Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Ester doai
Reexamination Certificate
2002-02-07
2003-04-22
Raymond, Richard L. (Department: 1624)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Ester doai
C514S619000, C514S620000, C560S035000, C564S163000, C564S165000, C564S256000
Reexamination Certificate
active
06552080
ABSTRACT:
This application was filed under 35 U.S.C. 371, and is the U.S. national stage of PCT/KR00/00906, filed Aug. 16, 2000.
FIELD OF THE INVENTION
The present invention relates to novel fungicidal compounds having a fluorovinyl- or fluoropropenyl-oxyphenyloxime moiety, a process for preparing same and a fungicidal composition containing same as an active ingredient.
DESCRIPTION OF THE PRIOR ART
A number of fungicidal compounds have been in practical use to protect crops from various pathogenic fungi; and they may be classified into several groups according to their similar structural features. However, the repetitive use of a fungicide over a long period induces the appearance of new fungal strains resistant not only to the particular fungicide but also to related fungicides having common structural features. For this reason, continuous efforts have been undertaken to develop novel fungicides.
Such efforts have led to the development of new fungicides, e.g., propenoic esters derived from strobilurin (U.S. Pat. No. 4,994,495; WO 94/19331; U.S. Pat. No. 5,003,101) and other propenoic ester fungicides disclosed in EP A 0 278 595 (Zeneca), EP A 0 782 982 (Novatis), WO 96/33164 (Ciba-Geigy), WO 96/33164 (Rhone-Poulenc Agro), WO 98/56774 (BASF), WO 99/06379 (BASF), WO 99/23066 (Agrevo UK), German Patent Nos. 724,200 and 732,846 (both BASF), and British Patent No. 22,893 (Agrevo UK). However, these propenoic ester derivatives still have the problem of limited fungicidal activity.
SUMMARY OF THE INVENTION
Accordingly, it is a primary object of the present invention to provide a novel compound having a high fungicidal activity against a wide spectrum of plant pathogenic fungi.
It is another object of the present invention to provide a process for the preparation of said compound.
It is a further object of the present invention to provide a fungicidal composition containing said compound.
In accordance with one aspect of the present invention, there are provided a novel compound of formula (I) and stereoisomers thereof:
wherein,
X is CH or N;
Y is O or NH;
R
1
is hydrogen, C
1-4
alkyl, or halogen-substituted C
1-4
alkyl;
R
2
is a phenyl group optionally carrying one or more substituents selected from the group consisting of C
1-4
alkyl, C
1-4
alkoxy, methylenedioxy and halogen; or a naphthyl group; and
R
3
is hydrogen or CF
3
.
DETAILED DESCRIPTION OF THE INVENTION
The structure of the compound of formula (I) of the present invention is characterized by the fluorovinyl- or fluoropropenyl-oxyphenyloxime moiety, and depending on whether X is CH or N, it may also be classified as a propenoic acid derivative (X=CH) or as an iminophenylacetic acid derivative (X=N).
Among the compounds of the present invention, preferred are those wherein R
1
is hydrogen or methyl, and R
2
is phenyl group, or Cl- or F-substituted phenyl group.
The compound of formula (I) of the present invention may be prepared, as shown in Reaction Scheme A:
wherein, X, R
1
, R
2
and R
3
have the same meanings as defined in formula (I) above.
In Reaction Scheme A, the compound of formula (I-a), i.e., a compound of formula (I) wherein Y is O, may be prepared by the steps of (a) reacting a compound of formula (II) with an oxime derivative of formula (III) in the presence of a base to obtain a compound of formula (IV); (b) debenzylating the compound of formula (IV) by hydrogenolysis in the presence of a Pd(C) catalyst to obtain a compound of formula (V-a); and (c) reacting the compound of formula (V-a) with a compound of formula (VI) in the presence of a base:
The compound of formula (II) is inclusive of the compounds of formula (II-a) (X=CH) and formula (II-b) (X=N):
The compound of formula (II-a) may be prepared by esterification, formylation, methylation and bromination of o-tolylacetic acid according to a conventional method (Yamada, K. et al.,
Tetrahedron Lett
., 2745(1973); Vyas, G. N. et al.,
Org. Syn. Coll
., 4, 836(1963); Kalir, A.,
Org. Syn. Coll
., 5, 825(1973); Korean Unexamined Patent Publication Nos. 98-83587 and 99-15785; and World Patent Publication No. WO 99/07665), as shown in Reaction Scheme B:
The compound of formula (II-b) may be prepared by Grignard reaction, oxalylation, condensation, methylation and bromination of o-bromotoluene according to a conventional method (Rambaud, M. et al.,
Synthesis
, 564(1988); Korean Unexamined Patent Publication Nos. 98-83587 and 99-15785; and World Patent Publication No. WO 99/07665), as shown in Reaction Scheme C:
The compound of formula (III), on the other hand, represents, among others, the compounds of formula (III-a) (R
1
=H), formula (III-b) (R
1
=CH
3
) and formula (III-c) (R
1
=CF
3
):
The compounds of formulas (III-a), (III-b) and (III-c) may be prepared by the steps of benzylation and condensation of 3-hydroxybenzaldehyde, 3-hydroxyacetophenone and 3-hydroxy-2′2′2′-trifluoroacetophenone, respectively, in accordance with a conventional method (Kuhn, R. et al.,
Chem. Ber
. 90, 203(1957); Fletcher, H. G. et al.,
Methods Carbohydr. Chem., II
, 166(1963); Freedman, H. H., et al.,
Tetrahedron Lett
., 3251(1975); Lichtenhaler, F. W., et al.,
Tetrahedron Lett
., 1425(1980); and Sugg, E. E., et al.,
J. Org. Chem
., 50, 5032(1985)), as shown in Reaction Scheme D:
wherein, R
1
has the same meanings as defined in formula (I) above.
In the reaction to prepare the compound of formula (IV), the compound of formula (II) and the compound of formula (III) may be used in equimolar amounts and the base may be used in one or two equivalent amounts. The base may be an inorganic base, e.g., sodium hydride, potassium t-butoxide, sodium carbonate or potassium carbonate; or an organic base, e.g., triethyl amine or pyridine. The solvent which may be used in the reaction includes acetone, methyl ethyl ketone, benzene, toluene, tetrahydrofuran, acetonitrile, dichloromethane or dimethyl formamide, and the reaction may be conducted at a temperature ranging from room temperature to 100° C. The progress of the reaction is conveniently followed by measuring the disappearance of the compound of formula (II) with thin layer chromatography (TLC).
Examples of the compound of formula (IV) include the compounds of formulas (IV-a) (X=CH, R
1
=H), (IV-b) (X=CH, R
1
=CH
3
), (IV-c) (X=CH, R
1
=CF
3
), (IV-d) (X=N, R
1
=H), (IV-e) (X=N, R
1
=CH
3
) and (IV-f) (X=N, R
1
=CF
3
), depending on the starting materials used, i.e., depending on any one of the reactions of the compound of formula (II-a) or (II-b) with the compound of formula (III-a), (III-b) or (III-c):
Subsequently, the compound of formula (IV) is debenzylated by hydrogenolysis to obtain a phenolic ester compound of formula (V-a):
wherein, X and R
1
has the same meanings as defined previously.
Examples of the compound of formula (V-a) include the compounds of formulas (V-a-1) (X=CH, R
1
=H), (V-a-2) (X=CH, R
1
=CH
3
), (V-a-3) (X=CH, R
1
=CF
3
), (V-a-4) (X=N, R
1
=H), (V-a-5) (X=N, R
1
=CH
3
) and (V-a-6) (X=N, R
1
=CF
3
), which correspond 10 to the compounds of formulas (IV-a) to (IV-f), respectively:
On the other hand, the compound of formula (VI) is inclusive of a compound of formula (VI-a), i.e., the compound of formula (VI) wherein R
3
is H, and a compound of formula (VI-b), i.e., the compound of formula (I) wherein R
3
is CF
3
.
The compound of formula (VI-a) may be prepared by a Grignard reaction, reduction, halogenation and dehalogenation of a halide of R
2
according to a conventional method (Herkes, F. E. et al., J. Org. Chem., 32, 1311(1967); and Nemeth, G. et al., J. fluorine Chem., 76, 91(1996)), as shown in Reaction Scheme E:
wherein, R
2
has the same meaning as defined in formula (I) above; and Z represents Cl or F.
Further, a compound of formula (VI-b) may be prepared by a Grignard reaction and Wittig reaction of a halide of R
2
according to a conventional method (
Choi Gyung Ja
Kim Bum Tae
Kim Jin Cheol
Pak Chwang Siek
Park No Kyun
Anderson Kill & Olick PC
Korea Research Institute of Chemical Technology
Raymond Richard L.
Tucker Zachary C.
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