Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Utility Patent
1998-06-18
2001-01-02
Morris, Patricia L. (Department: 1612)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C514S351000, C546S300000, C546S302000
Utility Patent
active
06169101
ABSTRACT:
The present invention relates to novel nitrogen-containing heterocyclic compounds, to processes for preparing them, to compositions containing them and to methods of using them to combat fungi, especially fungal infections of plants.
More particularly, the invention relates to fungicidal compounds in which a substituted pyridine ring is attached through an oxymethylene linking group to a phenyl ring containing an ortho methyl &bgr;-methoxyacrylate group or methyl &bgr;-methoxyirninoacetate group or an amide derivative thereof.
Fungicidal compounds in which a substituted pyridine ring is linked through an oxymethylene group to a phenyl ring containing an ortho methyl &bgr;-methoxyacrylate group are described in, for example, EP-A-0278595 and EP-A-0350691. Such compounds include those in which the pyridine carries a 6-trifluoromethyl substituent. Similar compounds containing a methyl &bgr;-methoxyiminoacetate group and amide derivatives are described in, for example, EP-A-0363818 and EP-A-0398692. The compounds of the present invention show an unexpected advantage over the known compounds in respect of certain fungicidal properties.
According to the present invention there is provided a compound having the general formula (I):
or a stereoisomer thereof, wherein A is CH or N, X is OCH
3
or NHCH
3
, R
1
is H, chloro or methyl and R
2
is H, fluoro, chloro or methyl.
Of particular interest are compounds where A is N and X is OCH
3
or NHCH
3
and more particularly where A is CH and X is OCH
3
.
Because the carbon-carbon double bond of the group XOC.C═A.OCH
3
is unsymmetrically substituted, the compounds of the invention may be obtained in the form of mixtures of (E)- and (Z)-geometric isomers. However, these mixtures can be separated into individual isomers, and this invention embraces such isomers and mixtures thereof in all proportions. The (E)-isomers with respect to the group XOC.C═A.OCH
3
are usually the more fungicidally active and form a preferred embodiment of the invention.
Further, when R
1
is not the same as R
2
and R
2
is not fluoro, the compounds of the invention may exist in the form of mixtures of optical isomers. However, these mixtures can be separated into the component isomers by known methods and this invention embraces such isomers and mixtures thereof in all proportions.
In one aspect the invention includes a compound of formula (I) or a stereoisomer thereof, wherein A is CH or N, X is OCH
3
or NHCH
3
, R
1
is H, chloro or methyl and R
2
is fluoro or methyl. Suitably, A is N and X is OCH
3
or NHCH
3
. Preferably A is CH and B is OCH
3
.
In another aspect the invention includes a compound having the general formula (I) or a stereoisomer thereof, wherein A is CH or N, X is OCH
3
or NHCH
3
, R1 is H or methyl and R
2
is fluoro or methyl. Suitably, A is N and X is OCH
3
or NHCH
3
. Preferably A is CH and X is OCH
3
.
In yet another aspect the invention includes a compound having the general formula (I) or a stereoisomer thereof, wherein A is CH or N and X is OCH
3
or NHCH
3
, R
1
is H or chloro and R
2
is fluoro or methyl. Suitably, A is N and X is OCH
3
or NHCH
3
. Preferably A is CH and X is OCH
3
.
The present invention is illustrated by compounds of the general formula (II) listed in Tables 1 to 4. Throughout the Tables the W group has the (E)-configuration.
In the compounds of Table 1, W is CH
3
O.CH═C.CO
2
CH
3
.
TABLE 1
(II)
Compound
Compound
No
R
1
R
2
No
R
1
R
2
1
H
H
6
Cl
Cl
2
H
F
7
Cl
CH
3
3
H
Cl
8
CH
3
F
4
H
CH
3
9
CH
3
CH
3
5
Cl
F
Table 2
Table 2 comprises 9 compounds having the same structural formulae and the same values of R
1
and R
2
as the correspondingly numbered compounds in Table 1, but in this case W is CH
3
O.CH═C.CONHCH
3
.
Table 3
Table 3 comprises 9 compounds having the same structural formulae and the same values of R
1
and R
2
as the correspondingly numbered compound in Table 1, but in this case W is CH
3
O.N═CO
2
CH
3
.
Table 4
Table 4 comprises 9 compounds having the same structural formulae and the same values of R
1
and R
2
as the correspondingly numbered compound in Table 1, but in this case W is CH
3
O.N═C.CONHCH
3
.
Table 5
Table 5 shows melting points where measurable or selected proton NMR data obtained at 270 MHz for certain compounds described in Tables 1 to 4. Chemical shifts are measured at 20° C. in ppm from tetramethylsilane and deuterochloroform was used as solvent, unless otherwise stated. The following abbreviations are used:
Compound
Melting
No.
Point
Proton NMR Data (&dgr;)
(Table No.)
° C.
ppm
2(1)
Oil
3.64(3H, s); 3.81(3H, s); 5.29(2H, s); 6.28, 6.49,
6.70(1H, t); 7.1-7.4(4H, m); 7.55(1H, s);
7.56(1H, m); 7.67(1H, t).
2(3)
Oil
3.86(3H, s); 4.03(3H, s); 5.28(2H, s); 6.37, 6.47,
6.68(1H, t); 6.80(1H, d); 7.2-7.6(4H, m);
7.68(1H, t); 7.70(1H, d).
2(4)
68-70
2.91(3H, d); 3.93(3H, s); 5.28(2H, s); 6.29, 6.49,
6.70(1H, t); 6.75(1H, brs); 6.80(1H, d); 7.19(1H,
d); 7.2-7.6(4H, m); 7.68(1H, t).
4(1)
Oil
[1.60(d), 1.68(d) - 3H]; 3.68(3H, s); 3.81(3H, s);
5.25(2H, s); [5.45(q), 5.45(q)-1H]; 6.65(1H, d);
7.01(1H, d); 7.1-7.6(5H, m); 7.57(1H, s).
5(1)
Oil
3.68(3H, s); 3.82(3H, s); 5.33(2H, s); 6.84(1H,
d); 7.1-7.7(6H, m); 7.56(1H, s).
8(1)
Oil
1.94(3H, t); 3.67(3H, s); 3.78(3H, s); 5.30(2H, s);
6.78(1H, d); 7.1-7.7(7H, m); 7.56(1H, s).
9(1)
Oil
1.58(3H, s); 1.68(3H, s); 3.68(3H, s); 3.80(3H, s);
5.25(2H, s); 6.61(1H, d); 7.1-7.6(6H, m);
7.57(1H, s).
s = singlet
d = doublet
t = triplet
q = quartet
m = multiplet
br = broad
ppm = parts per million
The compounds of formula (I) may be prepared by methods well documented in the literature. Suitable methods are disclosed, for example, in EP-A-0278595 and EP-A-0350691, the contents of which are incorporated here by reference.
Thus, compounds of formula (I) may be prepared by reacting the metal salt of a pyridone of formula (III):
wherein R
1
and R
2
are as defined above and M is a metal atom, with a compound of formula (IV):
wherein A and X are as defined above and L is a suitable leaving group.
In practice, a hydroxypyridine of formula (V):
or the tautomeric pyridone is reacted with the compound (IV) in the presence of a suitable base such as silver carbonate in a suitable solvent such as toluene. In this case reaction proceeds via the compound III where M is silver. The leaving group L in the compound (IV) is suitably a halogen, (chloro, iodine or preferably bromine) or OSO
2
CF
3
. Typically, the reactants are refluxed in the toluene solvent for 3-4 hours.
Alternatively, the compounds of formula (I) may be prepared by reacting a pyridine of formula (VI):
wherein R
1
, R
2
and L are as defined above, with the metal salt of a compound of formula (VII):
wherein A, X and M are as defined above. Here the metal atom M is typically an alkali or alkaline earth metal, or it could be another metal such as silver.
Compounds of formula (IV), particularly where L is bromo, are well documented in the literature and can be prepared by the methods described therein; see for example EP-A-0203606 (where A is CH and X is OCH
3
), EP-A-0363818 (where A is N and X is OCH
3
) and EP-A-0398692 (where A is N and X is NHCH
3
). The amides (where X is NHCH
3
) may readily be prepared from the corresponding esters (where X is OCH
3
) by treating the ester with methylamine in a suitable solvent such as methanol.
Compounds of formula (VII) can be prepared by forming the metal salt of the corresponding hydroxymethyl compound using conventional techniques. The hydroxymethyl compounds can be prepared, for example, by the methods described in WO 9307116.
The pyridines of formula (V) and (VI) are either commerically available or can be prepared from commerically available materials by methods described in the chemical literature. A novel method which is particularly convenient for preparing pyridines of formula (V) where R
1
is fluoro and R
2
is H or chloro, and which may be adapted to prepare other pyridines (V) or the tautomeric pyridones, involves the route displayed in S
Morris Patricia L.
Savitsky Thomas R.
Zeneca Limited
LandOfFree
Pyridine derivatives as fungicides does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Pyridine derivatives as fungicides, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Pyridine derivatives as fungicides will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2435314