chloro carbonic acyl radical phenoxy group) phenyl of orange-yellow oily after the evaporation) the methyl acrylate crude product.
IR maximum peak (film): 1760,1715,1640Cm -1
Add phenol (0.090 gram) and the mixture of triethylamine (0.096 gram) in dry THF (5ml) in the acyl chlorides that above-mentioned steps in dry THF (15ml) obtains.Reactant mixture at room temperature stirred 1.5 hours, poured into then in the water, used extracted with diethyl ether, and ether extraction liquid washs with diluted sodium hydroxide solution, wash with water then, and drying, evaporation, the desire that obtains orange oily prepares compound (136 milligrams).
1Hn.m.r.（270MHz）δ：3.60（3H，S），3.77（3H，S），6.94（1H，d），7.14（2H，t），7.23-7.38（3H，m），7.47（1H，S），7.61（1H，t），7.72（1H，d）ppm。
IR maximum peak (film): 1755,1710,1640Cm -1
Embodiment 25
Present embodiment explanation (E)-2-(2-(3-(6-Chloropyrimide-4-oxygen base) phenoxy group) phenyl)-preparation method's (table II compound 89) of 3-methoxy-methyl acrylate.
With potash (0.46 gram), stannous chloride (0.027 gram) and 4.6-dichloro-pyrimidine (0.41 gram) join (E)-2-(2-(3-hydroxyphenoxy) phenyl that is stirring successively)-3-methoxy-methyl acrylate (1.0 grams, press the method preparation of embodiment 1) DMF(10ml) in the solution, the gained mixture at room temperature stirred 10 hours.The mixture dilute with water is used extracted with diethyl ether.Extract is used sodium bicarbonate aqueous solution and water washing successively, and drying concentrates, and use ether: hexane (1: 1) mixture is made elutriant, carries out chromatography and separates, and the desire that obtains colorless oil prepares compound (0.39 gram, productive rate 28%).
1Hn.m.r.（270MHz）δ：3.60（3H，S），3.76（3H，S），6.74（1H，t），6.81（1H，dd），6.90（2H，m），7.03（1H，m），7.17（1H，t），7.26-7.36（3H，m），7.49（1H，S），8.59（1H，S）ppm。
Embodiment 26
Present embodiment explanation (E)-3-methoxyl group-2-(2-(3-pyrimidine-4-oxygen phenoxyl) phenyl) preparation method of methyl acrylate (table II compound 92).
Be added dropwise to (E)-2-(2-(3-(6-Chloropyrimide-4-oxygen base) phenoxy group) phenyl under water (5ml) solution stirring with sodium hypophosphite (0.27 gram))-3-methoxy-methyl acrylate (0.4 gram, as the preparation of the method for embodiment 25), the carbon loaded article (0.08 restrains) of potash (0.2 gram) and 5% palladium is at THF(4ml) in mixed liquor in.The mixture of gained stirred under room temperature 2 hours, filtered through " Hai Fuluo " (' HYflo ') then, with ethyl acetate and water flushing.Filtrate and the cleaning solution collected are divided into water and organic facies, and latter's drying concentrates, and makes elutriant with 1: 1 mixed liquor of ether and hexane, carries out chromatography and separates, and the desire that obtains colorless oil prepares compound (0.19 gram, productive rate 52%).
1Hn.m.r.（270MHz）δ：3.61（3H，S），3.75（3H，S），6.75（1H，t），7.48（1H，S），8.56（1H，d），8.76（1H，S）ppm。
Embodiment 27
Present embodiment explanation (E)-3-methoxyl group-2-(2-(3-(3-nitro-phenoxy) phenoxy group) phenyl) preparation method of methyl acrylate (table I compound 132).
With the 3-(3-nitro-phenoxy) phenol (1.7 gram), (E)-2-(2-bromo phenyl)-3-methoxy-methyl acrylate (2.0 grams, press embodiment 13 methods preparations), the mixture of potash (1.0 gram) and stannous chloride (1.0 restrain) was 170-180 ℃ of heated and stirred 5 hours, place cooling then, this mixture of dilute with water also uses extracted with diethyl ether, extract to use sodium hydrate aqueous solution and salt water washing successively, and is dry then, concentrate, obtain the oil (3.12 gram) of brown.Ether (up to 20%) with various different proportions is made elutriant with the hexane mixed liquor, carries out chromatography and separates, and the desire that obtains yellow oily prepares compound (1.06 grams, productive rate 34%).
1Hn.m.r.（270MHz）δ：3.60（3H，S），3.76（3H，S），6.66-6.83（3H，m），7.02（1H，d），7.18（1H，d），7.22-7.38（3H，m），7.45-7.52（1H，m），7.49（1H，S），7.78（1H，m），7.92-7.97（1H，m）ppm。
Embodiment 28
Present embodiment explanation (E)-3-methoxyl group-2-(2-(3-(3-methoxyl group phenoxymethyl) phenoxy group) preparation method's (table I compound 372) of methyl acrylate phenyl).
With (E)-3-methoxyl group-2-(2-(3-methylphenoxy) phenyl) methyl acrylate (0.50 gram, press the method preparation of embodiment 8), 1,3-two bromo-5,5-dimethyl hydantoin (0.32 gram) and azodiisobutyronitrile (0.033 gram) add hot reflux in carbon tetrachloride (40ml), simultaneously, with 400 watts of tungsten lamp irradiations.React after one hour mixture is cooled off, pour in the water.Organic phase solution is isolated, wash with water, drying, evaporation obtains yellow toughening oil (0.825 gram), wherein contain (E)-3-methoxyl group-2-(2-(3-bromomethyl phenoxy group) phenyl of about 65%) methyl acrylate, do not need further purification to use and (see among the embodiment 8 1Hn.m.r. data).
With above-mentioned bromide crude product (0.41 gram) at dry DMF(4ml) in solution join the dry DMF(6ml of 3-metoxyphenol sodium (by 3-metoxyphenol and sodium hydride preparation)) in the solution, stirred 4 hours, place a night then.Reactant is poured in the aqueous solution of watery hydrochloric acid, uses ethyl acetate extraction.With the organic fraction drying, evaporation obtains brown oil.Purify (40/60 benzinum: ethyl acetate is 7: 3 elutriant) with HPLC, the desire that obtains colourless glue prepares compound (0.20 gram).
IR maximum peak (film): 1715,1640Cm -1
1Hn.m.r.（400MHz）δ：3.60（3H，S），3.73（3H，S），3.77（3H，S），4.99（2H，S），6.50-6.55（3H，m），6.88-6.95（2H，m），7.05（1H，S），7.09-7.20（3H，m），
7.24-7.31（3H，m），7.47（1H，S）ppm。
Embodiment 29
Present embodiment explanation (E)-3-methoxyl group-2-(2-(3-benzoyl phenoxy group) phenyl) preparation method of methyl acrylate (table I compound 12).
With the 2-(3-hydroxy methyl phenyloxy) methyl phenylacetate (10.0 grams, the method preparation of pressing embodiment 17) and C salt (10 gram) mixing in carrene (100ml), disposable adding chloro-chromic acid pyridine (15.85 gram).At room temperature stirred 2.5 hours, mixture is filtered, the filtrate evaporation obtains the 2-(3-formyl phenoxy group of orange oily) methyl phenylacetate (8.48 gram), do not need further purification to use.
IR maximum peak (film): 1740,1700Cm -1
1Hn.m.r.（270MHz）δ：3.59（3H，S），3.69（2H，S），6.92（1H，d），7.14-7.20（1H，t），7.23-7.37（3H，m），7.43（1H，m），7.50（1H，t），7.60（1H，dd），9.95（1H，S）ppm。
Phenyl-magnesium-bromide (the 3M diethyl ether solution of 2.84ml) is added drop-wise in the THF solution of the above-mentioned aldehyde (2.30 gram) that stirs of being cooled, reaction temperature is no more than-30 ℃.After adding (35 minutes), reactant mixture slowly is heated to room temperature, stirs a night, adds entry at ice bath carefully to cold condition then.Add watery hydrochloric acid then, the mixture ethyl acetate extraction.With the extract drying, evaporation obtains yellow oil, purifies (hexane: ethyl acetate is 2: 1 eluent) with the flash chromatography method, obtains 2-((3-(2-hydroxyl) benzyl) phenoxy group of faint yellow oily) methyl phenylacetate (1.69 gram).
1Hn.m.r.（270MHz）δ：3.57（3H，S），3.68（2H，S），5.79（1H，S），6.79-6.90（2H，m），
7.05-7.13（3H，m），7.18-7.40（9H，m）ppm。
At room temperature, the hydroxy ester of above-mentioned preparation (0.91 gram) is stirred in carrene (25ml) with two spoonfuls of C salt, add pyridinium chlorochromate (0.65 restrains) then, reactant stirring 3 hours.Mixture filters, and the filtrate evaporation with HPLC purifying (hexane: ethyl acetate is that 3: 1 mixture is made elutriant), obtains the 2-(3-benzoyl phenoxy group of faint yellow glue) methyl phenylacetate (0.56 gram).
1Hn.m.r.（270MHz）δ：3.60（3H，S），3.70（2H，S），6.93（1H，d），7.10-7.63（10H，m），7.81（2H，d）ppm。
IR maximum peak (film): 1740,1660Cm -1
This raw material is pressed the method for the described similar two step conversion reactions of embodiment 7, with sodium hydride and methyl formate, handles with potash and dimethyl suflfate then, is converted into the compound of desire preparation.
IR maximum peak (film): 1710,1660,1635Cm -1
1Hn.m.r.（270MHz）δ：3.60（3H，S），3.75（3H，S），6.98（1H，d），7.12-7.20（2H，m），7.26-7.52（8H，m），7.47（1H，S），7.55-7.63（1H，m），7.80（2H，dd）ppm。
Embodiment 30
Present embodiment explanation (E)-3-methoxyl group-2-(2-(3-benzyl phenoxy group) phenyl) preparation method of methyl acrylate (table I compound 9).
Under 5 ℃ of stirrings, trifluoroacetic acid (3.28 gram) is dropped to 2-((3-(Alpha-hydroxy) benzyl) phenoxy group) in the methyl phenylacetate (1.68 grams, the method for press embodiment 29 prepares).After adding, slowly be added dropwise to triethyl silicane (2.24 gram) again.Then the gained clear liquid is stirred a night, dilute with water is used extracted with diethyl ether.Ether extraction liquid washs with sodium bicarbonate aqueous solution, and drying concentrates and purifies (hexane: ether is 4: 1 a elutriant) with HPLC, obtains colorless oil 2-(3-benzyl phenoxy group) methyl phenylacetate (1.03 gram).
IR maximum peak (film): 1742Cm -1
This raw material is pressed the two-step method of embodiment 7 described similar conversion reactions, with sodium hydride and methyl formate, handles with potash and dimethyl suflfate then, is converted into desire and prepares compound.
IR maximum peak (film): 1708,1635Cm -1
1Hn.m.r.（270MHz）δ：3.56（3H，S），3.72（3H，S），3.93（2H，S），6.76-6.93（4H，m），7.08-7.31（10H，m），7.47（1H，S）ppm。
Embodiment 31
Present embodiment explanation (E)-3-methoxyl group-2-(2-(3-(N-phenyl sulfonamido) phenoxy group) phenyl) preparation method of methyl acrylate (table I compound 78).
With 2-bromobenzene acetate (21.5 gram), 3-nitrophenol (29.2 gram), the mixture of potash (27.6 gram) and stannous chloride (0.5 restrains) was 130 ℃ of heated and stirred 6 hours.After the cooling, pour mixture in the water (500ml), use the concentrated hydrochloric acid acidifying, ethyl acetate extraction (3 * 200ml).The extract drying is filtered, and concentrates, and obtains black oil.This oil is dissolved in the methyl alcohol (400ml) that contains the concentrated sulfuric acid (4ml), with gained vlil 3 hours.Concentrated reaction mixture, residue are dissolved in the ethyl acetate (300ml), and this solution is used sodium hydroxide (the 1M aqueous solution of 2 * 100ml) and salt water washing successively, and be dry then, filters, and concentrates and obtain black oil.Bubbling distills this oil (temperature is 220 ℃, 0.2mmHg), obtains the 2-(3-nitro-phenoxy of limpid pale oily) methyl phenylacetate (16.74 grams, calculating productive rate from 2-bromobenzene acetate is 58%).
1Hn.m.r.（270MHz）δ：3.60（3H，S），3.70（2H，S），6.9-8.0（8H，m）ppm。
IR maximum peak (film): 1739Cm -1
Under agitation, with the 2-(3-nitro-phenoxy) methyl phenylacetate (15 gram), methyl alcohol (100ml), the mixture of glacial acetic acid (100ml) and iron powder (15.0 gram) slowly is heated to backflow.After 30 minutes,, filter excessive iron powder with the mixture cooling.Filtrate is poured in the water (700ml), with ether (2 * 200ml) extractions.Stir down, ether extraction liquid neutralizes with sodium bicarbonate aqueous solution, and is dry then, filters, and concentrates the 2-(3-amino-benzene oxygen that obtains faint yellow oily) methyl phenylacetate (13.0 grams, productive rate 97%).
1Hn.m.r.（270MHz）δ：3.63（3H，S），3.68（2H，S），3.9（1H，brs），6.2-7.3（8H，m）ppm。
IR maximum peak (film): 3400,3373,1733Cm -1
Be chilled at water under the condition of (effervesce) below 10 ℃, with the 2-(3-amino-benzene oxygen) methyl phenylacetate (11.54 gram) and methyl formate (27.7ml) be at DMF(25ml) in mixed liquor be added drop-wise to the DMF(50ml of sodium hydride (3.25 restrain)) in the stirred suspension.After adding, reactant mixture was stirred under room temperature 3 hours, pour in the water, use the concentrated hydrochloric acid acidifying, use ethyl acetate extraction.Extract salt water washing, drying concentrates the yellow oil that obtains thickness.Potash (12.4 gram) and dimethyl suflfate (4.25ml) being added to successively the DMF(50ml of this yellow oil) in the agitating solution, the gained mixture at room temperature stirred 3 hours, poured in the water, used ethyl acetate extraction.Extract is through washing, and drying concentrates green jelly (the E)-2-that obtains becoming clear (2-(3-formamido phenoxy group) phenyl)-3-methoxy-methyl acrylate (13.67 grams, productive rate 93%).
1Hn.m.r.（270MHz）δ：3.60（3H，S），3.78（3H，S），4.47（1H，S）ppm。
IR maximum peak (film): 3309,1702,1606Cm -1
Phosphoryl chloride phosphorus oxychloride (7.8ml) is added drop-wise to (E)-2-(2-(3-formamido phenoxy group) phenyl)-methyl alcohol (100ml) agitating solution of 3-methoxy-methyl acrylate (13.67 gram) in, the temperature when dripping with cryostat control is lower than 50 ℃.Stir after 20 minutes, reactant is poured in the water (500ml), with sodium bicarbonate neutralization, extracted with diethyl ether, with the extract drying, concentrates, and obtains yellow oil.Make the elutriant chromatography with ether and separate this oil, obtain (E)-2-(2-(3-amino-benzene oxygen) phenyl)-3-methoxy-methyl acrylate (8.57 grams, productive rate 68%), be yellow solid, fusing point 83-85 ℃.
1Hn.m.r.（270MHz）δ：3.6（2H，brs），3.62（3H，S），3.77（3H，S），6.2-6.4（3H，m），6.9-7.3（5H，m），7.48（1H，S）ppm。
IR maximum peak (film): 3450,3370,1703,1632Cm -1
At-10 ℃, handle (E)-2-(2-(3-amino-benzene oxygen) phenyl with 5.8M hydrochloric acid (1ml))-glacial acetic acid (2ml) solution of 3-methoxy-methyl acrylate (0.4 gram).Still at-10 ℃, handle above-mentioned agitating solution then with natrium nitrosum (0.1 gram is in 2ml water).After 30 minutes, above-mentioned solution (containing diazol) is added to contains 0.1 gram stannous chloride, in being stirred the mixture by the saturated glacial acetic acid of sulphur dioxide (0.5ml) (effervesce).After 30 minutes, pour into reactant in the water and use extracted with diethyl ether.Ether extraction liquid neutralizes with saturated sodium bicarbonate aqueous solution, and drying concentrates, and obtains (E)-2-(2-(3-chlorosulfonyl phenoxy group) phenyl of yellow oily)-3-methoxy-methyl acrylate (0.14 gram).
IR maximum peak (film): 1710,1636Cm -1
At room temperature, in 2-(2-(3-chlorosulfonyl phenoxy group) phenyl)-pyridine (0.5ml) solution of 3-methoxy-methyl acrylate (0.14 gram) in, drip aniline (0.05ml) and carry out stir process.After 3 hours, reactant is poured in the water, added the hydrochloric acid of 2M, slightly be acid, use extracted with diethyl ether to this solution.Ether extraction liquid is through the salt water washing, and drying concentrates, and carries out chromatography with ether as elutriant and separates, and the desire that obtains limpid oily prepares compound (0.145 gram).
IR maximum peak (film): 3240,1693,1635,1600Cm -1
1Hn.m.r.（270MHz）δ：3.55（3H，S），3.69（3H，S），6.53（1H，brs），6.8（1H，m），7.0-7.4（12H，m），7.43（1H，S）ppm。
Embodiment 32
Present embodiment explanation (E)-2-(2-(3-(3-bromobenzene amide groups) phenoxy group) phenyl)-preparation method's (table I compound 421) of 3-methoxy-methyl acrylate.
3-bromobenzene formyl chloride (0.37 gram) is added (E)-2-(2-(3-amino-benzene oxygen) phenyl that stirs)-carrene (20ml) solution (containing triethylamine 0.17 restrains) of 3-methoxy-methyl acrylate (0.5 gram is by the method preparation of embodiment 31) in.After 3 hours, reactant is poured in the water, with carrene (2 * 50ml) extractions.The extract drying concentrates, and carries out chromatography with ether as elutriant and separates, and obtains desire and prepares compound (0.61 gram), is the weak yellow foam body.
IR maximum peak (atoleine): 1710,1680,1640,1605Cm -1
1Hn.m.r.（270MHz）δ：3.62（3H，S），3.78（3H，S），6.73-8.0（13H，m），7.47（1H，S）ppm。
Embodiment 33
Present embodiment explanation (E)-2-(2-(3-pyridine-2-oxygen phenoxyl) phenyl)-preparation method's (table II compound 1) of 3-methoxy-methyl acrylate.
With potash (0.92 gram), stannous chloride (catalytic amount), bronze (catalytic amount) and 2-fluorine pyridine (1.94 gram) join (E)-2-(2-(3-hydroxyphenoxy) phenyl successively)-DMF(15ml of 3-methoxy-methyl acrylate (2.0 grams, the method for pressing embodiment 1 prepares)) in the agitating solution.This mixture was stirred 3 hours at 130 ℃.After the cooling, this mixture of dilute with water, and with extracted with diethyl ether (* 2), the extract of collection is used sodium hydrate aqueous solution successively, water and salt water washing, dry then and concentrate.Carry out chromatography with ether-hexanes mixtures as elutriant and separate, obtain a kind of desire and prepare compound orange-yellow gummy oil (1.68 grams, productive rate 67%).
1Hn.m.r.（270MHz）δ：3.60（3H，S），3.73（3H，S），6.72-7.32（10H，m），7.48（1H，S），7.67（1H，m），8.19（1H，m）ppm。
Embodiment 34
Present embodiment explanation (E)-2-(2-(3-(6-chlorine pyridazine-3-oxygen base) phenoxy group) phenyl)-preparation method's (table II compound 130) of 3-methoxy-methyl acrylate.
With potash (0.93 gram), stannous chloride (catalytic amount) and 3,6-dichloro-pyridazine (1.0 gram) joins (E)-2-(2-(3-hydroxyphenoxy) phenyl successively)-DMF(30ml of 3-methoxy-methyl acrylate (2.01 grams, the method for press embodiment 1 prepares)) in the agitating solution.The mixture that obtains stirred 1 3/4 hours at 95 ℃, after the cooling, and dilute with water, extracted with diethyl ether (* 2).The extract of collecting is used sodium hydrate aqueous solution successively, and water and salt water washing are dry then, concentrate.Carry out chromatography with ether-hexanes mixtures as elutriant and separate, obtain yellow gluey desire and prepare compound (1.71 grams, productive rate 62%).
1Hn.m.r.（270MHz）δ：3.60（3H，S），3.73（3H，S），6.73-7.36（9H，m），7.46（1H，m），7.50（1H，S）ppm。
Below be the embodiment of the composition that is suitable for agricultural and gardening aspect application that is mixed with by compound of the present invention.This composition forms another aspect of the present invention.The employing percetage by weight is represented.
Embodiment 35
By following component being mixed and being stirred to whole dissolvings, prepare a kind of emulsible concentrate.
Table I compound 212 10%
Phenmethylol 30%
Calcium dodecyl benzene sulfonate 5%
Nonyl phenol ethoxylate
(13 moles of ethylene oxide) 10%
Alkylbenzene 45%
Embodiment 36
Active constituent is dissolved in carrene, the gained spray liquid to the particle of atlapulgite, is made the solvent evaporation then, make granular composition.
Table I compound 212 5%
Atlapulgite 95%
Embodiment 37
By grinding and mixing following three kinds of components, prepare a kind of composition that can be used for dressing seed.
Table I compound 212 50%
Mineral oil 2%
Potter's clay 48%
Embodiment 38
By with active constituent and talcum ground and mixed, prepare a kind of superfine powder.
Table I compound 212 5%
Talcum 95%
Embodiment 39
By with each component and water for ball milling, form the water slurry of levigate mixture, make a kind of suspension-concentrates.
Table I compound 212 40%
Sodium lignosulfonate 10%
Bentonite 1%
Water 49%
Can be used as a kind of spray behind the said preparation dilute with water and use, or directly apply to seed.
Embodiment 40
By following each component is mixed, be ground to abundant mixing, prepare a kind of wettable powder formulation.
Table I compound 212 25%
Lauryl sodium sulfate 2%
Sodium lignosulfonate 5%
Silica 25%
Potter's clay 43%
Embodiment 41
The test all cpds is to the effect of the mould bacterial diseases of various leaves of plant, and the method that is adopted is as follows:
In John Yin Dynasty how in this canned compost (John Innes Potting Compost) No. 1 or No. 2, the diameter of canister is 4Cm with plant species.Compound to be tested or be made into preparation with moisture T dispersion agent (Dispersol T) ball milling perhaps before use, is diluted to the solution of desired concn with acetone or acetone.To the test of leaf disease, preparaton (all using the 100ppm active constituent except as otherwise noted) is sprayed onto on the plant leaf, and is administered to plant root in the soil.Sprinkling reaches maximum retention, and the ultimate density that root soaks into is approximately 40ppm active ingredient/dry ground earth.When spray is applied to cereal, add polysorbas20 (Tween2o), its ultimate density reaches 0.05%.
To the great majority test, be inoculated the preceding a couple of days of disease plant, compound is applied on soil (root) and the leaf (spraying).What make an exception is when Erysiphe graminis is tested, earlier plant to be inoculated in handling preceding 24 hours.By introducing the leaf cause of disease on the leaf that spore suspension is sprayed onto test plant.After the inoculation, plant is put into suitable environment, make to infect and proceed and obtain to cultivate, up to being suitable for checking the disease situation.Different according to the disease of different situations and environment changed in fortnight at four days from the time interval that is inoculated into check.
The situation of disease control is pressed following grade record:
4=does not have disease
3=be untreated plant the rate of falling ill for the trace～5%
The be untreated rate of falling ill of plant of 2=is 6-25%
The be untreated rate of falling ill of plant of 1=is 26-59%
The be untreated rate of falling ill of plant of 0=is 60-100%
The results are shown in the table VI.
Figure 881072702_IMG81
Figure 881072702_IMG82
Figure 881072702_IMG83
Figure 881072702_IMG84
Figure 881072702_IMG85
Figure 881072702_IMG86
Figure 881072702_IMG87
Figure 881072702_IMG89

Claims (6)

1, a kind of Fungicidal composition, said composition contain the antifungal effective dose fungicide active ingredient and can be in fungicide application carrier or thinner, it is characterized in that this Fungicidal active ingredient is formula (I) compound shown below and its stereoisomer
Figure 881072702_IMG2
Wherein:
K is oxygen or sulphur;
Z is phenyl, naphthyl or heteroaryl;
Heteroaryl wherein is by selecting in the following heteroaryl group: pyridine radicals, pyrimidine radicals, pyrazinyl, pyridazinyl, triazinyl, triazolyl, thienyl, furyl, pyrrole radicals, thiazolyl, oxazolyl, oxadiazole base, thiatriazole base, quinolyl, isoquinolyl, quinazolyl, quinoxalinyl, benzothienyl, benzoxazole, benzothiazolyl, purine radicals or Thienopyrimidine base, and the corresponding oxide of suitable they, the phenyl in the formula, naphthyl or heteroaryl moieties can be replaced by one or more following substituting groups: hydroxyl, halogen, C 1-4-alkyl, C 1-4-alkoxyl, C 1-4-alkylthio group, nitro, cyano group, halo (C 1-4) alkyl, halo (C 1-4) alkoxyl, phenyl, phenoxy group, C 1-4Alkanoyloxy, NHCOR 6, NHSO 2NR 6, NR 7R 8, CONR 7R 8, CO 2R 7(R wherein 6Be C 1-4Alkyl or phenyl and R 7And R 8Be H or C independently of one another 1-4Alkyl), CH 3O 2C-C=CH-OCH 3Or two adjacent substituting group combinations are to form a phenyl ring that condenses or pyridine ring;
X is O, S (O) n(wherein n is 0,1 or 2), NH, NCH 3, NCH 2CH 3, NCOCH 3, NCH (CH 3) 2, CH 2, CH (CH 3), C (CH 3) 2, CO, C=CH 2, C=C (CH 3) 2, CH 2CH 2, CH (CH 3) CH 2, CH 2CH (CH 3), ( E)-CH=CH, ( Z)-CH=CH, ( E)-C (CH 3)=C (CH 3), C ≡ C, OCH 2, OCH (CH 3), (CH 2) pO (wherein P is an integer of 1 to 5), CH (CH 3) O, SCH 2, SCH (CH 3), S (O) CH 2, S (O) CH 2, S (O) CH (CH 3), S (O) 2CH 2, S (O) 2CH (CH 3), CH 2S, CH (CH 3) S, CH 2S (O), CH (CH 3) S (O), CH 2S (O), CH (CH 3) S (O) 2, NHCH 2, N (CH 3) CH 2, N (COCH 3) CH 2, NHCH (CH 3), N (CH 3) CH (CH 3), N (COCH 3) CH (CH 3), CH 2NH, CH 2N (CH 3), CH 2N (COCH 3), CH (CH 3) NH, CH (CH 3) N (CH 3), CH (CH 3) N (COCH 3), CO 2, O 2O, SO 2C, OSO 2, COCO, COCH 2, COCH (CH 3), CH 2CO, CH (CH 3) CO, CH (OH) CH 2, CH (OH) CH (CH 3), CH 2CH (OH), CH (CH 3) CH (OH), CONH, CON (CH 3), CON (CH 2CH 2CH 3), CON (CHO), CON (COCH 3), NHCO, N (CH 3) CO, N (CH 2CH 3) CO, N (CHO) CO, N (COCH 3) CO, CSN (CH 3), CSNH, NHCS, N (CH 3) CS, SO 2NH, SO 2N (CH 3), NHSO 2, N (CH 3) SO 2, N (CH 2CH 3) SO 2, CS 2, S 2C, COS, SCO, ( E)-N=N, ( E)-N=CH, ( E)-N=C (CH 3), ( E)-CH 2=N, ( E)-C (CH 3)=N, CH 2CH 2CH 2, CH (CH 3) CH 2CH 2, CH 2CH (CH 3) CH 2, CH 2CH 2CH (CH 3), OCH 2CH 2, CH 2OCH 2, SCH 2, CH 2, S (O) CH 2CH 2, S (O) 2CH 2CH 2, CH 2SCH 2, CH 2S (O) CH 2, CH 2S (O) 2CH 2, CH 2CH 2S, CH 2CH 2S (O) CH 2CH 2S (O) 2, ( E)-CH=NNH, ( E)-C (CH 3)=NNH, ( E)-CH=NH (CH 3), ( E)-NHN=CH, ( E)-NHN=C (CH 3), ( E)-N (CH 3) N=CH, CH 2CONH, CH (CH 3) CON (CH 3),
( E)-CH=CHCH 2O、COCH 2CH 2O、
Figure 881072702_IMG3
CH (C 6H 5), COCH 2O, CH (OH), CO 2CH 2, (C 6H 5) 2P +CH 2Br -, CH 2OCO, CH 2NHCO, CH 2SCO, OCH 2O, OCH 2CH 2O, S (O) CH2O, COCH (CH3) O, (E)-CH2ON=CH, (E)-CH2ON=CH, CH2CH2CH (OH), ( E)-CH 2CH=CH, C (CH 3) (OH), CH 2OSO 2, CH 2NHCONH, OCONH, NHCONH or CH 2OCONH,
A is hydrogen, hydroxyl, halogen, C 1-4Alkyl, C 1-4Alkoxyl, halo (C 1-4) alkyl, halo (C 1-4) alkoxyl, nitro, cyano group, acetyl group or phenoxy group;
B and E are hydrogen or halogens, and perhaps B is C 1-4-alkoxyl;
As A, B, E all be hydrogen and Z is under the condition of unsubstituted phenyl, X is not 0.
2, a kind of method for compositions for preparing claim 1, this method comprise with the sterilization effective dose, as formula (I) compound defined in claim 1 with can be in bactericide application carrier or mixing diluents.
3, according to the method for claim 2, wherein the method for the compound of preparation formula (I) comprising:
(a) use formula CH 3The compound of the compound treatment formula (II) of L:
Figure 881072702_IMG4
(b) under acidity or alkali condition from the compound of formula (IV) cancellation methyl alcohol unit
Figure 881072702_IMG5
(c) ketone ester of usefulness methoxyl group methylenation agent treated formula (VI):
Figure 881072702_IMG6
(d) in the presence of alkali, the reaction of the compound of the compound of formula (IX) and formula (X):
(e) in the presence of alkali, the reaction of the compound of the compound of formula (XI) and formula (XII):
Figure 881072702_IMG8
Wherein the definition of A, B, E, K, Z and X is as described in the claim 1, R 6Be metallic atom, L is a leaving group, and W is ZX or is CH with group and Y that standard method can be transformed into ZX subsequently 3OCH=C(CO 2CH 3) or can be transformed into the group of such group subsequently with standard method.
4, according to the method for claim 2, wherein the method for preparation formula (I) compound comprises general formula (XII a) compound and general formula (XI a) phenol or benzenethiol in the presence of alkali, react, perhaps with phenol or benzenethiol (XI a) reactant salt,
Figure 881072702_IMG9
Y in the formula 1Be halogen, the implication of E provides in claim 1.
Figure 881072702_IMG10
The implication of A, B, K, X and Z is as described in the claim 1 in the formula; More than reaction is preferably under the catalyzer existence that contains suitable transition metal, transition metal salt or compound or their mixture and carries out.
5, according to the method for claim 2, wherein the method for preparation formula (I) compound comprises (a) in the presence of alkali, the compound of formula (X III):
Figure 881072702_IMG11
React with following compounds:
(ⅰ) when X is 0, react with compound ZL; Or
(ⅱ) when X be SO 2During O, with compound ZSO 2The Q reaction; Or
(ⅲ) when X be CHR 1During O, with compound ZCHR 1The L reaction; Or
(b) in the presence of alkali, the compound of formula (X VII):
Figure 881072702_IMG12
React with following compounds:
(ⅰ) when X is S, react with compound ZL; Or
(ⅱ) when X be CHR 1During S, with compound ZCHR 1The L reaction; Or
(c) in the presence of alkali, the compound of formula (XX):
Figure 881072702_IMG13
React with following compounds:
(ⅰ) when X be OCHR 2The time, react with compound ZOH; Or
(ⅱ) when X be (R 5) 2P+CHR 2Q -When being halide, with formula Z(R with L 5) 2The phosphine reaction of P; Or
(d) when X be CR 1=CR 2The time, in the presence of alkali, the compound of formula (X XII):
With formula ZR 1The aldehydes or ketones reaction of C=0; Or
(e) when X be CR 1=CR 2The time,
(ⅰ) use formula ZR 1C -P(O) (OR) 2M +Phosphonate ester anion or the corresponding phosphorane compound of handling formula (XX III):
Figure 881072702_IMG15
(ⅱ) when X be (R 5) P +CHR 2Q -The time, the compound of formula (I) one by one with alkali and formula ZCOR 1Carbonyls reaction; Or
(f) when X be CHR 1CHR 2The time, the product of reduction (e); Or
(g) when X be CONR 4The time, the compound of formula (XX VI):
Figure 881072702_IMG16
React with following compounds:
(ⅰ) in the presence of alkali, with the acyl halide reaction of formula ZCOQ; Or
(ⅱ) in the presence of dehydrating agent, with formula ZCO 2The acid reaction of H; Or
(h) aldehydes or ketones of formula (XX III) and following compounds reaction:
Figure 881072702_IMG17
(ⅰ) X is ON=CR in the formula 2, CHR 1ON=CR 2Or NR 1N=CR 2The time, respectively with formula ZONH 2Or ZCHR 1ONH 2Hydroxylamine or with formula ZNR 1NH 2Hydrazine reaction; Or
(ⅱ) X is CR in the formula 2(OH) or CR 1R 2CR 2(OH) time, respectively with molecular formula ZMgHal or ZCHR 1That reagent reacting of the Green of MgHal; Or
(ⅲ) X is NR in the formula 10CHR 2The time, in the presence of reductant, with molecular formula ZNHR 10Amine reaction; Or
(ⅳ) X is N=CR in the formula 2Or CHR 1ON=CR 2The time, do not having in the presence of the reductant, respectively with molecular formula ZNH 2Or ZCHR 1ONH 2The amine reaction; Or
(k) X is O in the formula 2C, CHR 1OCO, SCO, CHR 1SCO, NR 4CO or CHR 1NR 4During CO,
(ⅰ) for example in the presence of dicyclohexyl carbodiimide or the carbonyl dimidazoles, in suitable solvent, handle the carboxylic acid of molecular formula (XX IX) with suitable alcohol, mercaptan or amine at the standard coupling agent:
(ⅱ) in the presence of alkali, in suitable solvent, use molecular formula ZOH respectively, ZCHR 1OH, ZSH, ZCHR 1SH, ZNR 4H or ZCHR 1NR 4The acid chloride reaction of the compound of H and formula (XXX):
Figure 881072702_IMG19
(l) X is OCHR in the formula 2The time, the compound of formula (XX VIII) and the reaction of the compound of formula ZL:
Figure 881072702_IMG20
A in the formula, B, E, K, R 1, R 2, R 4, R 5With the definition of Z as described in the claim 1, L is a leaving group, Q and Hal are halogens, R is an alkyl, R 10Be hydrogen or C 1-4Alkyl and M +It is metal ion.
6, the purposes of the Fungicidal composition of claim 1, this purposes comprises the seed that said composition is applied to plant, plant, perhaps is applied to the location of plant or seed, with the infection of control fungi.
CN 88107270 1987-09-09 1988-09-09 Fungicides Expired - Lifetime CN1021009C (en)

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