Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Nitrogen containing other than solely as a nitrogen in an...
Reexamination Certificate
1997-06-16
2003-05-20
Aulakh, Charanjit S. (Department: 1625)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Nitrogen containing other than solely as a nitrogen in an...
C564S183000, C564S161000, C564S166000, C564S176000, C558S014000, C558S017000, C558S392000, C558S415000, C546S316000, C546S317000, C514S514000, C514S522000, C514S619000
Reexamination Certificate
active
06566403
ABSTRACT:
This invention relates to new compositions of N-acetonylbenzamide fungicides, methods of preparing the N-acetonylbenzamides, and their use as fungicides.
N-acetonylbenzamide fungicides are known, see, e. g., U. S. Pat. Nos. 5,254,584 and 5,304,572. One advantage of these known fungicides is that they have high fungicidal activity. Such compounds are particularly advantageous because their high activity allows them to be used at low application rates. However, there is always a need for fungicidal compounds of even higher activity. This results in lower use rates and, therefore, less environmental contamination.
We have discovered that with certain N-acetonylbenzamide fungicides which contain an assymetric carbon atom, the fungicidal activity results primarily from one enantiomer. Thus, fungicidal compositions containing only the active enantiomer provide higher fungicidal activity than compositions containing both enantiomers, when used at the same use rate.
This invention provides compositions, comprising:
a. a compound of formula I, with the stereochemistry depicted:
wherein:
1. A is selected from N and C-R
5
;
2. R
1
and R
2
are different and are independently selected from H, (C
1
-C
6
)alkyl, (C
2
-C
6
)alkenyl, (C
2
-C
6
)alkynyl, and halo(C
1
-C
6
)alkyl and R
2
is stereochemically larger than R
1
;
3. R
3
, R
4
, and R
5
are independently selected from H, halo, (C
1
-C
6
)alkyl, (C
2
-C
6
)alkenyl, (C
2
-C
6
)alkynyl, halo(C
1
-C
6
)alkyl, (Cl-C6)alkoxy, halo(C
1
-C
6
)alkoxy, cyano, nitro, —CR
6
=NOR
7
, —NR
8
R
9
, —CONR
10
R
11
, and —NH—CO—OR
12
wherein R
6
is selected from H, (C
1
-C
6
)alkyl, (C
2
-C6)alkenyl, and (C
2
-C
6
)alkynyl, R
7
is selected from H, (C
1
-C
6
)alkyl, (C
2
-C
6
)alkenyl, (C
2
-C
6
)alkynyl, and (C
1
-C
6
)alkylcarbonyl, R
8
and R
9
are independently selected from H, (C
1
-C
6
)alkyl, and (C
1
-C
6
)alkylcarbonyl, R
10
and R
11
are independently selected from H and (C
1
-C
6
)alkyl; and R
12
is selected from H, (C
1
-C
6
)alkyl, (C
2
-C
6
) alkenyl, and (C
2
-C
6
)alkynyl; and
4. X, Y, and Z are independently selected from H, halo, cyano, thiocyano, isothiocyano, and (C
1
-C
4
)alkylsulfonyloxy; provided that X, Y, and Z are not all H; and
b. an agronomically acceptable carrier;
wherein the composition is predominantly free of the compound of formula I wherein R
1
is stereochemically larger than R
2
;.
The term “halo” means chloro, fluoro, bromo, or iodo. The terms “alkyl” and “alkenyl” include straight-chain, branched-chain, and cycloalkyl and alkenyl groups. The term “alkynyl” includes straight-chain and branched-chain alkynyl groups. The term “alkoxy” includes as the alkyl portion straight-chain, branched-chain, and cyclic alkyl and alkenyl groups. The term “halo” preceeding any one of alkyl, alkenyl, alkynyl, or alkoxy means that one or more of the hydrogens of the group is substituted with a halogen.
The term “stereochemically larger” means the group in question is more space-filling than the group to which it is being compared. When the R
1
and R
2
groups in formula I contain only carbon and hydrogen atoms, since R
2
is the stereochemically larger group, the stereochemistry about the atom to which the R
1
and R
2
groups are attached will take on an “S” configuration. That is, the compound of formula I is designated as the S enantiomer. Throughout this application, the term “S enantiomer” means that the four groups on the carbon to which R
1
and R
2
are attached, when ranked according to the set of sequence rules of the Cahn-Ingold-Prelog system (
Angew. Chem. Int. Ed. Engl.
5, 385-415(1966)), define the carbon as having an S configuration. The term “R enantiomer” means that the four groups form an R configuration. The term “predominantly free” means that the ratio of enantiomers is greater than 3:1, preferably greater than 5:1, more preferably greater than 10:1, and most preferably greater than 100:1.
Because of their high fungicidal activity preferred compounds are those of formula I wherein: R
3
is selected from halo, cyano, nitro, and —CH=NOCH3; R
4
is selected from H, halo, cyano, (C
1
-C
6
)alkyl,
13
NH—CO—OR
12
,and —NR
10
R
11
; R
5
is selected from halo, cyano, and (C
1
-C
6
)alkyl; R
1
and R
2
are independently selected from (C
1
-C
6
)alkyl; X and Y are H; and Z is chloro.
Because of their outstanding fungicidal activity and selectivity the most preferred compounds of formula I are those wherein: R
3
is selected from chloro, bromo, CN, and —CH=NOCH3; R
4
is selected from H, —NH2, CN, and —CH3; R
5
is selected from chloro, bromo, CN, and —CH3; R
1
is methyl; R
2
is ethyl; X and Y are H; and Z is chloro.
This invention also provides fungicidal compounds of formula I.
In addition, this invention provides a process for preparing compounds of formula I, comprising the steps of:
a. reacting a protonated amino acid ester of the formula:
wherein R
1
and R
2
are different and are independently selected from H, (C
1
-C
6
)alkyl, (C
2
-C
6
)alkenyl, (C
2
-C
6
)alkynyl, and halo(C
1
-C
6
)alkyl and R
2
is stereochemically larger than R
1
,and R is selected from (C
1
-C
6
)alkyl, with an acyl chloride of the formula:
wherein A is selected from N and C-R
5
and R
3
, R
4
, and R
5
are independently selected from H, halo, (C
1
-C
6
)alkyl, (C
2
-C
6
)alkenyl, (C
2
-C
6
)alkynyl, halo(C
1
-C
6
)alkyl, (C 1-C6)alkoxy, halo(C
1
-C
6
)alkoxy, cyano, nitro, —CR
6
=NOR
7
, —NR
8
R
9
, —CONR
10
R
1
1, and —NH-CO-OR
12
wherein R
6
is selected from H, (C
1
-C
6
)alkyl, (C
2
-C
6
)alkenyl, and (C
2
-C
6
)alkynyl, R
7
is selected from H, (C
1
-C
6
)alkyl, (C
2
-C
6
)alkenyl, (C
2
-C
6
)alkynyl, and (C
1
-C
6
)alkylcarbonyl, R
8
and R
9
are independently selected from H, (C
1
-C
6
)alkyl, and (C
1
-C
6
)alkylcarbonyl, R
10
and R
11
are independently selected from H and (C
1
-C
6
)alkyl; and R
12
is selected from H, (C
1
-C
6
)alkyl, (C
2
-C
6
)alkenyl, and (C
2
-C
6
)alkynyl; to produce a benzamide-ester of the formula:
b. hydrolyzing the ester moiety of the benzamide-ester to produce a benzamide-acid of the formula:
c. cyclizing the benzamide-acid to produce an oxazolinone of the formula:
d. forming the c ompound of formula I by ring opening the oxazolinone.
The protonated amino acid ester may be prepared using standard esterification procedures such as treatment of the corresponding amino acid with an alcohol under acidic conditions. We have found that methanol is the preferred alcohol because of the ease of removal of a methyl group during the hydrolyzing step.
In a similar manner, the hydrolyzing step is conducted using standard conditions. Base catalyzed hydrolysis using sodium hydroxide as the base is preferred. The only limitations to the reaction conditions used in the hydrolyzing step are that the conditions must be sufficiently selective so that the ester bond is hydrolyzed but the amide bond is not. Strong base catalysts must be avoided when R
1
or R
2
is hydrogen to eliminate side reactions resulting from abstraction of the hydrogens.
The oxazolinone is produced in the cyclization step by dehydration of the benzamide-acid. Such dehydrations may be conducted using a variety of dehydrating agents such as acetic anhydride at elevated temperatures (90°-100° C.) phosphorous oxychloride, phosphorous pentachloride, and ethyl hloroformate/triethylamine. Mild dehydrating agents such as acetic anhydride are preferred because they are easily removed and side reactions are avoided.
Ring opening of the oxazolinone to form the compound of formula I may be conducted in a single or in multiple steps. An example of a single step ring opening is treating the oxazolinone with chloromethyllithium which produces the compound of formula I wherein X and Y are H and Z is Cl. An example of a multiple step ring opening is treating the oxazolinone first with methyllithium to form the compound of formula I wherein X, Y, and Z are all H, chlorinating the ketone to produce a mixture of compounds of formula I wherein one or two of X, Y, and Z are Cl and the remaining are H, followed by selec
McLaughlin Thomas Anthony
Michelotti Enrique Luis
Young David Hamilton
Aulakh Charanjit S.
Dow AgroSciences LLC
Rogerson Thomas D.
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